UEG Week 2015 Poster Presentations

MONDAY, OCTOBER 26, 2015   09:00-17:00

LIVER & BILIARY I – HALL 7__________

P0001 SYSTEMIC ADMINISTRATION OF XENOGENIC HUMAN ADIPOSE-DERIVED STROMAL CELLS COMBINED WITH ADENOVIRUS-HUPA IMPROVES EXPERIMENTAL LIVER FIBROSIS

A. Meza-Rios¹, J. Armendariz-Borunda^1,2, L. Garcia-Benavides³, J. Garcia-Bañuelos¹, A. Salazar-Montes¹, A. Sandoval-Rodriguez¹

¹Institute for Molecular Biology and Gene Therapy, University of Guadalajara, ²Innovare, ³Unit of Cardiovascular Investigation, University of Guadalajara, Guadalajara, Mexico

Contact E-mail Address: anasol44@hotmail.com

Introduction: In animal models of liver fibrosis transplant of hADSCs (adipose-derived stromal cells) improved hepatic function and reduced fibrotic tissue. Besides, systemic administration of Ad-huPA diminished liver fibrosis and increased tissue regeneration.

Aims & Methods: The aim of this study was to evaluate if the simultaneous administration of both therapies shows an enhanced antifibrogenic effect in cirrhotic rats. ADSCs were isolated from human fat tissue, expanded and characterized by expression of cellular markers (CD105⁺, CD73⁺, HLA-ABC⁺, CD45, CD34^-,HLA-DRII^-) and cell differentiation to osteogenic, adipogenic and hepatogenic linage. Ad5-huPA vector was generated under CMV promoter control. CCl₄-cirrhotic rats via ileac vein were administered with 2X × 10⁶ cells/rat hADSCs or 3x10¹¹ vp/rat Ad-huPA or both therapies. One day before treatment, all animals begin immunosuppression with 10mg/kg/day of Cyclosporine A until sacrifice 10 days later. Fibrotic tissue, Collagen fibers and α-SMA immunoreactivity as well as expression of TGF-β1, collagen α1, CTGF, PAI-I and α-SMA were evaluated. Also, serum levels of ALT, AST and albumin, biodistribution of hADSCs and liver levels of huPA protein were examined.

Results: Administration of hADSCs, Ad-huPA and Ad-huPA/hADSCs reduces (p < 0.01) liver fibrosis in 78.9%, 65.2% and 72% respectively, compared to cirrhotic controls and diminishes Collagen α1, CTGF and α-SMA mRNA liver levels (p < 0.05). Furthermore, TGF-β1 and PAI-I liver mRNA levels (p < 0.05) decreases in animals treated with Ad-huPA and hADSCs. ALT and AST serum levels showed a significant decrease in hADSCs group (p < 0.05). Serum levels of albumin increased in the Ad-huPA, hADSCs and Ad-huPA/hADSCs groups (p < 0.05) compared with control group. hADSCs, Ad-huPA and hADSC/Ad-huPA administration reduced 4.3, 2.4 and 2.7 fold respectively (p ≤ 0.001) collagen staining, compared to cirrhotic controls. hADSCs were mainly detected in liver and few of them in lung and spleen. huPA protein was expressed in similar levels in liver homogenates of Ad-huPA and Ad-huPA/hADSCs groups.

Conclusion: The combination of Ad-huPA and hADSCs reduced liver fibrosis and expression of pro-fibrogenic molecules in CCl_4-cirrhotic animals; however, it does not improve antifibrogenic effects of individual treatments.

Disclosure of Interest: None declared

P0002 THE DIAGNOSTIC PERFORMANCE OF NON-INVASIVE SERUM MARKERS TO IDENTIFY SIGNIFICANT LIVER FIBROSIS IN PATIENTS WITH PRIMARY BILIARY CIRRHOSIS AND PRIMARY SCLEROSING CHOLANGITIS

A. Sheptulina¹, E. Shirokova¹, V. Ivashkin¹

¹First Moscow State Medical University n.a. I.M. Sechenov, Moscow, Russian Federation

Contact E-mail Address: sheptulina.anna@gmail.com

Introduction: Development of models and indexes incorporating non-invasive markers of liver fibrosis in chronic cholestatic liver diseases, namely primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), is essential to facilitate the assessment of liver fibrosis progression and the effectiveness of new therapies.

Aims & Methods: The aim of this study was to evaluate the ability of indirect serum markers for discriminating between mild and significant fibrosis in patients with PBC and PSC. Data from 82 patients with PBC and 22 patients with PSC were analyzed retrospectively (admitted between 2008 and 2014). Forns index, Fibrosis 4 score (FIB4), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) (AST/ALT) ratio index, AST to the platelet ratio index (APRI) and platelet count/spleen diameter ratio index were calculated based on results of blood analyses and abdominal ultrasound. Results of the histological study of the liver with the histology activity index (according the Knodell score) and stage of fibrosis assessment (according the METAVIR score) were used as a reference method and were available for all included patients. Receiver operating characteristic curve (ROC) analysis was conducted to determine diagnostic performance of these indexes for identification of significant liver fibrosis in patients with PBC and PSC.

Results: Among all the patients with PBC (n=82; median age [25th – 75th interquartile range] 54.5 years [48.75-60.25]; 95.12% were female) 52.4% (n=43) had significant fibrosis (F ≥2) and 23.17% (n=19) had cirrhosis. In PSC group (n=22; median age 38 years [26.5-48.5]; 27.2% were female) 50% (n=11) and 31.8% (n=7) of patients had significant fibrosis (F ≥2) and cirrhosis, consequently. Platelet count/spleen diameter ratio index (AUROC=0.761) was superior to APRI, AST/ALT ratio index, FIB4, and Forns index at distinguishing between mild and significant fibrosis in patients with PBC. With a cut-off of >19.8, the presence of significant fibrosis could be excluded with a 74.4% negative predictive value (NPV) and 78% specificity. In patients with PSC FIB4 index (AUROC=0.843), platelet count/spleen diameter ratio index (AUROC=0.752), and APRI (AUROC=0.744) were superior to Forns index and AST/ALT ratio index at distinguishing between mild and significant fibrosis. With a FIB4 index cut-off value of <0.76, the presence of significant fibrosis could be excluded with a 85.7% NPV and 90.9% specificity.

Conclusion: Application of platelet count/spleen diameter ratio index in patients with PBC enabled correct classification of 74% of patients included in this study. Overall 73% of patients with PSC could be correctly classified by using FIB4 index. Thus, application of tests, incorporating indirect serum markers of live fibrosis, could help to decrease the need for liver biopsy in these patients.

Disclosure of Interest: None declared

P0003 EXPRESSION ANALYSIS OF PLASMA APOLIPOPROTEINS IN HEPATOCELLULAR CARCINOMA: A PROTEIN-BASED HCC-ASSOCIATED STUDY

D. Bharali¹, P. C. Ray¹, P. Kar¹

¹Medicine, Maulana Azad Medical College, New Delhi, India

Contact E-mail Address: dipubhli@gmail.com

Introduction: Hepatocellular carcinoma (HCC) is the 6th cancer in incidence worldwide and the 3rd leading cause of cancer death. We aimed to identify new markers of HCC using a protein-based analysis.

Aims & Methods: To find out differential expression of apolipoproteins- ApoA1 and ApoAIV in HCC and controls without HCC. 30 Patients with HCC and 30 liver cirrhosis were included in the study. Target apolipoproteins were separated by SDS PAGE from blood plasma and the expression changes of ApoA1 and ApoA4 were confirmed by Western blotting followed by densitometric protein semiquantitaion estimation along with ELISA-based protein quantification.

Results: Western blotting densitometry image analysis of the plasma samples following CDC protocol and the comparison between patients with and without HCC revealed differential expression of ApoA1 and ApoA4. Levels of Apo-A4 were significantly higher in patients of liver cirrhosis and chronic hepatitis without HCC than in patients with HCC (0.208 ± 0.07 & 0.119±.016 _VS 0.119 ± 0.005; P < 0.01). Levels of Apo-A1 were significantly higher in patients with HCC than in controls without HCC (0.279 ± 0.003 _VS 0.171 ± 0.034 & 0.199±.014; P < 0.01).

Apo-A1 and ApoA4 were further tested whether quantitative measurement could be utilized as a diagnostic tool to distinguish patients with HCC from the controls without HCC by ELISA. Once calibration curves were proven to be analytically optimal, Apo-A1, ApoA4 and AFP were measured in blood plasma samples by ELISA according to the manufacturer’s protocol. The result showed significant increased Apo-A1 expression in HCC group (P <0.01).

Mean ApoA1 concentration in human blood plasma: HCC- 81726.61 ng/ml; LC- 16388.09 ng/ml; chronic hepatitis – 22172.30 ng/ml; Mean ApoA4 concentration in human blood plasma: HCC-307.79 ng/ml; LC- 614.86 ng/ml; chronic hepatitis – 495.13 ng/ml. ELISA Assays revealed that there was a deregulation in expression of both ApoA1 and ApoA4 proteins deflected from the normal levels in healthy controls. It showed that the plasma levels of ApoA1 were higher in HCC than both the healthy and disease controls. On the other hand plasma levels of ApoA4 were lower in HCC than controls with liver cirrhosis and chronic hepatitis but without HCC. Plasma levels of ApoA4 were significantly higher in liver cirrhosis than that of HCC as well as healthy control. Plasma levels of AFP were higher in HCC than that of healthy control and liver cirrhosis along with chronic hepatitis.

Conclusion: Apolipoprotein A1 is highly expressed in HCC in comparison to cirrhosis and may be used as future diagnostic tool in addition and associated with other conventional biomarkers for HCC after further analysis of a higher number of population.

Disclosure of Interest: None declared

P0004 RIFAXIMIN PREVENTS THE DEVELOPMENT OF STEATOHEPATITIS BY INHIBITING NF-KB AND TNF ALPHA IN RATS FED WITH HIGH FRUCTOSE

N. Cabuk Celık¹, I. H. Bahcecioglu², M. Ispiroglu², M. Tuzcu³, I. H. Ozercan⁴, N. Ilhan⁵, K. Sahın⁶

¹Internal Medıcıne, ²Gastroenterology, Firat University, faculty of Medicine, ³Biology, Firat University Faculty of Science, ⁴Pathology, ⁵Biochemistry, Firat University, faculty of Medicine, ⁶Animal nutrition, Firat University, Faculty of Veterinary, Elazig, Turkey

Contact E-mail Address: ihbahcecioglu@yahoo.com

Introduction: Non alcoholic fatty liver disease is the most common liver disease in the world. In addition it is commonly associated with the methabolic syndrome. There is possibility that the disease may be associated with the increase fructose consumption

Aims & Methods: In this study, we investigated the preventive effect of rifaximin in steatohepatitis induced by fructose in rats. In this study, 42 male Sprague-Dawley rats were divided in 6 groups with an equal number. Normal diet was given to Group 1. Fructose was given to Group 2, fructose + rifaximin once a week was given to Group 3, fructose + rifaximin three days a week was given to Group 4, normal diet + rifaximin once a week was given to Group 5 and normal diet + rifaximin three days a week was given to Group 6. Rifaximin was administered at a dose of 15 mg/kg by orogastric catheter. 50% fructose was added to drinking water. The rats were decapitated at the end of 8 weeks. At the end of 8 weeks, hepatic tissue samples were obtained from the rats for histopathological examination and MDA, TNF-α, NF-kB, Nrf-2 and HO-1 levels. Biochemical examination was performed and plasma glutathione peroxidase, TNF-α, 4-hydroxynonenal levels were measured.

Results: The body and liver weights were increased in all rats fed with fructose compared to the control group. On histopathological examination, balloning degeneration, inflammation and grade 1 steatosis developed in the rats who were given 50% fructose. Steatosis Grade 2 and above and fibrosis was not found in any rat. Ballooning degeneration and inflammation were found with a significantly lower rate in rates who received rifaximin. No significant difference was found between different doses of rifaximin. Plasma and tissue TNF-α levels and NF-κB were found to be significantly lower in the groups who received rifaximin compared to the group who received fructose. In addition, GSH-Px, Nrf-2, HO-1 levels were found to be high in the group who received rifaximin. No significant difference was found between different doses of rifaximin.

Conclusion: Rifaximin protects aganist steatosis, ballooning degeneration and inflammation induced by high fructose diet in rats. It was thought that rifaximin may be prevent the steatohepatitis inhibiting NF-kB, TNF-α, with decreasing intestinal translocation of endotoxin. New studies on this subject are needed.

Disclosure of Interest: None declared

P0005 CELECOXIB AMELIORATES INTESTINAL INFLAMMATORY INFILTRATION ALONG THE GUT-LIVER AXIS VIA RESTORATION OF INTESTINAL EPITHELIAL BARRIER IN CIRRHOTIC RAT

J.-H. Gao¹, Z.-Y. Huang¹, C.-W. Tang¹

¹Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China

Contact E-mail Address: 272303614@qq.com

Introduction: Liver cirrhosis is an inevitable outcome triggered by chronic inflammation. However, the mechanism of inflammatory infiltration in the liver is largely unknown. It is accepted that intestinal epithelial barrier dysfunction might contribute to liver cirrhosis by facilitation of inflammatory infiltration along the gut-liver axis. In the present study, we characterize the effects of celecoxib on inflammatory infiltration and intestinal epithelial barrier of cirrhotic rats.

Aims & Methods: Liver cirrhosis was induced by peritoneal injection (i.p.) of thiacetamide (TAA, 200 mg/kg every 3 days for 16 weeks). 36 male Sprague-Dawley rats were randomized into control, TAA and TAA + celecoxib groups with 12 animals in each group. TAA + celecoxib group received TAA plus celecoxib (20mg/kg/day) from the initiation of TAA administration. TAA group received TAA plus placebo and control group received normal saline (i.p.). The parameters for fibrosis (Collagen III and a-SMA), inflammatory infiltration (TNF-α, IL-6, and CD3/CD4/CD8 lymphocytes), barrier function (ZO-1, claudin-4 and E-cadherin) and integrated signal pathways (cyclooxygenase-2 (COX-2), p-Akt, p-ERK and NF-kB) were determined. Moreover, the content of TNF-α, IL-6 and lipopolysaccharide (LPS) was quantified. In vitro, human colorectal adenocarcinoma cells Caco-2 was treatment with vehicle, celecoxib, PGE2, PGE2 antagonist, EP-2 antagonist, ERK inhibitor and Akt inhibitor, respectively. Afterwards, ZO-1, claudin-4 and E-cadherin, Akt/p-Akt and ERK/p-ERK were evaluated by immunocytofluorescence and Western blot.

Results: In vivo, compared with TAA group, fibrotic areas and Ishak’s scoring in TAA + celecoxib group were remarkably decreased by 40.4% and 36.1%. The mRNA levels of a-SMA and collagen III in TAA + celecoxib group were also reduced. Moreover, hepatic and intestinal inflammatory infiltration, which express as increased mRNA and protein level of TNF-α, IL-6, LPS and decreased portal venous CD3+, CD3+/CD4+, CD3+/CD8+ and CD3+/CD4+/CD8+ T cell, were observed in TAA group when compared with those in control group. Interestingly, the hepatic and intestinal inflammatory infiltration was attenuated after treatment with celecoxib. Disruption of intestinal barriers that induced by TAA, which was verified by ultrastructure and decreased mRNA and protein of junction molecular (ZO-1, Cluadin-4 and E-cadherin), was partly restored after treatment with celecoxib. Moreover, activation of p-Akt, p-ERK and NF-kB in TAA group was significantly inhibited by celecoxib treatment. In vitro, compared with vehicle treated Caco-2 cells, the protein levels of ZO-1, Cluadin-4, E-cadherin were obviously increased by celecoxib, PGE2 antagonist, EP-2 antagonist and ERK inhibitor treatment but not by Akt inhibitor.

Conclusion: Long-term treatment with celecoxib attenuates liver cirrhosis via blockage of inflammatory infiltration along the gut-liver axis and restoration of intestinal epithelial barrier. This effect afforded by celecoxib may attribute to its modulation on COX-2 – PGE2 – p-ERK integrated signal pathways. Our results suggest that celecoxib might be considered as a potential therapeutic agent in the preventive strategy for the patients suffering from liver cirrhosis.

Disclosure of Interest: None declared

P0006 EFFECTS OF URSODEOXYCHOLIC-ACID AND RIFAMPICIN ON AUTOPHAGY IN THE LIVER

K. Panzitt¹, H.-U. Marschall², P. Fickert¹, M. Trauner³, M. Wagner¹

¹Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria, ²Department of Molecular and Clinical Medicine, Su sahlgrenska, Gothenborg, Sweden, ³Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria

Contact E-mail Address: katrin.panzitt@medunigraz.at

Introduction: Bile acids and activation of the bile acid receptor FXR inhibit autophagy, a cellular self-digestion process necessary for cell homeostasis and regeneration. The effects of chronic bile acid accumulation in chronic cholestatic liver disease on autophagy have not been studied in detail. However, indirect evidence (e.g. accumulation of Mallory-Denk bodies in primary biliary cirrhosis) indicate that autophagy may be impaired in human cholestasis.

Aims & Methods: We aim to determine whether ursodeoxycholic-acid (UDCA) and Rifampicin (Rifa), two drugs for the treatment of human cholestatic liver disease, may activate autophagy as a potential mode of drug action.

Markers of autophagy (LC3, p62, ATG5, 7, 12) and the upstream mTOR signaling pathway (Raptor, ULK1, pS6K) have been studied by Western blot and immunofluorescence in liver biopsy from patients treated with UDCA and Rifampicin. Mechanistic details of UDCA and Rifa action have further been studied in human HepG2 cells and primary hepatocytes.

Results: Both UDCA and Rifampicin induce LC3 as the main autophagy readout in human biopsies. UDCA activates autophagy via mTOR-ULK1 signaling whereas Rifampicin induces autophagy on transcriptional levels (LC3C, LAMP1, ATG10) without impacting on mTOR signaling. Knockdown of the Rifampicin activated transcription factor PXR significantly represses autophagy already under basal conditions on mRNA and protein levels. In addition, PXR knockdown prevents Rifampicin induced autophagy induction.

Conclusion: UDCA and Rifampicin induce autophagy in the liver via different mechanisms. UDCA induces autophagy via mTOR signaling pathways and Rifampicin induces autophagy mTOR independently via the transcription factor PXR. Part of the beneficial effects of UDCA and Rifampicin in the treatment of cholestatic liver disease may be attributed to an induction of autophagy. Both compounds, UDCA and Rifampicin may have additional beneficial effect by inducing autophagy on other hepatological as well as non-hepatological diseases.

Disclosure of Interest: None declared

P0007 INDUCTION OF CB2 EXPRESSION, HSC APOPTOSIS AND CB1 INHIBITION BY QUERCETIN ADMINISTRATION IN AN ANIMAL MODEL OF LIVER FIBROSIS

A. Salazar Montes¹, L. D. Hernández Ortega¹, A. A. Sobrevilla Navarro¹, J. Armendariz Borunda¹, on behalf of Universidad de Guadalajara

¹Molecular Biology and Genomics, Universidad de Guadalajara, Guadalajara, Mexico

Contact E-mail Address: drldortega@gmail.com

Introduction: Cirrhosis is a distortion of normal tissue architecture which develops when the liver is chronically damaged. Activated hepatic stellate cells (HSC) participate actively in liver fibrosis development where endocanabinoids receptors CB1 and CB2 regulate this process. Quercetin, a flavonoid with antioxidant properties has shown prevent liver fibrosis.

Aims & Methods

Aim: To elucidate the effect of quercetin on CB1 and CB2 expression and on HSC activation in an experimental model of cirrhosis.

Methods: Wistar rats were intoxicated with CCl₄ for eight weeks and concomitantly treated with quercetin (150mg/Kg/day). Animals were sacrificed, livers were taken for histology (Masson, Sirious red, immunohistochemistry (IHC) for a-sma and TUNEL for apoptosis), for gene expression (Col-1 TGF-b, CTGF, CB1 and CB2) and for western blot (CB1 and CB2).

Results: Expression of Col-1, TGF-b1 and CTGF significantly increased in CCl₄ cirrhotic rats compared to healthy rats. Tretament with quercetin significantly decreased expression of all these genes. Liver fibrotic rats presented a fibrosis index of 22.5% while rats with quercetin treatment had a fibrosis index of 10.76%. Activated HSC determined by IHC for a-sma and quantity of apoptotic cells were 40% less and 17 times more respectively in quercetin group respect to control. CB1 expression was 20% decreased where CB2 was 47% increased with quercetin treatment respect to group without quercetin treatment.

Conclusion: Quercetin administration prevents liver injury in an animal model of cirrhosis increasing CB2 expression and reducing CB1 expression. In the same way, quercetin promotes HSC apoptosis decreasing activated hepatic stellate cells number.

Disclosure of Interest: None declared

P0008 THE LEVEL OF TGF-β1 AND TIMP-1 IN PATIENTS WITH LIVER CIRRHOSIS

O. Shapoval¹, R. Yatsyshyn¹, V. Vyshyvanyuk¹, I. Popadynets¹, V. Petryna¹, O. Babenko¹, N. Skrobach¹

¹Internal Medicine #1, Clinical Immunology and Allergology, Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine

Contact E-mail Address: oshapoval@rambler.ru

Introduction: As chronic liver disease progresses, an imbalance between synthesis and breakdown of extracellular matrix (ECM) occurs. Matrix metalloproteinases (MMPs) are involved in ECM degrading while tissue inhibitors of metalloproteinases (TIMPs) prevent their fibrolytic action. Circulating levels of tissue inhibitor of metalloproteinase (TIMP)-1 was investigated as parameters for the diagnosis of fibrosis in chronic liver disease. Removal of excess collagen after cessation of liver injury is regulated by TIMP-1 and TGF-β1 (transforming growth factor-β1). Among growth factors, TGF-β1 appears to be a key mediator in human fibrogenesis.

Aims & Methods: The aim of research was to assess the level of TGF-β1 and TIMP-1 in patients with liver cirrhosis (LC).

Materials and methods: 80 patients with LC of nonviral etiology were examined. Classification of the International Working Group and the World Congress of Gastroenterology (Los Angeles, 1994) was used for the diagnosis of LC. Diagnosis was based on anamnestic, clinical and laboratory data, ultrasound evidence of liver damage, detection and absence of serological markers of viral hepatitis and alcoholic origin of the disease. Parameters of free-radical oxidation and antioxidant system (malonaldehyde, diene conjugates, the activity of ceruloplasmin, transferrin saturation with iron) and medium molecular weight peptides as manifestation of endogenous intoxication were determined in the patients’ the blood. For all patients ¹³C-metacetin breath test was performed to assess the functional capacity of hepatocytes. TIMP-1, TGF-β1 and bacterial endotoxin were determined with the ELISA method. The investigated group included the patients with LC at stage A and B according to Child-Pugh.

Results: Examined patients included 71 men (88.7%) and 9 women (11.3%). Age of patients ranged from 34 to 64 years on average (47.7 ± 0.82) years. Disease duration in patients ranged from 2 to 9 years.

The level of TIMP-1 in patients with LC was (523.5 ± 6.5) pg/ml and significantly different from healthy persons - (164.6 ± 8.50) pg/ml (p < 0.05). TGF-β1 levels in patients with LC was 437.7 ± 5.9 pg/ml and 166.98 ± 6.73 pg/ml (p < 0.05) in healthy persons. The level of bacterial endotoxin in patients with LC was 79.32 ± 2.1 pg/ml and significantly different from healthy persons – 23.6± 0.91 pg/ml (p < 0.05). Endotoxin was positively correlated with TGF-β1 (r=0.338, P <0.05), and positively correlated with medium molecular weight peptides (r=0.413, P <0.05).

Conclusion: Cytokines are released under the influence of bacterial endotoxin from Kupffer cells causing the production of fibrogenic factors (such as TGF-β1), and leading to stimulation of fibrogenesis and progression of disease.

Disclosure of Interest: None declared

P0009 ADMINISTRATION OF ANTISENSE OLIGODEOXYNUCLEOTIDES TO NERVE GROWTH FACTOR ATTENUATES INFLAMMATION AND LIVER DAMAGE IN ACUTE LIVER DAMAGE MODELS

R. Bruck¹, E. Hubel¹, I. Zvibel¹

¹Gastroenterology, Tel Aviv Medical Center, Tel Aviv, Israel

Contact E-mail Address: rafib@tlvmc.gov.il

Introduction: Nerve growth factor (NGF) has pro-inflammatory effects in lung and skin inflammatory diseases. During liver regeneration, NGF secreted by hepatocytes induces hepatic stellate cell apoptosis. However, NGF involvement in models of liver damage and inflammation has not yet been assessed.

Aims & Methods

Aim: We investigated the possible inflammatory effects of NGF on isolated hepatic stellate cells (HSC), as well as the in vivo effect of silencing NGF on acute liver damage and inflammation.

Methods: Primary HSC from rats and mice were isolated and cultured for 7d and 14d to obtain activated and fully activated HSC, respectively. HSC were treated with 100ng/ml NGF and proNGF and inflammatory cytokine expression was assessed by qRT-PCR and ELISA. Acute liver damage was induced by two i.p. injections of CCl₄ (1ml/g body weight) or by bile duct ligation (BDL) and mice received daily treatment with antisense oligodeoxynucleotide to NGF (ODN)(25mg/kg body weight).

Results: Both NGF and proNGF induced expression of pro-inflammatory cytokines TNFa and IL-6 in activated and fully activated primary rat and murine HSC. Administration of antisense ODN to NGF in the acute CCl₄ and BDL models reduced liver damage, as demonstrated by significantly reduced serum liver enzymes. In addition, antisense ODN to NGF resulted in dramatically reduced (6- fold) hepatic mRNA expression of pro-inflammatory cytokines IL-6, TNFa and MCP1 in the acute CCl₄ acute model. In the BDL-induced acute liver injury, administration of ODN resulted in a two-fold reduction in TNFa, MCP-1 and CXCL1expression.

Conclusion: Silencing NGF may have a beneficial, anti-inflammatory and protective effect in acute hepatotoxicity models.

Disclosure of Interest: None declared

P0010 FERMENTED SOYMILK PREVENTS FREE FATTY ACID-INDUCED LIPOGENESIS AND PRODUCTION OF REACTIVE OXYGEN SPECIES IN HEPATOCELLULAR STEATOSIS MODEL

S. B. Ahn¹, B. K. Son¹, Y. S. Park¹, Y. J. Jo¹, S. H. Kim¹, Y. K. Jo¹

¹Dept of Gastroenterology, Eulji University, College of Medicine, Seoul, Republic of Korea

Contact E-mail Address: dr486@hanmail.net

Introduction: Ingredients of soy and fermented products have been widely utilized as food supplement for health-enhancing properties, such as reducing the risk of osteoporosis, protection from cardiovascular diseases, and prevention of prostate and breast cancer. This study was carried out to examine the effects of fermented soymilk (FSM) on the free fatty acid-induced lipogenesis in an in vitro model of hepatocellular steatosis model.

Aims & Methods: HepG2 cells were incubated with 0.2 mM of palmitic acid (PA) for 24 h to induce lipogenesis and to accumulate the intracellular lipid accumulation, which was observed by oil red O and Nile red staining. The PA-treated cells were co-incubated with 0.04∼1.0% of lyophilized FSM, 0.05 mM of genistein, and 50 nM of estrogen, respectively. Western blot analysis of sterol regulatory element-binding protein-1 (SREBP-1) and nuclear factor erythroid 2-related factor-2 (NRF-2) were performed to examine the lipogenesis related extracellular signal-regulated kinase (ERK) pathway. Cellular reactive oxygen species (ROS) was measured by the DCFDA assay kit.

Results: Lipid accumulations in the PA and FSM co-incubated cells were significantly decreased by 0.5% and 1.0% of FSM without cytotoxicity. Treatments of PA and combining with genistein and estrogen significantly increased the expressions of SREBP-1. However, FSM co-incubation significantly attenuated the expression of SREBP-1 in the PA treated cells. In addition, expression of NRF-2 and phosphorylation of ERK were significantly increased in the PA and FSM co-incubated cells. PA-induced ROS production was significantly reduced by 1.0% of FSM. Meanwhile, genistein or estrogen alone did not lead to significant differences in ROS production.

Conclusion: Our results show that bioactive components, except genistein and phytoestrogen, in fermented soymilk protect hepatocytes against lipid accumulation and ROS production induced by free fatty acid. These effects may be mediated by inhibition of SREBP-1 and activation of NFR-2 via ERK pathway in hepatocytes.

Disclosure of Interest: None declared

P0011 NOD2 MUTATIONS AND ALCOHOLIC LIVER CIRRHOSIS: IS THERE A LINK?

S. M. D. Giestas¹, J. Carvalheiro¹, A. Oliveira¹, R. Cardoso¹, M. M. Donato², S. Lopes¹, P. Figueiredo¹, D. Gomes¹, L. Tomé¹, C. Agostinho¹, P. Freire¹, C. Sofia¹

¹Gastroenterology, Centro Hospitalar e Universitário de Coimbra, ²Center of Gastroenterology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

Contact E-mail Address: silviagiestas@gmail.com

Introduction: Classically linked with increased risk of Crohn's disease, the polymorphisms of the NOD2, a gene involved in the immune response regulation, have been associated, more recently, with a higher risk of some infections and neoplasms. In liver cirrhosis, carriers of NOD2 variants have been related with an increase in the risk of spontaneous bacterial peritonitis (SBP) because of impaired intestinal mucosa barrier function.

Aims & Methods: The aim of this study was to assess whether NOD2 mutations are risk factors for alcoholic liver cirrhosis (ALC) and whether there are genotype-phenotype correlations in these patients.

Methods: Case-control study involving the research of the 3 main NOD2 mutations (3020insC, R702W e G908R) in 202 patients with ALC and in 202 healthy controls.

Results: NOD2 mutations were found in 43 patients (21.3%) and in 27 controls (13.4%) (p=0.064). The mean age of patients was 59.3 ± 12.6 years old and 79.8% were males. The average age at diagnosis of ALC was significantly lower in patients with mutation (48.3 ± 11.8 vs. 58.2 ± 12.4 years old; p=0.008). The incidence of NOD2 mutations, especially of the R702W variant, was significantly higher in patients with SBP (38.0% vs 13.7%; p=0.022). No significant associations were detected between NOD2 mutations and hepatocellular carcinoma (22.2% vs 19.7%, p=0.603), hepatorenal syndrome (28.5% vs 19.7%, p=0.454), hepatic encephalopathy (22.5% vs 20.0%, p=0.727), gastroesophageal variceal bleeding (17.6% vs 23.1%, p=0.775), acute alcoholic hepatitis (31.2% vs 20.4%, p=0.403) or other infectious intercurrences (18.7% vs 22.9%, p=0.674).

Conclusion: In this study, the NOD2 mutations are associated with a trend for increased risk of ALC, earlier onset of the disease and showed to be a risk factor for PBE.

Disclosure of Interest: None declared

P0012 HEPATIC EXPRESSION OF SOMATOSTATIN RECEPTOR 2 MAY BE REGULATED BY CYCLOOXYGENASE-2 IN RAT MODEL OF LIVER CIRRHOSIS

Y. Lu¹, J. Gao¹, S. Wen¹, C. Tang¹

¹West China Hospital, Sichuan University, Chengdu, China

Contact E-mail Address: luyaoyao512@163.com

Introduction: Somatostatin has been used in liver cirrhosis for several decades. Its effects are mediated through binding to its 5 receptors, somatostatin receptor 1-5 (SSTR1-5), among which SSTR2 takes part in an interesting physiopathological process. Hepatic expression of Somatostatin receptor 2 (SSTR2) is upregulated in liver cirrhosis. However, its regulatory mechanism during liver cirrhosis remains obscure.

Aims & Methods: The present study aimed to examine the mechanisms of SSTR2 regulation in liver tissue during the development of liver cirrhosis. Eighteen rats were randomly assigned into control group, cirrhosis group and cirrhosis + celecoxib group, with 6 in each group. Liver cirrhosis was induced in rats by injection of thioacetamide (TAA) introperitoneally. Expressions of SSTR2, Cyclooxygenase -2 (COX-2) were assessed by western blot and real-time PCR. DNA methylation level of SSTR2 was investigated by bisulfite sequencing. To explore possible regulation effect of COX-2 on the expression of SSTR2, COX-2 was induced in L02 cell lines by transfection of COX-2 and addition of TAA with final concentration from 20mg/L to 80mg/L.

Results: Hepatic expression of SSTR2 and COX-2 were upregulated in liver cirrhosis group compared with control group, both of which were inhibited by the addition of celecoxib. Celecoxib (20uM and 40uM) inhibited the upregulation of SSTR2 in L02 cell line transfected with COX-2 gene or treated with TAA, in which COX-2 was induced, compared with control group. DNA methylation level in promoter region of hepatic SSTR2 is similar between liver cirrhosis group and control group (3.7% VS 3.9%, p>0.05).

Conclusion: Hepatic expression of SSTR2 is upregulated in liver cirrhosis which may be regulated by COX-2 but not DNA methylation.

Disclosure of Interest: None declared

P0013 CHANGES IN GUT MICROBIOTA COMPOSITION ACCORDING TO NUTRITIONAL STATUS IN PATIENTS WITH LIVER CIRRHOSIS

F. R. Ponziani¹, S. Pecere¹, A. Tortora¹, V. Petito¹, B. E. Annicchiarico¹, M. Siciliano¹, F. Paroni Sterbini², A. Palladini², C. Graziani¹, L. Masucci², M. Pompili¹, M. Sanguinetti², A. Gasbarrini¹, on behalf of the GuLiver group

¹Internal Medicine and Gastroenterology, ²Institute of Microbiology, A Gemelli Hospital, Rome, Italy

Contact E-mail Address: francesca.ponziani@yahoo.it

Introduction: Gut microbiota (GM) contributes to host metabolism and energy balance, and significant modifications have been reported in malnourished populations. Liver cirrhosis is often associated with malnutrition and sarcopenia but GM changes in this setting have not been investigated yet.

Aims & Methods: The aim of this study was to assess whether GM composition may change in relation to nutritional status in cirrhotic patients. Fecal samples of cirrhotic patients without exposure to antibiotics, pre-/pro-biotics and bowel colonoscopy preparation for at least one month were collected. Nutritional status was assessed by two questionnaires including clinical and anthropometric parameters (Subjective Global Assessment, SGA, and Mini Nutritional Assessment, MNA). GM composition was assessed by a metagenomic gene-targeted approach (16S rRNA) using the Roche 454 GS Junior, following DNA isolation from stool samples stored at –80°C. Data were analyzed in Qiime. Biostatistic analysis was performed using R-statistics packages.

Results: Eighteen cirrhotic patients provided fecal samples. Median age was 60 years, Child-Pugh A/B/C 9/3/6, 3(66%) were well-nourished, 12(17%) at risk of malnutrition and 3(17%) severely malnourished according to MNA; 13(72%) were well-nourished, 2(11%) presented mild to moderate malnutrition and 3(17%) severe malnutrition according to SGA. PCoA of weighted-Unifrac distance evidenced samples clustering according to MNA and SGA rather than to Child-Pugh score (p=0.004, p=0.002 and p=0.284 respectively; PERMANOVA). Malnutrition was associated to the reduction of several taxa, mainly related to the genus Bacteroides, Parabacteroides, Prevotella, Streptococcus, Faecalibacterium, Veillonella (adj. p-value <0.05). These changes were not related to Child-Pugh score.

Conclusion: Changes in GM composition are strictly associated with nutritional status in cirrhotic patients. Metabolomic analyses should be performed to reveal the significance of these alterations and to evaluate potential therapeutic approaches.

Disclosure of Interest: None declared

P0014 THE ROLE OF HEPATITIS C VIRUS CORE ANTIGEN IN DIAGNOSIS OF HEPATITIS C VIRUS INFECTION

N. H. Ahmed¹, N. El-Gammal¹, E. A. G. Azazi², E. El-Shamy¹, S. A. Elhawari¹

¹Tropical Department, ²Microbiology Department, Zagazig University, Zagazig, Egypt

Contact E-mail Address: nabila.hassan25@yahoo.com

Introduction: Hepatitis C virus (HCV) infection is a major public health problem worldwide. The prevalence of infection is nearly 3% worldwide. Egypt has one of the highest prevalence rates of HCV infection in the world, about 16-18%. Blood donations screening, achieved mainly by serological identification of HCV-Antibody (Ab), has largely reduced HCV transmission. However, Ab detection is not a reliable marker in the pre-seroconversion phase of infection, infection stage assessing or/for monitoring individuals on anti-viral therapy. HCV Core Antigen (CAg) tests have been introduced to supplement anti-HCV tests and HCV PCR analyses. It may be a useful test for identifying window phase blood donations from Ab negative donors infected with HCV and for the monitoring of antiviral therapy.

Aims & Methods: In this study we aimed to analyze the clinical performance of a commercially available enzyme linked immunosorbent assay (Cell Biolab, Diagnostic. Inc. USA) for HCV CAg and compare the performance of it with reverse transcription polymerase chain reaction (RT-PCR).

This study was done on 88 persons who were divided into two groups. Group 1 included 44 persons diagnosed as anti HCV antibody positive and group 2 included 44 persons diagnosed as anti HCV antibody negative. Sera from all patients were analyazed for both HCV (CAg) and PCR tests. The positive cases to HCV infection in both groups and could be treated by anti HCV therapy reanalyzed by both HCV (CAg) and PCR tests after 12 week.

Results: Out of 88 patients; 26 patients were positive by both CAg and PCR; 5 patients were positive by CAg and negative by PCR while 2 patients were positive only by PCR test. The diagnostic sensitivity, specificity, and positive and negative predictive values of the HCV (CAg) test compared to the HCV RNA test were 92.9%, 91.7%, 83.9%, and 96.5%, respectively. There was statistically positive correlation (n=26, r=0.4) between of the patients HCV (CAg) titer and HCV RNA levels by RT-PCR in (P< 0.01). 12 cases (from 26 patients positive to HCV infection from both groups) that could be treated by antiviral therapy using interferon (IFN) and ribavirin (RBV) were reanalyzed by (CAg) and PCR tests after 12 week of therapy and there was a positive correlation (r=0.7) between of the patients HCV (CAg) titer and HCV RNA levels by RT-PCR in (P< 0.02).

Conclusion: HCV core antigen testing can be a reliable test used to identify current HCV infection and follow up of treatment especially in areas with poor facilities.

Disclosure of Interest: None declared

P0015 PATHOGENETIC ROLE OF SMALL INTESTINAL BACTERIAL OVERGROWTH IN NONALCOHOLIC STEATOHEPATITIS

S. Tkach¹, T. Cheverda¹

¹Internal Medicine #1, National Medical University, Kyiv, Ukraine

Contact E-mail Address: tkachsergio@yahoo.com

Introduction: Among the various potential contributions of the microbiota to liver disease, small intestinal bacterial overgrowth (SIBO) has historically been shown to be common in chronic liver disease, to correlate with its severity, to be linked to minimal and overt encephalopathy and increased risk of spontaneous bacterial peritonitis. Most recently, more credence has been given to a suggestion that the gut microbiota might play a role in the pathogenesis or progression of certain liver diseases, including alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) through the direct effects of bacteria or their products, via nflammatory mediators such as tumor necrosis factor-α.

Aims & Methods: Our aim was to evaluate the frequency of SIBO in patients with NAFLD/NASH and the influence of eradication of SIBO on clinical course of NASH. We investigated 104 obese patients (66 male, mean age – 54 years, mean BMI – 30.5 ±3 ,9) who were categorized into two groups: 54 patients with liver steatosis and 50 patients with NASH. Diagnosis of NALFD was confirm by use of ultrasonography or/and computed tomography. Diagnosis of NASH was based on increasing level of ALT (1.26 ± 0.18 mmol/l) and/or positive results of NASHTest (Poynard et al., 2006). In patients with NASH the evaluation of liver function with ¹³C-methacetine breath test (¹³C-MBT) also was performed (IRIS by WAGNER, Germany). The presence of SIBO was diagnosed by using a hydrogen glucose breath test (EC60 Gastrolyzer 2, Bedfont Scientific Ltd, Rochester, UK). All patients with positive results of hydrogen glucose breath test (H₂-GBT) were treated with rifaximine (1200 mg/day during 10 days). The efficacy of treatment was controlled with repeated biochemistry, H₂-GBT and ¹³C-MBT (after 1 month).

Results: Overall, positive results of H₂-GBT and presence of SIBO were found in 12 pts (22.2%) with liver steatosis and 28 (56%) with NASH (P < 0.005). Abnormal results of ¹³C-MBT were occurred in 2 pts with liver steatosis and SIBO (16.6%) versus 12 pts with NASH and SIBO (42.9%, P < 0.005). Eradication of SIBO was achieved in 34 of 40 pts (85%) after use of rifaximine (1200 mg/day during 10 days). Obvious improvement of the level of ALT (0.48 ±0.06, P < 0.005) and liver function with repeated biochemistry and ¹³C-MBT (after 1 month) was occurred in 22 pts (64.7%) and 18 pts (52.9%), accordingly.

Conclusion: We concluded that the changes of intestinal microbiota, including SIBO, plays an important pathogenetic role in initiation and progression of NASH. The modulation of intestinal microbiota and eradication of SIBO with antibiotics (rifaximine) decreased the level of liver inflammation, improved biochemical and liver functional indicators and can be considered as an effective and prospective method of treatment of NASH.

Disclosure of Interest: None declared

P0016 TRANSPLANTED HEPATIC STELLATE CELLS STIMULATE RAT LIVER REGENERATION AFTER PARTIAL HEPATECTOMY AND 2–ACETYLAMINOFLUORENE INJECTION

A. Titova¹, M. Mavlikeev², G. Pevnev²³, E. Sharipova²⁴, G. Burganova², M. Titova², A. Gumerova², A. P. Kiasov²

¹ Institute of Fundamental Medicine and Biology, ²Institute of Fundamental Medicine and Biology, Kazan Federal University, ³Human Anatomy Department, Kazan State Medical University, ⁴Human Anatomy Department, Kazan State Medical University, Kazan, Russian Federation

Contact E-mail Address: anjerika@list.ru

Introduction: In cases of insufficient efficacy of conventional therapy of chronic hepatitis and cirrhosis, the search for cellular sources of liver regeneration is becoming more and more urgent. One of the cell types claiming the role of liver regional stem cells (RSC) is hepatic stellate cell (HSC). The aim of our study was to investigate the influence of HSC transplantation on liver regeneration in rats after partial hepatectomy (PH) and administration of 2-acetylaminofluorene (AAF).

Aims & Methods: HSC were isolated from the intact rat livers by the collagenase-pronase perfusion method and then transfected with the green fluorescent protein gene (GFP). Isolated cells were injected immediately after performing PH into the portal vein of operated rats, which were administered with intraperitoneal injection of AAP for 5 days before PH and after PH till sacrifice date at a dose of 12 mg/kg per day. Animals were euthanized after HSC transplantation. Liver paraffin sections were stained immunohistochemically with antibodies against GFP, α-fetoprotein (a-FP) – marker of hepatoblasts, cytokeratin 19 (CK19) – marker of hepatoblasts and cholangiocytes.

Results: After the 1st day of HSC transplantation GFP-positive cells were not detected. After 2 days there were single GFP-positive hepatocytes. Their number reached maximum at 2–3 days after surgery and then rapidly decreased. At the early experimental stages CK19 was present only in the cells of intrahepatic bile ducts and in individual small cells in the periportal areas, the number of which had increased gradually till the 5th day, and up to this moment in the liver developed the evident ductular reaction: the number of bile ducts was increasing, their branching signs and holangioblasts’ migration were noted. Further, the evidence of the ductular reaction decreased, but there was also noted decrease of interportal distances indicating the formation of new liver lobules by dividing of existing ones. After the 1st day of PH and injection of native HSC, morphological analysis revealed multiple α-FP + hepatocytes. Besides, many hepatocytes had two cell nuclei. At the same time at all experimental dates we identified GFP + sinusoidal cells and small round α-FP + cells located in periportal sinusoids, which obviously were hepatoblasts. After the 2nd postoperative day the number of α-FP + hepatocytes sharply decreased, α-FP + binuclear hepatocytes and sinusoidal cells were still visible in parenchyma and periportal areas. After 2 weeks only single α-FP + sinusoidal cells were observed in the liver of HSC recipients.

Conclusion: We concluded that at the early stages of our experiment transplanted HSC stimulate activation of RSC in recipients’ liver presumably by releasing a variety of growth factors. This leads to expression of hepatoblasts markers cytokeratin-19 and α-FP by RSC localized in liver sinusoids. Later transplanted HSC begin to differentiate into the hepatocyte linage direction which is less pronounced. This probably occurs both due to the direct differentiation of transplanted cells and their fusion with host liver hepatocytes which is indirectly evidenced by the large number of GFP-positive binucleated hepatocytes.

Disclosure of Interest: None declared

P0017 ROLE OF HUMAN UMBILICAL CORD-DERIVED MESENCHYMAL STEM CELLS IN MANAGEMENT OF CARBON TETRACHLORIDE-INDUCED HEPATIC FIBROSIS IN SPRAGUE DAWELY RATS

D. Bakr¹, M. Maher¹, A. Lotfy¹, on behalf of medical experimental research center, S. El Desouky¹, on behalf of medical experimental research center, F. El Husseiny¹, on behalf of medical experimental research center, H. El Askalany¹, M. Hamed¹

¹Faculty of Medicine Mansoura University Egypt, Mansoura, Egypt

Contact E-mail Address: bakrdoaa@gmail.com

Introduction: Hepatic fibrosis is a reversible wound-healing response to either acute or chronic cellular injury that reflects a balance between liver repair and scar formation. During acute injury, the changes in liver architecture are transient and reversible. With chronic injury, there is progressive substitution of the liver parenchyma by scar tissue. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and often requires liver transplantation.

Chronic HCV is a major health problem in Egypt with a 10% prevalence of chronic HCV infection among persons aged 15-59 years, which, if left untreated, can result in cirrhosis and liver cancer.

Aims & Methods

Aim of work: To study the antifibrotic effect of umbilical cord mesenchymal stem cells (UCMSCs) and their ability for differentiation into functioning hepatocytes in early and late carbon tetrachloride(CCL4) induced hepatic fibrosis.

Methods: The study was conducted on 40 rats with average weight 180-200 gm, rats were housed under 25°C ± 2°C and a 12-h light/dark cycle in clean cages with access to food and water ad libitum.

Rats were divided into 2 main groups (control group and UCMSCs-treated group) and each one of them was subdivided into 2 subgroups:

Control group : consists of 20 rats and subdivided into 2 subgroups A) Negative control group (control vehicle (CV) group) : injected by olive oil intraperitonealy equivalent to their body weight and they were scarificed at 2and 6 weeks , blood samples and liver were taken for histopathological examination. B) Positive control group: Rats were injected by carbon tetrachrolide (CCl4) by dose 0.5 mg/kg in olive oil in ratio of 1:1 intraperitonially twice per week for 2 weeks (early fibrosis) and 6 weeks (late fibrosis).

UCMSCs-treated group: they were treated by UCMSCS after 2 weeks and 6 weeks of CCL4 injection in a dose of one million cells/cm3 medium by single injection into the inferior pole of the spleen under general anasthesia using mixture of valium (5mg/kg) and ketamine (5 mg/kg). Then, we closed the wound layer by layer using interrupted sutures by vicryl 3/0. Injection of subcutaneous saline into the rat to avoid its dehydration. Rats were sacrificed 2 weeks after treatment.

Results: As regard laboratory parameters, there was significant reduction in AST & ALT levels in UCMSCs-treated group when compared with the control group with minimal statistical difference in both albumin and INR with significant reduction in area of fibrosis ℅ and effective tracing of human albumin gene in the rat’s liver by RT-PCR technique in early and late fibrosis.

Conclusion: UCMSCs have both antifibrotic and regenerative powers in treatment of CCL4-induced liver fibrosis in rats at early and late stages.

Disclosure of Interest: None declared

P0018 GLUCAGON-LIKE PEPTIDE - 1 ANALOGUE LIRAGLUTIDE DOES NOT WORSEN CELL VIABILITY AND OXIDATIVE STRESS IN PRIMARY CULTURES OF RAT HEPATOCYTES ISOLATED FROM LEAN AND STEATOTIC LIVERS

J. Fontana¹, O. Kucera², M. Andel¹, Z. Cervinkova²

¹Centre for Research of Diabetes, Metabolism and Nutrition - Department of Biochemistry, Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague, Czech Republic, Prague 10, ²Department of Physiology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic

Contact E-mail Address: josef.fontana@lf3.cuni.cz

Introduction: Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in western countries, affecting 20-30% of adult population. This condition can progress to more severe liver diseases - nonalcoholic steatohepatitis, cirrhosis or hepatocellular carcinoma (1). Incretin hormone glucagon-like peptide-1 (GLP-1) exerts beneficial effects on liver functions and liver metabolism, especially in NAFLD condition. In our previous experiment we described a diminishing effect of GLP-1 analogue Liraglutide (LIRA) on an early phase of liver regeneration after partial hepatectomy in rats. In our present work we evaluated an effect of LIRA on cell viability and oxidative stress parameters in primary cultures of rat hepatocytes isolated from lean and steatotic livers.

Aims & Methods: Primary cultures of hepatocytes were obtained from male Wistar rats fed a standard laboratory diet (ST1-group, 10% of energy from fat) or a high-fat diet (HF-group, 71% of energy from fat) for 6 weeks. Hepatocytes were isolated by a two-step collagenase perfusion of rat liver, cell viability was >90%. After the establishment of monolayers, hepatocytes were incubated in supplemented Williams' E medium containing LIRA at concentrations of 0.1-1000 nmol/l for 24 hours. After this period the medium was collected for biochemical assays. We assessed cell viability (leakage of lactate dehydrogenase (LDH) and activity of cellular dehydrogenases - WST-1 assay), synthetic capacity of the hepatocytes (production of albumin determined by ELISA) and markers of oxidative stress (malondialdehyde concentration (MDA), and DCFDA assay).

Results: HF-groups vs. ST1-groups showed lower cell viability (lower cellular dehydrogenases activity, higher LDH leakage, p < 0.001) and increased MDA production (p < 0.001). LIRA increased activity of cellular dehydrogenases in ST1-groups (p < 0.01), decreased oxidative stress in steatotic hepatocytes (DCFDA assay, p < 0.05) and showed no negative effects on other parameters.

Conclusion: In conclusion, GLP-1 analogue Liraglutide does not exhibit negative effects on cell viability and oxidative stress in primary cultures of rat hepatocytes isolated from lean and steatotic livers.

This work was supported by grants GAUK 1488213 and PRVOUK P37/02.

Disclosure of Interest: None declared

P0019 THE ROLE OF ALBUMIN AND HEPATIC ELASTOGRAPHY LEVELS ON VITAMIN D DEFICIENCY

M. Silva¹, A. Peixoto¹, H. Cardoso¹, G. Macedo¹

¹Gastrenterology, Centro Hospitalar São João, Porto, Portugal

Contact E-mail Address: marcocostasilva87@gmail.com

Introduction: Liver is the major organ involved in vitamin D metabolism. Recent studies described a high prevalence of vitamin D deficiency in patients with different liver diseases and portal hypertension.

Aims & Methods

Aims: The authors propose to assess vitamin D deficiency in patients with liver disease and its association with clinical and analytical parameters related to hepatic and phospho-calcium metabolism.

Methods: Retrospective analysis of clinical records of patients followed on Hepatology Clinic in a single center. A vitamin D level <20ng/mL was considered as deficiency, according to guidelines. FibroScan transient elastography was used to estimate liver stiffness.

Results: In this study were included 250 patients: 156 men with a median age of 54 years, of which 38% patients had liver cirrhosis. The most common etiologies were VHB infection (31%), alcohol (18%) and VHC infection (16%). Median vitamin D levels were 16 (IQR: 15) ng/mL. Vitamin D deficiency was detected in 60% of total sample, 71% in those with cirrhosis and 53% in those without cirrhosis. Patients with vitamin D deficiency had lower calcium serum levels (p=0.004) and increased hepatic elastography (p=0.013). In multivariate analysis, using logistic regression, vitamin D deficiency was independently associated with liver cirrhosis (OR=2.2, p=0.005) and the albumin levels were a protective factor (OR=0.86, p=0.002).

Conclusion: Vitamin D deficiency is very common in liver disease, even without cirrhosis. This deficiency can lead to hypocalcemia, and should be prevented. Our results suggest that this deficiency may be primarily related with the severity of hepatic disease as reflected by the protective role of albumin levels and the association with cirrhosis and increased hepatic elastography.

Disclosure of Interest: None declared

P0020 THROMBOXANE A2 RECEPTOR SIGNALING PROMOTES LIVER REPAIR THROUGH PLATELET ADHESION TO THE SINUSOIDS DURING CHEMICAL-INDUCED HEPATOTOXICITY

T. Minamino¹, Y. Ito², T. Inoue¹, M. Majima³, S. Narumiya⁴, W. Koizumi¹

¹Department of Gastroenterology, ²Department of Surgery, ³Department of Pharmacology, Kitasato University School of Medicine, Sagamihara Sagamiono, ⁴Innovation Center for Immunoregulation Technologies and Drugs, Kyoto University Graduate School of Medicine, Kyoto, Japan

Contact E-mail Address: minamino@med.kitasato-.ac.jp

Introduction: Thromboxane A2 (TxA2) contributes to liver repair after acute liver injury as well as to tumor-associated angiogenesis.

Aims & Methods: The present study was to examine whether TxA2 receptor (TP) signaling in platelets facilitates sinusoidal restoration to repair the injured liver from chemical hepatotoxicity.

Treatment with carbon tetrachloride (CCl4) (1.0 mg/kg, ip) was used to induce acute liver injury in male TP knock out mice (TP-/-) and their wild counterparts (WT). At 0, 12, 24, 48, 72, and 96 h after CCl4 administration, plasma activity of ALT, necrotic area, proliferating cellular nuclear antigen (PCNA) index, and hepatic mRNA levels of growth factor relevant to angiogenesis were determined. Liver microcirculation was assessed by intravital microscopy.

Results: Both of WT and TP-/- experienced the maximal liver injury as evidenced by ALT levels at 24 h, and ALT levels were gradually decreased to basal levels at 96 h. Hepatic necrotic area in WT peaked at 48 h, and reduced thereafter, while that at 48 h in TP-/- was greater and remained high thereafter. The PCNA expression in WT peaked at 48 h, while that in TP-/- mice delayed and peaked at 72 h. Liver microcirculation was impaired and reached at nadir at 48 h, and delayed restoration in TP-/- compared with WT. Liver sinusoidal endothelial cell functional recovery was impaired in TP-/-. Platelets adhesion to the sinusoids was enhanced in WT at 48 and 72 h compared with TP-/-. This was associated with reduced mRNA levels of HGF, VEGFR2, basic FGF, and CD31 in liver from TP-/-. HGF levels in platelets from TP-/- treated with CCL4 for 48 h were lower than WT.

Conclusion: TP signaling promotes liver repair and sinusoidal restoration through enhancement of hepatic pro-angiogenic factors including HGF derived from platelets.

Disclosure of Interest: None declared

P0021 BACTERIAL INFECTION IN PATIENTS WITH LIVER CIRRHOSIS USING ACID SUPPRESSIVE MEDICATION: AN EXPERIENCE OF A SINGLE TERTIARY HOSPITAL IN QATAR

A.-N. Elzouki¹, N. Nefati¹, F. Rasoul¹, O. Othman¹, A. Saad¹, A. Badi¹

¹Medicine, Hamad Medical Corporation, Qatar, Doha, Qatar

Contact E-mail Address: nelzouki_1999@yahoo.com

Introduction: The association between bacterial infections and acid suppressive medications (i.e., proton pump inhibitors, PPIs) has been recently studied with debatable results.

Aims & Methods: The aim of this study was to investigate the relationship between PPIs and the development of bacterial infections in cirrhotic patients.

Consecutive cirrhotic patients above 18 years old hospitalized from 2007 through 2012 to Hamad General Hospital-Qatar were enrolled. We specifically inquired for PPIs consumption in the last 90 days prior to hospitalization and classify as PPIs-users and non-users. Cirrhosis diagnosis was established either with a liver biopsy or the combination of physical, laboratory and ultrasonography findings. Cirrhotic patients with active gastrointestinal bleeding, using immunosuppressive therapy or using antibiotics in the previous two weeks prior to hospitalization were excluded.

Results: A total of 333 patients were included, 171 (51.4%) with and 162 (48.6%) without PPIs. The PPIs-users were significantly older in age (p=0.001). There was no statistical difference between the two groups in sex distribution and etiology of cirrhosis (p > 0.05 for both parameters). The PPIs-users had a significantly higher incidence of overall bacterial infection rate (25.7%) than non-PPIs-users (13.5%), p=0.005. On the multivariate analysis, older age >60 years, (p = 0.02), and PPIs-use (p= 0.01) were independent predicting factors for overall bacterial infection. The indication for PPIs use was undocumented in 43% of patients.

Conclusion: The present study shows that PPIs use, as well as older age >60 years, were independent predicting factors for the development of bacterial infection in hospitalized cirrhotic patients. Unless it is indicated, PPI therapy should be avoided in this group of patients, in particular those older than 60 years of age.

Disclosure of Interest: None declared

P0022 PREVALENCE OF MALNUTRITION IN ADVANCED CIRRHOSIS – A PROSPECTIVE NUTRITIONAL ASSESSMENT IN HOSPITALIZED PATIENTS

A. R. Alves¹, C. Reis², S. Giestas¹, D. R. Branquinho¹, D. Perdigoto¹, M. Gravito-Soares¹, E. Gravito-Soares¹, L. Santos³, M. H. Loureiro⁴, P. Figueiredo¹, C. Sofia¹

¹Gastroenterology Department, Coimbra Hospital and University Centre, ²Faculty of Medicine, University of Coimbra, ³Internal Medicine A Department, ⁴Dietetics and Nutrition Unit, Coimbra Hospital and University Centre, Coimbra, Portugal

Contact E-mail Address: alvess.anarita@gmail.com

Introduction: Malnutrition is a risk factor for increased morbidity and mortality in liver cirrhosis. Nutritional assessment has been recognized as an important step to identify cirrhotic patients at greater risk of complications in clinical practice.

Aims & Methods

Aim: To evaluate nutritional status of hospitalized patients with decompensated liver cirrhosis.

We performed a prospective six-month study in a gastroenterology unit. All consecutive patients hospitalized due to decompensated liver cirrhosis were submitted to nutritional assessment by the following methods: anthropometric parameters (body mass index-BMI, skinfolds and circumferences), biochemical parameters, dynamometry and questionnaires. Demographic and relevant clinical data were also collected.

Results: A total of 50 patients were included, with a mean age of 60.9 ± 12.1 years, predominantly male gender (80.0%) and alcoholic cirrhosis (90.0%). Main admission causes: ascites and edema 24.0%, hepatic encephalopathy 20.0%, digestive hemorrhage 18.0% and spontaneous bacterial peritonitis 10.0%. All patients except two were classified as Child-Pugh B or C (B-36.0%; C-58.9%) and presented high MELD scores (mean 19.2 ± 7.3). The prevalence of malnutrition, according to the different methods used, was: BMI 22.0%, triceps skin thickness 86.0%, midarm circumference 78.0%, midarm muscle circumference 78.0%, Mini Nutritional Assessment 32.0% (with 62.0% of patients at risk), Subjective Global Assessment 86.0% and the Royal Free Hospital Global Assessment 86.0%. Malnutrition in Child-Pugh C patients was significantly higher comparing with Child-Pugh B, with all the methods used (p < 0.05), except for BMI (p > 0.05). MELD score was significantly higher in malnourished patients, compared with non malnourished patients (27 versus 13), independently of the method (p < 0.05).

Conclusion: Prevalence of malnutrition in advanced cirrhosis was superior to 70% with all the evaluation methods, except for BMI. Greater severity of disease was associated with higher prevalence of malnutrition.

Disclosure of Interest: None declared

P0023 CIRRHOTIC CARDIOMYOPATHY DOES NOT INFLUENCE MORTALITY OR MORBIDITY IN A PROSPECTIVE COHORT OF CIRRHOTIC PATIENTS

A. Voiosu¹², I. Daha²³, T. Voiosu¹², B. Smarandache¹, A. Radoi², M. Rimbas¹², B. Mateescu¹², R. Voiosu², M. Diculescu²⁴, on behalf of ACCEPT

¹Gastroenterology, Colentina Clinical Hospital, ²Carol Davila University of Medicine , ³Cardiology, Colentina Clinical Hospital, ⁴Gastroenterology, Fundeni Clinical Institute, Bucharest, Romania

Contact E-mail Address: andreivoiosu@yahoo.com

Introduction: Cirrhotic cardiomyopathy (CCM) is a clinically silent complication of liver cirrhosis that becomes overt after stressful events such as infections, placement of transjugular intrahepatic portosystemic shunts or liver transplant. Diagnostic criteria as well as clinical relevance of this entity in patients suffering from cirrhosis are currently under debate.

Aims & Methods: We aimed to determine the impact on survival and disease-related adverse events in a cohort of consecutive patients with liver cirrhosis.

Seventy cirrhotic patients examined in our tertiary referral centre were enrolled in a prospective observational study. Prior history of cardiovascular disease, diabetes, acute renal failure, severe anaemia, obesity or cachexia, active malignancy, infections were considered exclusion criteria.

Full physical examination, routine blood work, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, 12-lead electrocardiograms and transthoracic echocardiography examination with tissue Doppler imaging were performed in all patients. CCM was diagnosed according to the consensus criteria [1] in the presence of left ventricular ejection fraction <55% and/or diastolic dysfunction (E/A < 1, E wave deceleration time >200ms, isovolumetric relaxation time >80ms).

Patients were contacted by telephone every 3 months and invited for a study visit one year after enrollment. Disease-related adverse events (gastrointestinal bleeding, encephalopathy, new-onset or worsening of ascites, severe infections, hepatocarcinoma) and death were the main outcomes reported. Patients were stratified according to the presence of CCM and hypothesis testing was two-tailed with p < 0.05 considered significant. Survival analysis was performed by Kaplan-Meier curves.

Results: According to consensus criteria cirrhotic cardiomyopathy was diagnosed in 31 patients (44%). 3 patients were lost to follow-up. There was no difference in etiology or severity of cirrhosis amongst the groups. NT-proBNP levels and length of rate adjusted QT interval did not differ significantly according to the presence or absence of CCM (189 vs 238 pg/mL and, respectively, 414 vs 420 ms). During follow-up (range:3-15 months) there were 10 deaths and 31 patients experienced at least one disease-related adverse event. The median time to appearence of decompensation was 9 months. There were no significant differences between patients with and without CCM in rate of death (4 vs 6 patients, p=0.9), risk of adverse-event (14 vs 17 patients, p=0.1). There was a statistically insignificant trend towards earlier decompensation in the CCM group (8.8 vs 10.2 months, p=0.2). Higher MELD score was the only risk factor for earlier decompensation.

Conclusion: Cirrhotic cardiomyopathy has a high prevalence in the general population of patients with cirrhosis when consensus criteria are used for diagnosis. The presence of cirrhotic cardiomyopathy did not influence survival or time to first decompensation during up to 15 months follow-up in this cohort.

Disclosure of Interest: None declared

P0024 MEAN PLATELET VOLUME AS A NONINVASIVE MARKER FOR PREDICTION OF INFLAMMATION AND INFECTION OF ASCITIC FLUID IN DECOMPENSATED CHRONIC LIVER DISEASE

A. G. Antunes¹, M. Eusébio¹, A. Vaz¹, P. Queirós², T. Gago¹, P. Caldeira¹, B. Peixe¹, H. Guerreiro¹

¹Gastroenterology Department, Centro Hospitalar Do Algarve, Faro, ²Gastroenterology Department, Centro Hospitalar Do Algarve, Portimão, Portugal

Contact E-mail Address: sergiogiao@hotmail.com

Introduction: One of the most important complication of cirrhosis is ascitic fluid infection (AFI) and occurs in up to 25% of patients. Current literature suggests that ascitic fluid analysis by paracentesis should be done for all patients with ascites that are admitted to the hospital to exclude AFI. Beside membrane inflammation, AFI is also associated with increased systemic inflammation. The mean platelet volume (MPV) as an indicator of larger, active platelets, is being widely studied as a marker for systemic inflammation in areas like Cardiology and Rheumatology, because of its low cost and availability in routine analysis (platelet count).

Aims & Methods: To evaluate the value of MPV as (1) an inflammation marker in decompensated chronic liver disease (2) its ability to exclude AFI.

Retrospective analysis of all patients admitted to our center with the diagnosis of decompensated chronic liver disease, between the period of 2010 and 2014. We excluded admissions for gastrointestinal bleeding and those where paracentesis was not done. At admission, patients were divided in 3 groups: with active infection, infected without AFI and with AFI. A receiver operating characteristics (ROC) curve was obtained, and sensitivity and negative predictive value were calculated for MPV as a predictive marker for AFI exclusion.

Results: We identified 434 patients, 232 with active infection and 99 with criteria for AFI.

The MPV was statistically higher in the group of patients with active infection compared to not infected (10.84 vs 10.43 fL; p = 0.000). Within the group of patients with active infection, those with criteria for AFI presented higher values of MPV (11.28 vs 10.49 fL; p = 0.000) compared to the other infections.

When compared, the MPV of patients with criteria for AFI versus the rest of the patients, the variables MPV (10.45 fL vs. 11.28; p = 0.000), leukocyte count (11.3 vs 8.7x10⁹ /L, p = 0.003) and CRP (65.30 vs 34.15 mg/L; p = 0.00) were significantly higher; no statistically significant differences were found for the variables number of platelets and platelet distribution width (PDW).

The ROC curve analysis suggested that the optimum MPV level cut-off point for cirrhotic patients with AFI, was 9.75 fL with a sensitivity of 92% and a negative predictive value of 91% (area under the curve: 0.701).

Conclusion: Our results show that MPV is significantly increased in patients with active infection, and represents a good marker for inflammation. We propose the MPV as a noninvasive useful marker for AFI exclusion, with an average discriminating power.

Disclosure of Interest: None declared

P0025 THE ROLE OF BIOMARKERS AND SYSTEMIC INFLAMMATORY RESPONSE SYNDROME IN THE EXCLUSION OF BACTERIAL INFECTION IN PATIENTS WITH DECOMPENSATED CHRONIC LIVER DISEASE

A. G. Antunes¹, M. Eusébio¹, A. Vaz¹, P. Queirós², T. Gago¹, P. Caldeira¹, B. Peixe¹, H. Guerreiro¹

¹Gastroenterology Department, Centro Hospitalar Do Algarve, Faro, ²Gastroenterology Department, Centro Hospitalar Do Algarve, Portimão, Portugal

Contact E-mail Address: sergiogiao@hotmail.com

Introduction: It is estimated that up to 35% of patients hospitalized for decompensated chronic liver disease have a bacterial infection ^(1-2). The usual biomarkers (C reactive protein- CRP, leukocyte count and mean platelet volume - MPV), together with criteria for systemic inflammatory response syndrome (SIRS), do not behave like in healthy population.

Aims & Methods: We sought to evaluate the diagnostic role of SIRS, CRP, leukocyte count and MPV as predictors of infection at admission in patients with decompensated chronic liver disease.

Retrospective study conducted from 2010 to 2014, which evaluated patients admitted to our center for decompensated chronic liver disease. We excluded gastrointestinal bleeding and those that had not had paracentesis. The patients were divided according to the presence or absence of active infection. We recorded demographic, clinical and laboratory data and assessed the effectiveness of SIRS, CRP, leukocyte count and MPV in predicting infection by using areas under the curve (AUCs).

Results: We identified 434 patients with a mean age of 60 years (80% male). Alcohol was identified as a causative agent for liver disease in 90% of patients and in 24% there was chronic viral infection. About 52% of patients were classified as Child-Pugh C and 13% had criteria for SIRS.

The variables CRP (57 versus 27 mg/L; p = 0.000), MVP (10.85 versus 10.42 fL; p = 0.000) and leukocyte count (10.54 versus 7.33x10⁹/L; p = 0.000) were significantly higher in the group of patients with active infection compared to uninfected. In univariate analysis, the presence of SIRS was associated with infection (X²: 55.6; p = 0.000, OR = 68). Regardless of the Child-Pugh score, when compared, the variables CRP (AUC: 0.754), leukocyte count (AUC: 0.633), SIRS (AUC: 0.621) and MPV (AUC: 0.600), CRP presented the highest discriminating power, and was statistically superior when compared to other variables (respectively, p = 0.0006; p <0.0001; p <0.0001). This superiority is still maintained whether is analyzed only Child-Pugh B patients or in Child-Pugh C patients.

Conclusion: The set of our results, only identified CRP as a good marker for exclusion of infection in patients with decompensated chronic liver disease. SIRS and the biomarkers MPV and leukocyte count showed an average discriminatory power (AUC <0.75).

Disclosure of Interest: None declared

P0026 PREVALENCE AND PREDICTORS OF MORTALITY IN PATIENTS WITH ACUTE-ON-CHRONIC LIVER FAILURE

H. Singh¹, C. G. Pai¹, S. Shetty¹, G. Balaraju¹

¹Kasturba Medical College, Manipal Univeristy, Manipal, India

Contact E-mail Address: cgpai@yahoo.co.in

Introduction: Acute-on-chronic liver failure (ACLF) is characterized by acute hepatic insult manifesting as jaundice and coagulopathy, complicated within 4 weeks by clinical ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease/cirrhosis, and is associated with high 28-day mortality.

Aims & Methods: To determine the prevalence of ACLF in patients with chronic liver disease and variables which predict mortality in the former condition. Consecutive patients with known or unknown chronic liver disease (CLD), admitted to Kasturba Hospital, Manipal, between May 2014 and February 2015 were included. ACLF was diagnosed at baseline in patients based on Asia Pacific Association for the Study of Liver (APASL) definition and all were given standard intensive care. All patients were followed up for 28 days or till mortality whichever was earlier. Univariate analysis and subsequently multivariate analysis was done to determine the factors which predict mortality in ACLF.

Results: 115 (male = 109) patients with CLD were included prospectively of whom 37 (32.2%) had ACLF. Alcohol was the most common cause of underlying chronic liver disease (80%) followed by cryptogenic (13.9%). Alcohol (62.16%), Hepatitis E infection (27.03%) and Reactivation of Hepatitis B virus (5.41%) were the most common acute insults. The 28-day mortality was 56.7% among those with ACLF and 23.1% in those without. On multivariate analysis, high serum creatinine (p=0.043) and high C-reactive protein (CRP) (p=0.044) were found to be independent predictors of mortality. Among the severity scores studied, Model for end-stage liver disease (MELD) score was individually able to differentiate between survivors and non-survivors (p=0.004) and fared better than Child-Turcotte-Pugh score (p=0.312).

Conclusion: Patients with ACLF have a higher mortality than those with CLD. High serum creatinine, high CRP and higher MELD scores predict poor outcome in patients with ACLF.

Disclosure of Interest: None declared

P0027 ROLE OF ACOUSTIC RADIATION FORCE IMPULSE ELASTOGRAPHY AND 13C-METHACETIN BREATH TEST IN PREDICTING THE SEVERITY OF CHRONIC LIVER DISEASE

C. Fierbinteanu-Braticevici¹, A. Moldoveanu¹, L. Tribus¹, A. Petrisor¹

¹Gastroenterology, University of Medicine Carol Davila, University Hospital Bucharest, Bucharest, Romania

Contact E-mail Address: cfierbinteanu@yahoo.com

Introduction: Noninvasive investigations, such as various imaging techniques and breath tests offer considerable promise in their ability to stage liver disease and avoid an invasive liver biopsy.

Aims & Methods

Aim: To evaluate the role of Acoustic Radiation Force Impulse (ARFI) elastography and ¹³C-methacetin breath test (MBT) in predicting the severity of chronic liver disease.

Methods: We performed ARFI elastography and ¹³C-methacetin breath test (MBT) in 179 patients with chronic liver disease of different etiologies (alcoholic, chronic hepatitis C, chronic hepatitis B and nonalcoholic fatty liver disease – NAFLD) who underwent liver biopsy for diagnosis and treatment. The METAVIR scoring system (chronic hepatitis C and chronic hepatitis B) and the Brunt scoring system (alcoholic hepatopathy and NAFLD) served as references for the histological staging of liver fibrosis. The accuracy of non-invasive tests to predict the severity of liver disease (Fibrosis ≥2 and cirrhosis) was assessed using the area under receiver operating characteristic curve (AUROC) with 95% CI.

Results: The Spearman’s correlation coefficient between ARFI (0.795) and MBT (0.678) and the histological diagnosis of NASH was highly significant (p < 0.001). The AUROC of ARFI elastography and MBT was 0.861 (95% CI = 0.808 - 0.914) and respectively 0.804 (95% CI = 0.740 - 0.867) for the diagnosis of significant fibrosis (F ≥ 2). The diagnostic accuracy of ARFI elastography in predicting cirrhosis (F=4) had a validity of 95.4% (95% CI AUROC = 0.928 - 0.981) while MBT had a validity of 82.7% (95% CI AUROC = 0.765 - 0.890, p < 0.001). MBT also enables the evaluation of the microsomal liver function involved in severe chronic liver disease.

Conclusion: ARFI Elastography and MBT are very good methods for assessing the severity of liver disease. Due to the complementary role in evaluating microsomal liver function, ¹³C-methacetin breath test could be a reliable diagnostic and follow-up test for patients with chronic liver disease.

Disclosure of Interest: None declared

P0028 THE IMPACT OF CARVEDILOL VERSUS NON-SPECIFIC BETABLOCKERS ON THE MORTALITY IN CIRRHOSIS

C. Sfarti¹, C. Cojocariu¹, A.-M. Singeap¹, C. Petrovici², O. Chiriac², A. Trifan¹, C. Stanciu²

¹Institute of Gastroenterology and Hepatology, University of Medicine and Pharmacy IASI, ²Institute of Gastroenterology and Hepatology, Institute of Gastroenterology and Hepatology, Iasi, Romania

Contact E-mail Address: cvsfarti@gmail.com

Introduction: Carvedilol is a good alternative to propranolol for the prophylaxis of variceal bleeding, some researchers suggesting even a greater impact on portal and systemic hypertension. There is still an open debate about the effect of carvedilol and non-specific betablockers (NSBB) on mortality in patients with cirrhosis.

Aims & Methods: We compared retrospectively the impact on mortality of carvedilol versus NSBB in patients with cirrhosis hospitalized in a tertiary referral center in Romania. We included patients with alcoholic and viral cirrhosis admitted in our center from 01 January 2010 to 31 December 2014. We defined risk time for the bleeding as the time between the first administration of betablockers until death or end of follow-up. We adjusted for age, gender, heart disease, variceal bleeding, Child-Pough score to assess the HR.

Results: We identified 2625 cases: 684 patients receiving carvedilol and 1941 patients who were treated with NSBB, respectively. There were 1147 (43.7%) cases with viral cirrhosis and 1478 (56.3%) cases with non-viral cirrhosis. Regarding the Child-Pough score in each group, we identified in the first group 431 (63%) Child A patients, 205 (30%) Child B patients and 48 (7%) Child C patients, while in the NSBB group we had 1296 (66.7%) Child A patients, 452 (23.3%) Child B patients and 193 (10%) Child C patients. The prevalence of variceal bleeding was 23.7% in the first group vs. 26.2% in the second group without significant difference, while the heart disease was significantly more frequent in the carvedilol group (57% vs. 24%). We recorded significantly fewer deaths in the carvedilol group during follow-up compared with the NSBB group (10.7% vs. 21.3%, Chi-square (p < 0.05). We found the un-adjusted HR for carvedilol vs. NSBB to be 0.56 (95% CI 0.3-0.7) and the HR adjusted for covariates was 0.58 (95% CI 0.3-0.7).

Conclusion: The use of carvedilol in patients with cirrhosis was associated with a significant lower mortality compared with the use of NSBB even though the variceal bleeding rate was similar between the two groups.

Disclosure of Interest: None declared

P0029 INCREASING FREQUENCY OF GRAM-POSITIVE COCCI IN SPONTANEOUS BACTERIAL PERITONITIS. A SINGLE CENTRE EXPERIENCE

C. Triantos¹, C. Grigoropoulou¹, N. Koukias¹, A. Zavitsanaki², M. Christofidou³, I. Spiliotopoulou³, C. Tsolias¹, V. Nikolopoulou¹, C. Karatza², K. Thomopoulos¹

¹Gastroenterology Department, ²General Medicine Department, ³Microbiology Laboratory, University Hospital of Patras, Patras, Greece

Contact E-mail Address: nkoukias@gmail.com

Introduction: Sponteneous bacterial peritonitis (SBP) in patients with hepatic cirrhosis is mostly related to gram negative enterobacteriaceae. Recent studies have reported a change in the epidemiology of microbes that are being isolated in SBP and an increased prevalence of gram positive and multiresistant bacteria.

Aims & Methods: Record the bacteria that have been isolated in the ascitic fluid of patients with hepatic cirrhosis and their resistance in commonly used antibiotics. Positive ascitic fluid cultures of cirrhotic patients that have been admitted in our hospital and the respective antibiograms have been retrospectively recorded.

Results: 62 patients (49 male) with hepatic cirrhosis with a median age of 66 years (32-68) had positive ascιtic fluid culture. In 36/62 cultures Gram + positive bacteria have been isolated. In detail the isolated bacteria were: enterococcus spp. (19), Escherichia coli (13), streptococcus spp (12), Klebsiella (6), staphylococcus (5), Proteasspp (2), Enterobacter (2) Acinetobacter (1), Cronobacter (1), Pseudomonas aurigonosa (1).

Resistance to 3^rd generation cephalosporines has been found in 20 out 47 strains, in ciprofloxacine in 20 out of 40 and in ampicilline in 29 out of 46.

Conclusion: Gram + bacteria have been isolatedin the majority of positive ascitic fluid cultures. Resistance to 3^rdgeneration cephalosporines and ciprofloxacine is common. Therapy should be individualized according to culture results and patients’ characteristics.

Disclosure of Interest: None declared

P0030 EARLY IN-PATIENT MANAGEMENT OF ALCOHOL-RELATED LIVER DISEASE: RESULTS OF A LIVER CARE BUNDLE TO IMPROVE QUALITY OF CARE

C. Mason¹, I. Huang-Doran¹, M. McPhail¹, S. Peake¹, K. Monahan¹, C. Collins¹

¹Department of Gastroenterology, West Middlesex University Hospital, London, United Kingdom

Introduction: The incidence of Alcohol Related Liver Disease (ARLD) is rising in the UK, as is its associated mortality. A recent National Confidential Enquiry into Patient Outcome and Death (NCEPOD) report highlighted recurring deficiencies in the management of ARLD in UK hospitals and the British Society of Gastroenterology provided guidance in the treatment of these patients during acute hospital admissions.

Aims & Methods: Between 1 August 2013 and 31 October 2013, consecutive admissions of patients with ARLD to a district general hospital were identified from discharge and mortality data. A liver care bundle (LCB) using NCEPOD recommendations was generated. Case notes were analysed prior to institution of this LCB and re-audited following its inception from 1 April 2014 to 31 July 2014. Electronic referrals to specialist gastroenterology and dieticians formed part of the LCB, as well as a checklist of actions for the admitting physician.

Results: 20 patients (median age 51 (28-67) years) were identified initially with ARLD, of which 13 (65%) were male. Median Model for End-stage Liver Disease (MELD) score was 14 (range 6-35). Post LCB institution a further cohort of 25 patients studied was matched for age (59 (32-79) years), sex (13/25 (52%) male) and MELD score (13 (6-40)). Inpatient mortality was 7/20 (35%) prior to and 2/23 (9%) post LCB (p=0.065). All patients were screened for ongoing alcohol use and in 65% a withdrawal regime was prescribed. Only 1/20 (5%) had dietician input in the first 48 hours rising to 11/25 (44%) post LCB institution (p < 0.001). In all patients with ascites in the presence of acute kidney injury, diuretics were discontinued in both cohorts. In 92% of cases of ascites, diagnostic parascentesis was performed, however blood cultures were performed on admission in only 6/20 (30%) initially rising to 40% post LCB. 13/20 of patients (65%) had consultant review within 12 hours pre LCB with 18/25 (72%) post LCB. The proportion of patients receiving specialist review by a gastroenterologist within 72 hours rose from 45% to 54% following LCB use.

Conclusion: Instituting a liver care bundle for the management of alcohol-related liver disease at our centre improved both the quality of care and outcome from patients admitted during acute decompensation, particularly related to early specialist review. Initiation of bundles of care in liver disease requires close collaboration between specialist medical services and allied health professionals such as dieticians to optimise patient care.

Disclosure of Interest: None declared

P0031 SPONTANEOUS BACTERIAL PERITONITIS IN PATIENTS WITH CIRRHOSIS AND ASCITES – ITS PREVALENCE, CLINICAL AND PARACLINICAL FEATURES

D. Matei¹², A. David¹, N. Al Hajjar¹², I. Groza², R. Prundus², V. Andreica¹², M. Tantau¹²

¹University of Medicine and Pharmacy Iuliu Hatieganu, ²Regional Institute of Gastroenterology and Hepatology , Cluj Napoca, Romania

Introduction: Spontaneous bacterial peritonitis (SBP) is a severe complication occurring in patients with liver cirrhosis and ascites and it is associated with a high mortality rate.

Aims & Methods: The aim of this study is to evaluate the prevalence of the SBP in hospitalised patients with cirrhosis and ascites and also their clinical and paraclinical characteristics.

Materials and methods. This cross-sectional study enrolled all patients diagnosed with liver cirrhosis and ascites , who were hospitalised in a tertiary medical center over a period of 18 months (January 2012- June 2013).

The diagnosis for SBP consists of polymorphonuclear (PMN) counts ≥ 250 cells/mm³ and/or a positive ascitic fluid culture, without any evidence of external or intra-abdominal infectious source.

To evaluate our patients, who were divided in two groups (SBP and non-SBP), we compared the following data: age, gender, etiology of cirrhosis, volume of ascitic fluid, hypotension, tachycardia, hepatic encephalopathy, upper gastrointestinal bleeding, hepatorenal syndrome, hepatocellular carcinoma, hepatic hydrothorax, leukocytosis and MELD Score (Model of End-stage Liver Disease).

Results: 763 patients with cirrhosis and ascites were included in our study. The mean age was 60.41 years (min 17 years, max 91 years) and there was a male predominance (63.3%). 11.1% of the patients had SBP.

By comparing the SBP and the non-SBP patients, the following significant differences were discovered: male gender 75.3% vs 61.8% (p=0.02); voluminous ascites 83.5% vs 31.6% (p < 0.001); hepatic encephalopathy 82.4% vs 54% (p < 0.001); hepatorenal syndrome 15.3% vs 2.5% (p < 0.001); hepatic hydrothorax 24.7% vs 11.7% (p=0.001); leukocytosis 32.9% vs 18% (p=0.002) and the MELD Score ≥ 17 points 68.2% vs 39.7% (p < 0.001).

Using multivariate analysis, four out of these factors were identified as being independent factors significantly associated with SBP: voluminous ascites (OR=8.33, 95%CI:4.50-15.42, p < 0.001), hepatic encephalopathy (OR=2.25, 95%CI:1.21-4.20, p=0.010), hepatorenal syndrome (HR=4.21, 95%CI:1.71-10.38, p=0.002) and the MELD Score ≥17 points (HR=1.77, 95%CI:1.03-3.02, p=0.037).

Conclusion: Spontaneous bacterial peritonitis was found in 11.1% patients with liver cirrhosis and ascites and was significantly associated with voluminous ascites, hepatic encephalopathy, hepatorenal syndrome and a MELD Score ≥ 17 points.

Disclosure of Interest: None declared

P0032 PANTOPRAZOLE VERSUS RABEPRAZOLE EFFECTS ON CYTOCHROME P450 ACTIVITY ASSESSED BY 13C-AMINOPYRINE BREATH TEST IN PATIENTS WITH LIVER CIRRHOSIS

A. Rocco¹, D. Angrisani¹, C. Rubicondo¹, M. Sanduzzi Zamparelli¹, D. Compare¹, P. Coccoli¹, L. Staiano², D. Amoruso², C. Coppola², G. Nardone¹

¹Department of Clinical Medicine and Surgery, Gastroenterology Unit, Federico II University, Naples, ²Hepatology and Interventional Ultrasound Unit, Gragnano Hospital, Gragnano, Italy

Contact E-mail Address: deborangrisani@hotmail.it

Introduction: Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide. Almost all PPIs, undergo extensive hepatic metabolism via cytochrome (CYP)-P450 system and their clearance significantly depend on CYP-2C19 activity. Otherwise, the primary pathway of rabeprazole metabolism is non-enzymatic. In patients with advanced liver disease, the activity of CYP-P450 system is impaired, thus leading to a drug clearance reduction and an increased risk of drug-drug interaction. 13C-aminopyrine breath test (13C-ABT) is a non-invasive, liver function test that explores CYP enzyme activity.

Aims & Methods: Aim of the study was to evaluate the effects of different PPIs on the activity of CYPs by 13C-ABT in patients with Hepatitis C virus (HCV)-related liver cirrhosis. We compared two PPIs with different metabolic pathway: pantoprazole, which employs the CYP-P450 pathway, and rabeprazole, which undergoes non-enzymatic metabolism.

Thirty consecutive patients with HCV-related liver cirrhosis, Child-Pugh A, needing PPI therapy, were randomly assigned to pantoprazole (40mg/day) or rabeprazole (20mg/day) treatment. Exclusion criteria were: other causes of liver cirrhosis, severe cardiovascular or respiratory disorders, use of PPI in the 30 days before the study. 13C-ABT was performed before and 15 days after starting therapy according to the following protocol: breath samples were collected baseline and at 30-minute intervals for 2 hours after oral administration of 13C-aminopyrine (2mg/Kg body weight). 13C-enrichment of CO2 was determined by purification-isotope ratio mass spectrometer. Results were expressed as maximum percentage of 13CO2-recovery per hour (max 13C% dose/h) at any time (“excretion peak”) and percentage of 13CO2-cumulative dose recovered in 2 h (%13C cum dose at 120 min).

Results: Overall, we enrolled 13 males and 17 females with a mean age of 60.9 ± 7.5 yrs. Age, gender distribution, BMI and laboratory findings did not significantly differ among pantoprazole and rabeprazole group. Baseline, 13C-ABT results were altered in 13/30 (43%) patients (6 in pantoprazole and 7 in rabeprazole group). Fifteen day after starting therapy, the pantoprazole group had a mean 13C-ABT %dose/h at 30 min of 6.20 ± 4 versus 6.35 ± 4.5 at baseline and a mean %dose/cumulative at 120 min of 11.52 ± 6.9 versus 11.27 ± 7 at baseline. Similarly, during rabeprazole treatment, the mean %dose/h at 30 min was 5.81 ± 3.9 versus 6.13 ± 4.3 at baseline and the mean %dose/cumulative at 120 min was 10.9 ± 6.5 versus 10.7 ± 7.5 at baseline.

Conclusion: No differences is detectable between pantoprazole and rabeprazole use in patients with HCV-related liver cirrhosis. Pantoprazole do not significantly impair the CYP-450 pathway activity in these patients. Both PPIs are safe for treatment of patients with advanced liver disease.

Disclosure of Interest: None declared

P0033 MANAGEMENT OF GASTRIC VARICES: A FRENCH NATIONAL SURVEY

D. Weil-Verhoeven¹, J.-P. Cervoni¹, N. Fares², M. Rudler³, C. Bureau², A. Plessier⁴, M.-T. Dao⁵, A. Pauwels⁶, D. Thabut³, P. Castellani⁷, F. Oberti⁸, N. Carbonell⁹, V. Di Martino¹, T. Thevenot¹, on behalf of Club Francophone pour l'Etude de l'Hypertension Portale

¹Hepatology, CHRU Jean Minjoz, Besançon, ²Hepato-Gastroenterology, CHU Purpan, Toulouse, ³Hepato-Gastroenterology, CHU Pitié-Salpêtrière, Paris, ⁴Hepato-Gastroenterology, CHU Beaujon, Clichy, ⁵Hepato-Gastroenterology, CHU de Caen, Caen, ⁶Hepato-Gastroenterology, CH de Gonesse, Gonesse, ⁷Hepato-Gastroenterology, Hôpital Saint-Joseph, Marseille, ⁸Hepato-Gastroenterology, CHU d'Angers, Angers, ⁹Hepato-Gastroenterology, CHU Saint Antoine, Paris, France

Contact E-mail Address: jpcervoni@chu-besancon.fr

Introduction: Gastric variceal bleeding accounts for 10% of upper gastrointestinal bleeding related to portal hypertension. Level of evidence in managing gastric varices is low.

Aims & Methods: We aimed to determine the modalities of management of non-GOV1 gastric varices in France. Hepato-gastroenterologists (HGE) working in general hospitals (GH) or in university hospitals (UH) received a self-administered questionnaire.

Results: One hundred and fifty four HGE from 109 centers (37UH, 72GH) among the 336 (32.4%) contacted responded. Regarding primary prophylaxis, beta-blockers were used by 96% of HGE. Only 17.2% of HGE used glue obliteration (UH: 27.7% vs GH: 9.3%; p=0.004), 8% used TIPS and 5.3% proposed no treatment. Most HGE (77.6%) estimated that they had local access to glue obliteration but 64.2% declared that TIPS placement required transfer to another center. Obliteration was performed under general anesthesia by 86% of HGE. N-butyl-2-cyanoacrylate plus methacryloxysulfolane (Glubran®) and N-butyl-2-cyano-acrylate (Histoacryl®) were used respectively in 48.2% and 55.9% of cases (3.5% of HGE used both). Dilution with lipiodol was performed in 78% of cases. The technique of obliteration was variable between centers and within the same center: maximal dilution was 1/10; injected volume varied from 0.5 to 20mL per varix and from 1 to 30mL per procedure. To control active bleeding, 77.6% of HGE used obliteration (UH: 85.7% vs GH: 70.9%, p=0.04) and 34% used band ligation (UH: 28.6% vs GH: 38.8%; p=0.02). Early-TIPS was proposed by 56.3% of HGE (UH: 71.7% vs GH: 39.2%, p < 0.001). Regarding secondary prophylaxis, 74.4% used betablockers, 66% used obliteration (UH: 76.6% vs GH: 56.6%; p=0.014) and 14% used TIPS. Endoscopic control was performed by 62.6% of HGE, 70% evaluated the varix stiffness with a closed biopsy forceps. Side effects of obliteration were reported by 59.5% of HGE (UH: 70.4% vs GH: 41.2%; p=0.08) and concerned mainly glue migration (UH: 66.7% vs GH: 33.3%; p < 0.001), an event systematically searched by 22.9%.

Conclusion: The management of gastric varices in France is very heterogeneous between centers and even within the same center. University hospitals have a better access to obliteration and especially to TIPS. Obliteration as a primary prophylaxis procedure was rarely performed. Glue migration was frequently observed although probably underreported. Specific guidelines on the management of gastric varices should be established by expert groups to standardize clinical practices.

Disclosure of Interest: None declared

P0034 EXTERNAL VALIDATION OF THE CLIF-SOFA IN CIRRHOTIC PATIENTS ADMITTED TO INTENSIVE CARE UNITS (ICUS): A META-ANALYSIS

D. Weil-Verhoeven¹, E. Levesque², M. McPhail³, R. Cavallazzi⁴, E. Theocharidou⁵, E. Cholongitas⁶, A. Galbois⁷, H. C. Pan⁸, C. J. Karvellas⁹, B. Sauneuf¹⁰, R. Robert¹¹, J. Fichet¹², G. Piton¹³, G. Capellier¹³, T. Thevenot¹, V. Di Martino¹, on behalf of METAREACIR Group

¹Hepatology, CHRU Jean Minjoz, Besançon, ²Centre Hépato-Biliaire, University Hospital Paul Brousse, Villejuif, France, ³Liver Intensive Care Unit and Institute of Liver Studies and Transplantation, King’s College Hospital, London, United Kingdom, ⁴Intensive Care Unit, University-Louisville, Louisville (KY), United States, ⁵Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital, London, United Kingdom, ⁶Liver Department, Aristotle University of Thessaloniki, Thessaloniki, Greece, ⁷Intensive Care Unit, University Hospital Saint Antoine, Paris, France, ⁸Nephrology Department, Chang Gung Memorial Hospital, Taipei, Taiwan, Province of China, ⁹Hepatology Department, Intensive Care Unit, University Of Alberta, Alberta, Canada, ¹⁰Intensive Care Unit, University Hospital of Caen, Caen, ¹¹Intensive Care Unit, University Hospital of Poitiers, Poitiers, ¹²Intensive Care Unit, University Hospital of Tours, Tours, ¹³Intensive Care Unit, CHRU Jean Minjoz, Besançon, France

Contact E-mail Address: vdimartino@chu-besancon.fr

Introduction: The prognostic performance of the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) score in cirrhotic patients admitted to Intensive Care Units deserves large external validations.

Aims & Methods: The aim of this meta-analysis was to assess the ability of the CLIF-SOFA to predict in-ICU, in-hospital, and 6-month mortality in ICU survivors.

The CLIF-SOFA was computed retrospectively in 6 studies including 1221 cirrhotic patients admitted between 1995 and 2012. Studies have been selected by the participation of the corresponding authors who responded to a standardized questionnaire. The prognostic performance of different cutoffs of the CLIF-SOFA to predict mortality at different timepoints was assessed by the weight-adjusted odds ratios and positive predictive values and compared to that of the SOFA, the modified SOFA (mSOFA) and the MELD.

Results: On admission, 72.1% of patients (n=880) had a CLIF SOFA ≤ 14 and only 1.1% (n=13) had a CLIF-SOFA > 22. Among all the available prognostic scores, the best predictor of in-ICU mortality was a CLIF-SOFA ≥ 22 (OR=5.94; CI95%: 1.71-20.64; p=0.005; PPV=1.00), followed by a SOFA > 19 (OR=10.37; 95%CI: 5.65-19.01; p < 0.001; PPV=0.94). Predictive value of in-ICU mortality was better for a CLIF-SOFA ≥ 15 (OR=7.44; CI95%: 3.43-16.12; p < 0.01; PPV=0.81) than for an increased SOFA on day 3 (OR=4.75; 95%CI: 2.33-8.97; p < 0.001; PPV=0.71) or a MELD score ≥26 (OR=5.37; 95%CI: 4.01-7.21; p < 0.001; PPV=0.66). Prognostic value of in-hospital mortality was good for a CLIF-SOFA ≥ 15 (OR=3.93; 95CI%: 2.13-7.26; p < 0.001; PPV=0.88), for a mSOFA > 13 (OR=11.92; 95%CI: 4.59-30.94; p < 0.001; PPV=0.94) and a SOFA > 19 (OR=11.56; 95%CI: 3.23-41.32; p < 0.001; PPV=0.94). Among ICU survivors, 6-month mortality was still predicted by a CLIF-SOFA ≥ 22 (OR=7.43; 95%CI: 1.18-46.62; p=0.032; PPV=1.00), and a MELD ≥26 (OR=3.97; 95%CI: 1.92-8.22; p < 0.001; PPV=0.75), whereas high values of SOFA and mSOFA did not provide any significant prediction.

Conclusion: In critically ill cirrhotic patients, the CLIF-SOFA is able to predict both in-ICU mortality and 6-month mortality in ICU survivors, conversely to the SOFA and mSOFA. High values of CLIF-SOFA better predict in-ICU mortality than high values of SOFA or increase in SOFA on day three, and better predict 6-month mortality in ICU survivors than the MELD score. The CLIF-SOFA thus appears as the prognostic score of choice for the critically ill cirrhotic patients.

Disclosure of Interest: None declared

P0035 SIX-MONTH MORTALITY OF CIRRHOTIC PATIENTS WHO SURVIVED INTENSIVE CARE: A META-ANALYSIS

D. Weil-Verhoeven¹, E. Levesque², M. McPhail³, R. Cavallazzi⁴, E. Theocharidou⁵, E. Cholongitas⁶, A. Galbois⁷, H. C. Pan⁸, C. J. Karvellas⁹, B. Sauneuf¹⁰, R. Robert¹¹, J. Fichet¹², G. Piton¹³, G. Capellier¹³, T. Thevenot¹, V. Di Martino¹, on behalf of METAREACIR Group

¹Hepatology, CHRU Jean Minjoz, Besançon, ²Centre Hépato-Biliaire, University Hospital Paul Brousse, Villejuif, France, ³Liver Intensive Care Unit and Institute of Liver Studies and Transplantation, King’s College Hospital, London, United Kingdom, ⁴Intensive Care Unit, University-Louisville, Louisville (KY), United States, ⁵Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital, London, United Kingdom, ⁶Liver Department, Aristotle University of Thessaloniki, Thessaloniki, Greece, ⁷Intensive Care Unit, University Hospital Saint Antoine, Paris, France, ⁸Nephrology Department, Chang Gung Memorial Hospital, Taipei, Taiwan, Province of China, ⁹Hepatology Department, Intensive Care Unit, University Of Alberta, Alberta, Canada, ¹⁰Intensive Care Unit, University Hospital of Caen, Caen, ¹¹Intensive Care Unit, University Hospital of Poitiers, Poitiers, ¹²Intensive Care Unit, University Hospital of Tours, Tours, ¹³Intensive Care Unit, CHRU Jean Minjoz, Besançon, France

Contact E-mail Address: vdimartino@chu-besancon.fr

Introduction: The medium-term survival of cirrhotic patients who survived intensive care and its determinants have never been evaluated, due to the small number of ICU survivors in the published studies.

Aims & Methods: This meta-analysis evaluated the predictors of 6-month mortality in ICU survivors.

13 studies (2695 cirrhotics) were analyzed after selection of original articles and response to a standardized questionnaire by the corresponding authors. The endpoint was 6-month mortality of 412 ICU survivors (reported in 5 studies). 95 pooled analyses concerned patient characteristics, reason for admission, organ replacement therapy, and composite scores.

Results: Only 48 patients (3.4%) were transplanted during follow-up. Six-month mortality was lower in high volume centers (OR=0.45; 95%CI: 0.30-0.67; p < 0.001), in general ICUs (OR=0.31; 95%CI: 0.21-0.47; p < 0.001) in centers with TIPS (OR=0.42; 95%CI: 0.25-0.46; p=0.002), but not with liver transplantation available (OR=2.21; 95%CI: 1.21-4.04; p=0.008). Age, sex and alcohol-related cirrhosis had no significant impact on 6-month mortality. Unlike for in-ICU mortality, high values of SOFA did not predict 6-month mortality in ICU survivors. Eight parameters of liver and renal function were associated with 6-month mortality, including Child-Pugh C stage (OR=2.43; 95%CI: 1.44-4.10; p < 0.001), MELD ≥ 26 on ICU admission (OR=3.97; 95%CI: 1.92-8.22; p < 0.0001; PPV=0.75), hepatorenal syndrome (OR=4.67; 95%CI: 1.24-17.64; p=0.022; PPV=0.88) and admission for acute renal failure (OR=3.29; 95%CI: 1.70-6.40; p < 0.001; PPV=0.73). Septic shock (OR=3.95; 95%CI: 1.38-11.30; p=0.010; PPV=0.62) and nosocomial infection on admission (OR=2.72; 95%CI: 1.09-6.76; p=0.031; PPV=0.76) were also associated with higher 6-month mortality. Among medical interventions, only the use of norepinephrine (OR=2.07; 95%CI: 1.07-4.00; p=0.029; PPV=0.61), given for hepatorenal syndrome, was predictive of 6-month mortality.

Conclusion: Only a minority of ICU survivors undergo liver transplantation. Liver and renal failures in ICU have a sustained impact on long-term mortality. The prognostic performance of general ICU scores decreases over time, unlike Child-Pugh and MELD scores, even measured in the context of organ failure. Eligible patients could thus be listed for transplantation in ICUs or shortly after ICU discharge.

Disclosure of Interest: None declared

P0036 IMPACT OF INFLAMMATION AND INFECTION ON SHORT- AND MEDIUM-TERM MORTALITY IN CIRRHOTIC PATIENTS ADMITTED IN INTENSIVE CARE UNITS: RESULTS FROM A META-ANALYSIS

D. Weil-Verhoeven¹, E. Levesque², M. McPhail³, R. Cavallazzi⁴, E. Theocharidou⁵, E. Cholongitas⁶, A. Galbois⁷, H. C. Pan⁸, C. J. Karvellas⁹, B. Sauneuf¹⁰, R. Robert¹¹, J. Fichet¹², G. Piton¹³, G. Capellier¹³, T. Thevenot¹, V. Di Martino¹, on behalf of METAREACIR Group

¹Hepatology, CHRU Jean Minjoz, Besançon, ²Centre Hépato-Biliaire, University Hospital Paul Brousse, Villejuif, France, ³Liver Intensive Care Unit and Institute of Liver Studies and Transplantation, King’s College Hospital, London, United Kingdom, ⁴Intensive Care Unit, University-Louisville, Louisville (KY), United States, ⁵Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital, London, United Kingdom, ⁶Liver Department, Aristotle University of Thessaloniki, Thessaloniki, Greece, ⁷Intensive Care Unit, University Hospital Saint Antoine, Paris, France, ⁸Nephrology Department, Chang Gung Memorial Hospital, Taipei, Taiwan, Province of China, ⁹Hepatology Department, Intensive Care Unit, University Of Alberta, Alberta, Canada, ¹⁰Intensive Care Unit, University Hospital of Caen, Caen, ¹¹Intensive Care Unit, University Hospital of Poitiers, Poitiers, ¹²Intensive Care Unit, University Hospital of Tours, Tours, ¹³Intensive Care Unit, CHRU Jean Minjoz, Besançon, France

Contact E-mail Address: vdimartino@chu-besancon.fr

Introduction: The impact of inflammation and infection on the outcome of cirrhotic patients admitted to Intensive Care Units (ICU) has been little studied.

Aims & Methods: This meta-analysis aimed to assess the ability of events related to inflammation or infection present on admission, to predict in-ICU mortality and to investigate whether inflammation or infection present on ICU admission was associated with 6-month mortality in ICU survivors. 13 studies (2695 cirrhotics) were analyzed after selection of original articles and response to a standardized questionnaire by the corresponding authors. The endpoint was the prognostic performance of 25 variables (including SIRS and its compounds, biochemical makers of inflammation, overt bacterial infection, germ involved, infection site) to predict short- and medium-term mortality.

Results: On admission, 57.5% of patients had ≥ 2 criteria for SIRS. Lung was the most common infected site (14.2%), followed by spontaneous bacterial peritonitis (11.4%). 12.8% of patients had positive blood culture(s). The most common bacteria were GN bacillus (GNB) (13.7%), followed by GP cocci (10.1%). Fungal infection was diagnosed in 3.9% of patients. Higher in-ICU mortality was predicted by 14 variables related to inflammation/infection, including fungal infection (OR=3.98; 95%CI: 1.28-12.36; p < 0.001; PPV=0.86), pneumonia-induced acute respiratory failure (OR=4.48; 95%CI: 4.60-18.15; p < 0.001; PPV=0.81), sepsis-related refractory oliguria (OR=9.14; 95%CI: 4.60-18.15; p < 0.001; PPV=0.79), sepsis-induced hypotension (OR=5.74; 95% CI: 3.41-9.71; p < 0.001; PPV=0.77), GNB infection (OR=2.24; 95%CI: 1.49-3.37; p < 0.00; PPV=0.70), community acquired infection (OR=2.37; 95%CI: 1.29-4.34; p < 0.001;PPV=0.68), the presence of ≥ 2 criteria for SIRS (OR=2.44; 95%CI: 1.64-3.65; p < 0.001; PPV=0.57), CRP > 29mg/dL (OR=1.82; 95%CI: 126-2.62; p < 0.001; PPV=0.57) and leucocytes < 4000/mm3 (OR=10.29; 95%CI: 6.63-16.00; p < 0.001; PPV=0.45). Most of these parameters better predicted in-ICU mortality than a MELD score ≥13 (OR=4.95; 95%CI: 2.47-9.89; p < 0.001; PPV=0.51), a Child Pugh stage C(OR=3.87; 95%CI: 2.47-6.07; p < 0.001; PPV=0.52), or a SOFA ≥ 7 (OR=7.70; 95%CI: 3.01-15.17; p < 0.001; PPV=0.53). Among ICU survivors, only nosocomial infection on admission (OR=2.72; 95%CI: 1.09-6.76; p=0.03; PPV=0.76) and admission for septic shock (OR=3.95; 95%CI: 1.38-11.29; p=0.01; PPV=0.62) were associated with higher 6-month mortality.

Conclusion: In critically ill cirrhotics, some parameters related to SIRS and infection are able to better predict short-term mortality than prognostic scores. A history of septic shock is a strong predictor of 6 month mortality, even after the control of organ failures allowing ICU discharge, and may become an indication for secondary antibioprophylaxis and/or liver transplantation. Nosocomial infection also have sustained impact on mortality.

Disclosure of Interest: None declared

P0037 ESOPHAGEAL VARICES BAND LIGATION IN THE PROPHYLAXIS OF VARICEAL HEMORRHAGE – EFFICACY AND SAFETY CONCERNS

D. Branquinho¹, R. Cardoso¹, S. Lopes¹, J. Pina Cabral¹, C. Sofia¹

¹Gastroenterology, Coimbra University Hospital (CHUC), Coimbra, Portugal

Contact E-mail Address: diogofbranquinho@yahoo.com

Introduction: Variceal hemorrhage is a severe complication of chronic liver disease with a well-known tendency to recur. Following the first episode, recurrence risk is over 60% in the following years. As such, safe and effective primary and secondary prophylactic strategies must be adopted.

Aims & Methods: All patients that underwent elective esophageal varices band ligation in 2012 and 2013 were followed for a year. Immediate, 24-hour and long term complications of these procedures were recorded. The success of this strategy was evaluated through its capacity to prevent new episodes of variceal bleeding.

Results: A total of 82 patients were submitted to 104 procedures with a 2-4 or 6-8 week interval until eradication of varices was achieved (male patients – 78%, average age – 63.8 ± 10.6 years-old; Primary prophylaxis – 73.2%, Secondary prophylaxis – 26.8%). Concomitant treatment with beta-blockers was prescribed to 43.9% of patients. Most patients were sedated by the Gastroenterologist (70.7%), while anesthetic support was adopted in 17% of the procedures. Immediate complications occurred in 10 patients (9.6%): self-limited bleeding in 6, while sclerotherapy was performed in 3 of them. In one patient, a Sengstaken-Blackmore balloon was placed to stop the hemorrhage. In the 24 hours after the procedure, no further complications occurred. In the following year, 14 patients had episodes of variceal hemorrhage (13.7%), on average about 7 months after the elective procedure. Six of them eventually died (5.8%). Variceal bleeding recurrence was less common in patients that underwent less frequent procedures (6-8 weeks).

Conclusion: Esophageal varices band ligation is an effective method to prevent both inaugural and recurrent episodes of bleeding. A larger time span between procedures is probably a safer option to prevent bleeding from scars. Its safety profile is good and the 24-hour admission for surveillance is not necessary as no further complications usually occur in that period.

Disclosure of Interest: None declared

P0038 CIRRHOTIC PATIENTS IN ICU WITH GASTRO-INTESTINAL BLEEDING MANAGED ACCORDING TO RECENT GUIDELINES DISPLAY ALTERED BRAIN HEMOGLOBIN OXYGEN’S SATURATION ASSESSED BY NEAR INFRARED SPECTROSCOPY

D. Thabut¹, M. Mallet¹, S. Tripon¹, M. Rudler¹, N. Weiss², on behalf of Brain Liver Pitie-Salpetriere Study Group (BLIPS)

¹Hepatological ICU, ²Neuro-ICU, La Pitie-Salpetriere Hospital, Assistance Publique - Hopitaux de Paris, PARIS, France

Contact E-mail Address: dthabut@gmail.com

Introduction: Near Infrared Spectroscopy (NIRS) is a non-invasive optical technique allowing a continuous measurement of brain’s hemoglobin saturation in oxygen (rSO2). It is considered as a surrogate marker of cerebral insult, and recognized as a useful tool in in cardiovascular surgery and neuromonitoring. A rSO2 < 50% is associated with increased neurological impairment and post-operative mortality. In cirrhotic patients with gastrointestinal bleeding (GIB), hemoglobin (Hb) threshold for transfusion has been recently lowered to 7g/dL. Some patients develop hepatic encephalopathy (HE) after GIB. In subarachnoid hemorrhage, a threshold of 7g/dL of Hb could worsen neurological outcome.

Aims & Methods: The aim of this study was to assess brain oxygenation using NIRS in cirrhotic patients with acute GIB admitted to ICU and managed according to recent guidelines, and to determine if brain injury was associated with Hb levels.

Cirrhotic patients admitted in ICU for acute GIB were prospectively included. Bilateral continuous recording of rSO2 was started upon admission using a NIRS monitor (INVOS 5100c Cerebral Oxymeter (Covidien©) with two sensors placed on the patient’s forehead. Minimal rSO2 (mini rSO2), average rSO2 (avr rSO2) and AUC of rSO2 50% (AUC50% rSO2), an integrated parameter depending on the depth/duration of desaturation under 50%, were extracted.

Results: 26 patients were included (median age: 60 years; 69%men). Etiology of cirrhosis was alcoholic 54%/ viral 19%/ NASH 23%/other 4%; Child Pugh A 15%/ B 20%/ C 65% and median MELD score 18. Median initial Hb was 7.9g/dL and nadir within 24 first hours was 7.8g/dL. 14 patients (54%) had a nadir of Hb below 8 g/dL within the 24 first hours, and 15 (58%) patients were transfused. Median mini rSO2 was 37% right/37% left, avr rSO2 46% right/48% left and AUC50% rSO2 1138 right/698 left. 22 patients (85%) had mini rSO2 < 50%. Mini rSO2 was significantly lower in patients having a nadir of Hb below 8g/dL. Mini rSO2, avr rSO2 and AUC50% rSO2 were independently correlated to initial Hb (p < 0.01 for all), nadir of Hb within the 24 first hours (p < 0.005 for all), and MELD score (p < 0.05 for all).

Conclusion: 85% of cirrhotic patients admitted to ICU for acute GIB and managed according to recent guidelines displayed mini rSO2 below 50% within 24 hours after admission. Low Hb levels within the 24 first hours were associated with brain desaturation. Further studies are mandatory to assess the influence of Hb thresholds on the development of HE.

Disclosure of Interest: None declared

P0039 CHANGES OF SERUM LEVELS OF CYTOKERATIN-18 FRAGMENTS IN PATIENTS WITH CHRONIC HEPATITIS C UNDER ANTIVIRAL THERAPY

A. Kandemir¹, I. Polat², M. Arabul³, E. Alper⁴, F. Aslan³, B. Unal³

¹Gastroenterology, ²Internal Medicine, Afyonkarahisar State Hospital, Afyonkarahisar, ³Gastroenterology, Izmir Katip Celebi University, Izmir, ⁴Gastroenterology, Izmir Katip Celebi University, Afyonkarahisar, Turkey

Contact E-mail Address: altaykandemri@yahoo.com

Introduction: Studies performed in the recent years have indicated that the cleavage level of serum CK-18 is correlated with hepatic fibrosis and disease severity in chronic hepatitis C and non-alcoholic steatohepatitis. Significant correlation between apoptosis level and responses to chronic viral hepatitis B and C treatments have shown a correlation between decreased CK18 levels during the treatment, and sustained viral response is also defined.

Aims & Methods: Our aim was to reveal the correlation between CK 18 level and treatment response in patients with chronic viral hepatitis C. 60 patients with diagnosis of chronic viral hepatitis C were enrolled to the study. Eligible patients for treatment criteria received PEG-interferon-ribavirin administration for 48 weeks. In Weeks 12-24, HCV RNA amount was measured at the end of treatment. Additionally, CK 18 levels were measured in Weeks 0-24 and at Week 72.

Results: Mean age of 60 patients was 52 ± 10.9 years. Of patients, 31 (51.6%) were in sustained viral response (SVR) group with the CK 18 level with CK 18 level of 116 ± 12.4 at the Week 24 of, whereas 29 (48.4%) were in non-SVR group with CK 18 level of 134 ± 23.5 (U/L). When the change in CK 18 levels between Week 0 (baseline value) and Weeks 24 and 72 in SVR-obtained patients and the level in the Week 24 in patients without SVR were compared, CK 18 levels in SVR-obtained patients were 243 ± 214 (U/L) in the Week 0, and 115 ± 12 (U/L) in the Week 24, thus the change was defined as 127 ± 209 (U/L), and the change was statistically significant (P= 0.014). While CK 18 level in the Week 0 was 270 ± 143 (U/L) in patients without SVR, it was 133 ± 19 (U/L) in the Week 24; the change was defined as 136 ± 156 (U/L). This change was statistically insignificant (P>0.5).

Conclusion: There are many studies proving clinically that disease progression and fibrosis, which are related to significant decreases in cytokeratin 18 levels in the circulation in hepatocellular apoptosis, are decreased in patients who had successful HCV clearance. Similarly, significant decrease was detected in CK 18 levels in SVR-obtained patients our study. However, no significant correlation was defined in recurrent and nonresponsive patients. In conclusion, it has been shown that hepatocellular apoptosis is significantly decreased in chronic viral hepatitis C patients by successful antiviral therapy; and CK 18 is a reliable marker to indicate apoptosis of hepatocyte. When the obtained data are evaluated, CK-18 can be used in the follow up of treatment efficacy and improvement in apoptosis level as well as it can be used as a non-invasive marker instead of liver biopsy.

Disclosure of Interest: None declared

P0040 NEWS TOOLS OF SCREENING VIRAL HEPATITIS IN REAL LIFE: NEW FRENCH MODEL OF CARE

A. J. Remy¹, H. Bouchkira¹, H. Wenger¹, S. Montabone¹

¹Mobile Hepatitis Team Hepatology Unit, Perpignan Hospital, Perpignan, France

Contact E-mail Address: andrejean.remy@orange.fr

Introduction: Hepatitis B and C screening was usually done by serology in laboratories or medical centers. If serology was positive, viral load and genotype was determined and after that patient saw hepatologist if viral load was also positive. Liver fibrosis was usually measured after first medical consultation. All steps took 3 to 6 months. Drug injection was main contamination route of hepatitis C virus (HCV) in France and western Europe since 1990. Although highest European screening rate in France, 44% of patients didn’t take care of hepatitis C. French guidelines were to treat all inmates and drug users, even fibrosis level.

Aims & Methods: Hepatitis Mobile team was created in July 2013. We proposed 10 services to patients and to our partners: 1/ Point of Care Testing POCT (HIV HBV HCV) 2/ Mobile liver stiffness Fibroscan* (indirect measurement of liver fibrosis) in site 3/Social screening and diagnosis 4/ Advanced on-site specialist consultation 5/ Easy access to pre-treatment commissions (“RCP”) with hepatologists, nurse, pharmacist, social worker, GP, psychiatric and/or addictologist 6/ Individual psycho-educative intervention sessions 7/ Collective educative workshops 8/ Staff training 9/ Drug users information and prevention 10/ Green thread: outside POCT and FIBROSCAN* with specific converted truck. So our French mobile mobile team proposed a new model of triple screening high risk patients for hepatitis C or B. All team members (nurses and social worker) came together in outreach centers, jailhouses, drug services centers and all structures which care for drugs users, homeless or other vulnerable patients. They offer triple screening at the same time: social screening with specific score of 11 questions called EPICES, POCT for HCV HBV (and also HIV if necessary) and liver fibrosis screening by FIBROSCAN*. With the results of triple screening, patient could do his/her biology quickly and see a hepatologist in 2 or 3 weeks only.

Results: 711 POCT were done in first 12 months; 19 were positive for new patients and 69 were positive for already known patients who returned to medical care by this pathway. One POCT was positive for HIV and 7 for HBV (but only done for 6 months); 393 FIBROSCAN* were done with medium rate of 7.8 KPa (fibrosis level F2): 68% for HCV, 3% for HBV and 29% for alcoholic liver disease. Social screening showed that 91% of our patients were vulnerable. 134 patients were addressed by on site hepatologist consultations and 112 came almost at one time. 45% of patients were treated and only 3% were lost to sight. All these patients had access to new direct antiviral agents. Follow up of treated patients showed only one relapser for 41 finished treatments.

Conclusion: In our model of care, triple screening by mobile services and follow up was necessary and successful to increase number of patients diagnosed, treated and cured.

Disclosure of Interest: A. J. Remy Financial support for research: GILEAD, Consultancy: GILEAD BMS ABBVIE JANSSEN, H. Bouchkira: None declared, H. Wenger: None declared, S. Montabone: None declared

P0041 MEASURING QUALITY OF LIFE IN HCV-INFECTED PATIENTS TODAY: THE BURDEN OF A “LIMITED” ACCESS TO THE NEW ANTI-VIRAL DRUGS

A. Rocco¹, D. Angrisani¹, M. Carbone¹, D. Compare¹, G. Nardone¹

¹Department of Clinical Medicine and Surgery, Gastroenterology, Federico II University, Naples, Italy

Contact E-mail Address: deborangrisani@hotmail.it

Introduction: The Health Related Quality of Life (HRQoL) in patients with chronic HCV infection is significantly impaired in respect to uninfected people and directly correlates with severity of hepatic dysfunction. The achievement of a sustained virological response (SVR) is associated with a significant and long-lasting improvement in the HRQoL. The recent introduction of new potent direct antiviral agents seems to promise the definitive cure for HCV infection in almost the totality of infected individuals. However, the economic burden of the therapeutic schedules significantly limits the access to therapy particularly for patients with early stage liver disease.

Aims & Methods: To evaluate the impact of the awareness of new therapy availability on HRQoL, anxiety, depression and stress in patients with early-stage of HCV-related liver disease.

A set of questionnaires was administered to consecutive patients with chronic active HCV-related diseases to evaluate the HRQoL (Short Form Health Survey, SF-36), the depression, anxiety and stress levels (Depression Anxiety Stress Scale, DASS-42) and the perception of discrimination for such a difficult therapy access (Visual Analog Scale, VAS).

Exclusion criteria were: clinical, laboratory or histological signs of liver cirrhosis, concomitant liver diseases (HBV infection, autoimmunity or alcohol abuse) or hepatocellular carcinoma, HIV coinfection, <3 years of education, diagnosis of major depression or other psychiatric disorders, current use of antidepressant medications or other pharmaceuticals known to affect cognitive function, cerebrovascular disease.

Results: Sixty patients with active chronic HCV infection (HCV-RNA +) and 36 patients with SVR to prior treatment were enrolled. There were… male, mean age was 60.6 years (range 32-74 years).

Patients with chronic active HCV infection showed significantly lower scores than the SVR group, in the following SF-36 domains: “Physical Functioning” (70 ± 26.2 vs 81.6 ± 22.2; p = 0.001), “General Health” (45.9 ± 22 vs 63.3 ± 17.7; p <0.0001), “Vitality” (55.8 ± 23.6 vs 65.8 ± 24.6; p = 0.001) and “Role-Physical” (69.8 ± 25.1 vs 87.4 ± 18.7; p < 0.0001).

In addition, patents with showed higher scores, compared to the SVR group, in all the three DASS-42’s scales: “Depression” (10.5 ± 8.4 vs 6.9 ± 6.5; p = 0.03), “Anxiety” (10.6 ± 7.2 vs 7.2 ± 6.1; p = 0.02) and “Stress” (13.4 ± 7.5 vs 9.3 ±7.5; p = 0.012).

Finally, the mean VAS score for the perception of discrimination was 7.27 ± 2.62.

Conclusion: The awareness of new effective antiviral drugs and, at the same time, the limited access to therapies significantly reduce the HRQoL and increase depression, anxiety and stress in patients with chronic active HCV infection.

Disclosure of Interest: None declared

P0042 HIGH RISK OF INFECTION DURING TRIPLE THERAPY WITH FIRST-GENERATION PROTEASE INHIBITORS: A NATIONWIDE RETROSPECTIVE COHORT STUDY

F. A. Berden¹, I. van Zwietering¹, R. Maan², R. J. de Knegt², W. Kievit³, J. P. Drenth¹

¹Gastroenterology and Hepatology, Radboud university medical center, Nijmegen, ²Gastroenterology and Hepatology, Erasmus MC university medical center, Rotterdam, ³Health Evidence, Radboud university medical center, Nijmegen, Netherlands

Contact E-mail Address: Floor.Berden@Radboudumc.nl

Introduction: Peginterferon (PegIFN) remains the backbone of therapy for chronic hepatitis C (CHC) in many economically constrained regions, as all oral regimens are not globally available. However, PegIFN has a high rate of (serious) adverse events, frequently reported is neutropenia due to bone marrow suppression. Addition of a first-generation protease inhibitor (telaprevir or boceprevir) to PegIFN and ribavirin (RBV) can lead to a higher risk of neutropenia. Guidelines recommend dose reduction or treatment discontinuation in case of moderate or severe neutropenia out of concern for infections.

Aims & Methods: The aim of this study is to assess the risk of infections during first-generation protease inhibitor-based therapy in clinical practice and its relation to treatment-induced neutropenia. This nationwide multicenter retrospective cohort study included CHC patients treated with PegIFN, RBV and telaprevir or boceprevir in 37 centers in the Netherlands. Absolute neutrophil counts (ANC) were divided in 3 categories: severe (<500/µL), moderate (500-750/µL) and mild (750-1500/µL). Likewise, infections were classified as severe (i.v. treatment with antibiotics or hospitalization), moderate (oral or topical antibiotics or antimycotics) or mild (no treatment). We assessed associations between risk factors and infectious events adjusting for multiple measurements with multivariable logistic regression analysis.

Results: We included 409 CHC patients: 233 telaprevir and 176 boceprevir treated patients. In our cohort 277 (68%) patients were male, mean age was 50.4 (range 19-77) years and 236 (58%) patients were treatment naive. Based on liver biopsy, fibroscan, ultrasound or FIB-4 index, 127 (31%) patients were classified as cirrhosis.

A total of 238 infections occurred in 156 patients (38%) and 35 (15%) were severe occurring in 29 (7.1%) patients. Mean baseline ANC was 3.421/µL and 4.4% of patients had a baseline ANC <1500/µL. During treatment 274 patients developed neutropenia (severe, n=28). In 40 patients ANC was missing. Multivariable analysis showed that female sex (OR 1.81, 95 CI 1.30-2.51, p < 0.001), diabetes mellitus (OR 1.50, 95 CI 1.04-2.16, p=0.030), COPD (OR 2.77, 95 CI 1.72-4.46, p < 0.001) and history of decompensated liver cirrhosis (OR 1.69, 95 CI 1.04-2.75, p=0.033) were associated with the infection incidence. Neutropenia at the previous visit was not associated with infection (univariable analysis: OR 0.83, 95 CI 0.59-1.15, p=0.263).

Conclusion: This nationwide multicenter retrospective cohort study showed that triple therapy with first generation protease inhibitors was complicated by an infection in 38% of patients. The majority of infections were mild or moderate. Female gender, diabetes mellitus, COPD and a history of decompensated liver cirrhosis were associated with an increased risk of infections during treatment, suggesting that these patients should be monitored carefully.

Disclosure of Interest: F. Berden: None declared, I. van Zwietering: None declared, R. Maan Consultancy: AbbVie, R. de Knegt Financial support for research: BMS, Roche, Janssen, Lecture fee(s): AbbVie, BMS, Gilead, Roche, Norgine, Consultancy: AbbVie, BMS, Gilead, Norgine, W. Kievit: None declared, J. Drenth Financial support for research: AbbVie, Falk, Ipsen, Novartis, Zambon, Consultancy: AbbVie, Gilead, Janssen, BMS

P0043 COMPROMISED SAFETY OF FIRST-GENERATION PROTEASE INHIBITORS IN CHRONIC HEPATITIS C PATIENTS WHO DO NOT MEET INCLUSION CRITERIA FOR REGISTRATION TRIALS. NATIONWIDE REAL-WORLD EXPERIENCE

F. A. Berden¹, R. J. de Knegt², J. den Hollander³, M. G. van Vonderen⁴, P. Friederich⁵, B. van Hoek⁶, K. M. van Nieuwkerk⁷, J. P. Drenth¹, W. Kievit¹

¹Radboud University Medical Center, Nijmegen, ²Erasmus Medical Center, ³Maasstad Hospital, Rotterdam, ⁴Medical Center Leeuwarden, Leeuwarden, ⁵Catharina Hospital, Eindhoven, ⁶Leiden University Medical Center, Leiden, ⁷VU Medical Center, Amsterdam, Netherlands

Contact E-mail Address: Floor.Berden@Radboudumc.nl

Introduction: Registration of drugs in chronic hepatitis C (CHC) is supported by phase 3 trials. These randomized controlled trials preserve internal validity using strict eligibility criteria which may limit the generalizability of findings.

Aims & Methods: This study aims to compare effectiveness and safety of boceprevir and telaprevir based treatment in CHC clinical practice patients who would qualify (WQ) and would not qualify (WNQ) for phase 3 trials. We performed a nationwide multicenter retrospective cohort study of CHC genotype 1 patients treated with boceprevir or telaprevir in 37 centers in the Netherlands. We compared sustained virological response (SVR) and serious adverse events (SAE) in WQ vs. WNQ patients. Phase 3 clinical trials were identified through systematic review [1-5], eligibility criteria of original protocols were applied to clinical practice population to determine WQ and WNQ. Given comparable SVR in treatment naive (TN) and relapse patients, we combined these groups in the analysis.

Results: This study includes 409 CHC patients, 236 TN and 173 treatment experienced: 71 relapse and 102 prior nonresponders (NR), viral breakthrough or early discontinuation patients (NR-group). In total, 35% to 49% of TN and relapse patients would not qualify for one of the phase 3 trials (Table). WNQ patients treated with boceprevir have lower SVR rates (p=0.048) and a trend for higher SAE rates (p=0.06) than WQ patients. WNQ patients on telaprevir had similar SVR rates, but higher SAE rates than WQ patients (p=0.037 and p=0.011). Between 48% and 52% of NR-group patients would not qualify for trials, but there SVR and SAE rates were comparable between WQ and WNQ.

P0043 Table.

SVR and SAE in WQ vs. WNQ patients.

	Phase 3 trial	n	n WQ (%) / n WNQ (%)	SVR % WQ / WNQ	p	SAE % WQ / WNQ	p
Boceprevir	SPRINT2/RESPOND2a	134	68(51)/66(49)	76.5/60.6	0.048	7.4/18.2	0.06
	RESPOND 2b	42	20(48)/22(52)	45.0/40.9	0.789	10.0/27.3	0.155
Telaprevir	ILLUMINATE/ADVANCEa	173	107(62)/66(38)	72.9/65.2	0.28	16.8/30.3	0.037
	REALIZEa	173	112(65)/61(35)	72.3/65.6	0.355	16.1/32.8	0.011
	REALIZEb	60	31(52)/29(48)	48.4/41.4	0.586	19.4/13.8	0.563

^atreatment naive and relapse group; ^b NR-group (nonresponders, viral breakthrough and early discontinuation)

SVR=Sustained Virological Response; SAE= Serious Adverse Event; WQ=would qualify for trial; WNQ=would not qualify for trial

Conclusion: Patients in clinical practice are likely to not qualify for phase 3 trials and these patients are at higher risk for developing serious adverse events. Phase 3 trials should extend eligibility criteria to increase generalizability to clinical practice. Physicians should be aware that first generation protease inhibitors have worse safety profile and decreased effectiveness (boceprevir) in patients that would not qualify vs. patients that would qualify for clinical trials.

Disclosure of Interest: F. Berden: None declared, R. de Knegt Financial support for research: BMS, Roche, Janssen, Lecture fee(s): AbbVie, BMS, Gilead, Roche, Norgine, Consultancy: AbbVie, BMS, Gilead, Norgine, J. den Hollander: None declared, M. van Vonderen: None declared, P. Friederich: None declared, B. van Hoek Consultancy: Janssen-Cilag, Gilead, BMS, MSD, K. van Nieuwkerk: None declared, J. Drenth Financial support for research: AbbVie, Falk, Ipsen, Novartis, Zambon, Consultancy: AbbVie, Gilead, Janssen, BMS, W. Kievit: None declared

P0044 DOES NORMAL ALT MEAN HEALTHY LIVER IN HCV INFECTION ?

G. Par¹, H. Hajdu¹, A. Vincze¹, A. Miseta², A. Par¹

¹First Department of Medicine, ²Department of Laboratory medicine, University of Pecs, Pecs, Hungary

Contact E-mail Address: pargabriella@gmail.com

Introduction: HCV carriers with persistently normal ALT (PNALT) have usually mild and stable liver disease with favourable prognosis than patients with elevated ALT. However, several studies reported worsening of liver injury in 20-30% of subjects with PNALT and development of cirrhosis and even HCC. Aim of our study was to compare liver fibrosis stage and fibrosis progression in chronic hepatitis C (CHC) patients with ALT levels within normal limits and CHC patients with elevated ALT.

Aims & Methods: Aim of our study was to compare liver fibrosis stage and fibrosis progression in chronic hepatitis C (CHC) patients with ALT levels within normal limits and CHC patients with elevated ALT. Patients: Eighty-eight CHC patients were followed up in a five-year period. Fifty-three patients (60%) had ALT levels above our laboratory normal limit (ULN: >50 Iu/ml), 35 patients (40%) had normal ALT. Liver fibrosis (F0-F4 stages) were assessed by measuring liver stiffness (LS) using transient elastography (Fibroscan).

Results: Female CHC patients had normal ALT more often than males (44% vs. 34%). Out of 35 CHC patients with normal ALT fifteen (49%) had no or only mild liver fibrosis (LS <6 kPa). In the group of patients with elevated ALT, 17% had F0 or F1 liver fibrosis stage. Advanced liver fibrosis (LS > 12 kPa) was more frequent in patients with elevated ALT compared to normal ALT group (56% vs 23%). Although moderate or more severe liver fibrosis occured more frequently in patients with elevated ALT compared to normal ALT group (83% vs 51%), high proprotion of patients with normal ALT had LS suggesting moderate (>F1) fibrosis stage. In a five-year follow-up period most of the CHC patients with normal ALT had stable liver disease with no fibrosis progression.

Conclusion: Our results prove that normal ALT in CHC does not always mean “healthy liver” since a great proportion of these patients had minimal or moderate liver fibrosis and the possibility of progression to more severe condition. We do suggest that patients with normal ALT should not be excluded a priori from antiviral treatment. Decision on antiviral treatment should depend on multiple factors (e.g. histology, LS, symptoms, co-morbidities) as well as the motivation and the age of the patient, rather than on ALT level alone.

Disclosure of Interest: None declared

P0045 IS OLDER AGE A RISK FACTOR FOR HEPATOCELLULAR CARCINOMA DEVELOPMENT IN PATIENTS WITH CHRONIC HEPATITIS C EVEN IF SUSTAINED VIRUS ERADICATION IS REACHED?

G. Sirin¹, O. Sentürk², A. Celebi², M. Sezikli¹, H. Yılmaz², S. Hulagu²

¹Gastroenterology, Derince Education and Research Hospital, ²Gastroenterology, Kocaeli University, Kocaeli, Turkey

Contact E-mail Address: gsirin@live.com

Introduction: Hepatitis C virus (HCV) is one of the major leading causes of hepatocellular carcinoma (HCC) in Turkey. We aimed to clarify the clinical features of patients with chronic hepatitis C who develop HCC after gaining sustained viral response (SVR) to interferon (IFN)-based treatment.

Aims & Methods: Clinical parameters of 212 patients (mean age: 54 years old, E/K: 132/80) who achieved a SVR from 2002 to 2014 in two reference center hospital were evaluated.

Results: Eighteen patients (8.49%) developed HCC within a median follow-up period of 74 months (range 18–132 months). Cox regression analysis showed that the strongest predictive factor of HCC occurrence was lower platelet (<10x10⁴ cells/microL) count (hazard ratio [HR] 5.42, P=0.032) followed by prolonged (<80%) prothrombin time (HR 3.68, P=0.041) and higher AST (> 50 IU/L) level, (HR 3.18, P=0.048), before IFN therapy. At the time of SVR24, the predictive factors of HCC occurrence were higher AFP (>10 ng/ml) level (HR 4.33, P=0.028) and older (>65 years) age (HR 4.40, P=0.032). In multivariate analysis showed that higher AFP (>10 ng/ml) level and older (>65 years) age at SVR24 were independent variables of the development of HCC, too.

Conclusion: Patients of older (>65 years old) age at SVR24 should be considered very carefully to detect early HCC development after IFN therapy, especially who have higher AFP level, even if SVR is reached. In patients with chronic HCV, viral eradication of HCV infection should be achieved at a young age as possible to prevent HCC development after IFN based therapy.

Disclosure of Interest: None declared

P0046 FEASIBILITY AND REPRODUCIBILITY OF LIVER STIFFNESS (LSM) BY ELASTPQ POINT SHEAR-WAVE ELASTOGRAPHY

A. Baccarin¹, M. Fraquelli², G. Casazza³, C. B. Conti⁴, R. Pozzi¹, S. Massironi¹, A. Aghemo⁵, F. Donato⁵, D. Conte⁴, M. Colombo⁵

¹Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ospedale Maggiore Policlinico, Milan, ²Gastroenterology and Endoscopy Unit, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ospedale Maggiore Policlinico, ³Biomedical and Clinical Sciences , L. Sacco,” Università degli Studi di Milano, ⁴Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ospedale Maggiore Policlinico, ⁵Gastroenterology and Hepatology Unit, Fondazione IRCCS Ospedale Maggiore Policlinico, Milan, Italy

Contact E-mail Address: alessandra85.baccarin@gmail.com

Introduction: Liver stiffness measurement (LSM) by transient elastography (TE) accurately predicts severity of chronic liver disease (CLD). (1-2) Point quantification shear-wave elastography (pSWE-ElastPQ) is a newly developed technique incorporated into a conventional US system which allows evaluation of LSM.

Aims & Methods: Aim of this study was to assess the feasibility and reproducibility of PSWE-ElastPQ in a consecutive series of patients with CLD who concomitantly underwent TE and liver biopsy. Over a sixteen-months period, 164 patients (103 males, 61 females) (mean age 54 yrs) were consecutively enrolled. CLD was related to HCV (n=113) and miscellaneous causes (n=51). pSWE- ElatPQ was blindly performed by two raters whereas TE was performed by one single operator. pSWE-ElastPQ examinations were considered reliable if >10 validated measurements were obtained from each patient with SD <30% of the mean value. TE examinations were considered reliable if >10 validated measurements were obtained from each patient with a success rate >60% and if the interquatile range (IQR) was <30% of the median value. Interobserver agreement for pSWE-ElastPQ was analyzed using the intraclass correlation coefficient (ICC), that was interpreted according to Fleiss classification: agreement was considered poor (ICC=0.00-0.40), fair to good (ICC=0.40-0.75) or excellent (ICC < 0.75). Stage of liver fibrosis was classified according to METAVIR score classification.

Results: Reliable LSM (n=328)determinations were obtained in 100% of the cases by pSWE-ElastPQ and in 97% by TE (n=5 with SR <60%, IQR > 30%). pSWE-ElastPQ and TE values correlated significantly (r=0.68, p=0.0001). LSM values (mean ± SD, median) measured by pSWE-ElastPQ resulted 7.9 ± 4.4, 6.6 kPa for the first rater and 7.7 ± 4.0, 6.6 kPa for the second one. ICC concordance was not influenced by age, BMI, ALT, alkaline phosfatase and GGT levels. ICC in the first 5-months study period was significantly lower (0.69, 95% CI 0.50-0.81) as compared to the second period (0.78, 95% CI 0.64-0.87) and the third one (0.89, 95% CI 0.80-0.95).

Conclusion: pSWE-ElastPQ is a reliable and reproducible technique, whose interobserver agreement significantly improves by experience. Moreover it is not affected by BMI or presence of liver necroinflammation.

Disclosure of Interest: None declared

P0047 POINT SHEAR WAVE ELASTOGRAPHY (ELAST-PQ) FOR SPLEEN STIFFNESS (SSM) DETERMINATION IS FEASIBLE AND REPRODUCIBLE IN MOST OF THE PATIENTS WITH CHRONIC LIVER DISEASE

C. B. Conti¹, M. Fraquelli¹, A. Baccarin¹, G. Casazza², A. Zilli¹, F. Invernizzi³, F. Donato³, A. Aghemo³, D. Conte¹, M. Colombo³

¹Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ospedale Maggiore Policlinico, Università degli Studi di Milano, ²Department of Biomedical and Clinical Sciences , “L. Sacco,” Università degli Studi di Milano, ³Gastroenterology and Hepatology Unit, Fondazione IRCCS Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy

Contact E-mail Address: benedetta.conti1@gmail.com

Introduction: Spleen stiffness measurement (SSM) using transient elastography (TE) has widely been demonstrated to predict liver disease severity and progression of chronic liver disease (CLD) [1 - 3]. Its reliability and accurately predicts portal hypertension, oesophageal varices and such clinically relevant outcomes as decompensation [4]. Point quantification shear-wave elastography (pSWE-ElastPQ) is a newly developed technique to measure SSM incorporated into a conventional US system.

Aims & Methods: To assess feasibility and reproducibility of SSM by pSWE-ElastPQ in a consecutive series of patients with CLD who concomitantly underwent spleen TE and liver biopsy.

Over a 16-month period 160 patients were consecutively enrolled. Three were excluded due to previously splenectomy, thus 157 patients (99 males and 58 females; median age 55 years) were analysed.

CLD was HCV related in 109 and miscellaneous in 51. pSWE-ElastPQ was blindly performed by two different raters whereas TE was performed by a single operator. Both pSWE-ElastPQ and TE examinations were considered reliable if >10 validated measurements were obtained from each patient. SD of all measurement was < 30% of the mean value for pSWE-ElastPQ, whereas a success rate >60% and an interquartile range (IQR) of all validated measurements <30% of the median value were considered for TE.

Interobserver agreement for pSWE-ElastPQ was analyzed using the intraclass correlation coefficient (ICC), according to Fleiss classification: was considered poor (ICC=0.00-0.40), fair to good (ICC= 0.40-0.75) or excellent (ICC > 0.75).

Results: Reliable SSM determinations were more frequently obtained by pSWE-ElastPQ (155 cases; 96%) than by TE (141, 87%) (p=0.007) . pSWE-ElastPQ and TE SSM values correlated significantly (r=0.54 , p=0.0001). SSM values (mean ± SD, median) measured by pSWE-ElastPQ resulted 17.8 ± 8.6, 15.7 kPa for the first rater and 17.6 ± 8.3, 15.6 kPa for the second one. Overall, interobserver ICC for pSWE-ElastPQ was 0.72, 95% (CI 0.64-0.79). Concordance was not influenced by patient’s age, sex and BMI. The ICC in the first 10-months study period was significantly lower (0.69, 95% CI 0.58-0.79) as compared to the second 6 months (0.86, 95%CI 0.75-0.93)

Conclusion: pSWE-ElastPQ is a reliable and reproducible technique to assess spleen stiffness in CLD, whose interobserver agreement significantly improves by experience. Noteworthy, pSWE-ElastPQ is feasible in more patients than TE.

Disclosure of Interest: None declared

P0048 ULTRASOUND DIAGNOSTICS SIMULATORS FOR GASTROENTEROLOGISTS: IMPLEMENTATION EXPERIENCE

D. Venidiktova¹, A. Borsukov¹

¹Smolensk State Medical University, Problem scientific-researh laboratory “Diagnostic researches and miniinvasive technologies", Smolensk, Russian Federation

Contact E-mail Address: darya.venidiktova@gmail.com

Introduction: Nowadays various types of hospitals and clinics require professional specialists in ultrasound diagnostic not only among radiologists, but also among clinicians to ensure fast and correct diagnosis for adequate treatment prescribing. Unfortunately there is no opportunity for all specialists to have education by the standard scheme “mentor-specialist in training-patient” because of limited time, so there is a necessarity to put inexpensive and available for clinicians ultrasound simulators into training-practice.

Aims & Methods: The aim was to create the experimental model of Doppler ultrasound simulation system which will be able to imitate arterial and venous blood flow and focal lesions of parenchymal organs with various type of vascularization for the gastroenterologists ultrasound education.

Material and methods: Vascular phantom was created in our Problem scientific research Laboratory “Diagnostic researches and miniinvasive technologies” in 2014. It represents tube system and consists of two parts. The 1st part is vascular - with imitative characteristics of arterial and venous blood flow (with the opportunity of laminar and turbulent flow recreation, using semi-automatic dispenser). The 2nd part is “pathological foci", it represents hemodynamics of capillary and cavernous hemangioma, focal nodular hyperplasia and hyper-vascular liver metastases. There were 2 groups of 6-year medical students of Smolensk State Medical University with 20 in each group for the Phantom's efficiency testing. Educational process in the 1st group was by the standard scheme “mentor-student-patient” (3 times). Educational process in the 2nd group consisted of 2 stages: at the 1st stage all of the students had practice with the ultrasound simulator and at the 2nd stage there was standard scheme “mentor-student-patient” (3 times).

Results: After 3-weeks of training all of the students were tested in real work with patients with arterial blood flow pathology (aneurysm, n=4), venous blood flow pathology (cavernous portal vein transformation at cirrhosis n=8, capillary and cavernous hemangioma, n=13, focal nodular liver hyperplasia n=2, colorectal liver metastases, n=4). In the 1st group true-positive results amounted 58.1%, false-positive results - 24.4%, false-negative results - 17.5%. In the 2nd group true-positive results amounted 79.3%, false-positive results - 13.9%, false-negative results - 6.8%.

Conclusion: Phantom's use at the 1st stage of gastroenterologists education in ultrasound technique qualitatively improved the efficiency of medical specialists' work, so it requires overall introduction of simulator-training in courses of postgraduate professional education.

Disclosure of Interest: None declared

P0049 GASTROINTESTINAL NEUROENDOCRINE TUMORS OF UNKNOWN PRIMARY SITE: REPORT FROM A SERIES AT A SINGLE INSTITUTE

S. Massironi¹, I. Fanetti¹², F. Cavalcoli¹², A. Zilli¹², D. Conte¹²

¹Gastroenterology and Endoscopic Unit, Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico , ²Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy

Contact E-mail Address: cavalcoli.federica@gmail.com

Introduction: Neuroendocrine neoplasms (NENs), a heterogeneous group of neoplasms, differ in biologic behavior, histologic appearance and response to treatment. NENs with unknown primary site (NENs-UP) account for 10 to 13 percent of all NENs.

Aims & Methods: We here describe clinical findings, histologic and anatomic characteristics and the diagnostic work-up of patients with histologically proven metastatic NENs of unknown primary.

Between January 2005 to January 2015, of the 93 patients with metastatic gastrointestinal NENs seen at our Institution, 17 (18%) (M:F = 11:6; median age at the diagnosis 64 years, range 33-74) presented with immunohistochemically proven neuroendocrine metastases without evidence of primary site despite an exhaustive work-up based on computed tomography (CT), magnetic resonance (MRI) and somatostatin receptor scintigraphy (SRS).

Results: Of the 17 patients with NENs-UP, 14 (82%) showed hepatic metastases, whereas an abdominal nodal involvement was detected in the other three patients. Sixteen of the 17 tumors (88%) were well differentiated (G1 in five cases and G2 in 11), with a poorly differentiated carcinoma in the last patient. Carcinoid, Zollinger-Ellison and Verner-Morrison syndromes were diagnosed in eight, two and one case, respectively, accounting for a total number of 11 functioning tumors (65%). In 14 of the 17 cases (82%), liver or nodal metastases were firstly diagnosed by abdominal ultrasound, performed during surveillance of chronic diseases in six patients and for gastrointestinal symptoms in the other eight. In the course of a strict work-up, the primary tumor was eventually diagnosed after a median of 8.5 months (range 3-120) in 12 cases (71%), eight of whom (67%) had a functioning form. In detail, the primary site was identified as pancreas by a repeated abdominal CT (#3); terminal ileum (#2) and colon (#1) by colonoscopy; central ileum by double balloon enteroscopy (#1) and pancreas by endoscopic ultrasound (EUS) (#1). Again, laparoscopy identified a jejunal, ileal, Meckel's diverticulum and pancreatic primary tumor in further four patients, whereas the remaining five were still classified as NENs-UP.

Conclusion: NENs-UP represent a clinical challenge, involving multidisciplinary expertise. Despite the continuous advances in diagnostic techniques, including radiologic, endoscopic and immunohistochemical methods, metastatic NENs remain of unknown primary origin in a notable proportion of cases (5/93, 5.3% in present series), even after an in-depth work-up. Noteworthy, however, the presence of hormone-related symptoms may help to better localize the primary site.

Disclosure of Interest: None declared

P0050 COMPARATIVE STUDY BETWEEN FOUR ULTRASOUND SHEAR WAVE ELASTOGRAPHIC METHODS FOR LIVER STIFFNESS ASSESSMENT

I. Sporea¹

¹Gastroenterology and Hepatology, University of Medicine and Pharmacy Victor Babes Timisoara, Timisoara, Romania

Contact E-mail Address: isporea@umft.ro

Introduction: Many different types of ultrasound based elastographic methods have been developed for the non-invasive liver stiffness assessment.

Aims & Methods: The aim of this study was to compare the performances of the latest elastographic methods used for liver fibrosis evaluation (Point Shear Wave Elastography-PSWE using ARFI technique-VTIQ and ElastPQ, respectively; and SuperSonic Shear Imaging-2D-SWE) considering Transient Elastography (TE) the reference method, since TE is a validated method for liver fibrosis evaluation.

The study included 151 consecutive subjects with or without chronic hepatopathies (excluding patients with ascites), in which liver stiffness (LS) was evaluated in the same session by means of 4 elastographic methods: TE (FibroScan, Echosens), VTIQ (Siemens Acuson S2000™), ElastPq (Philips, Affinity) and 2D-SWE (Aixplorer™SuperSonic Imagine S.A). Reliable LS measurements were defined as follows: for TE and VTIQ–the median value of 10 LS measurements with a success rate ≥ 60% and an interquartile range < 30%, for 2D-SWE–the median value of 3 LS measurements acquired in an homogenous area and for ElastPQ-the median value of 10 LS measurements.

LS was expressed in kPa for TE, 2D-SWE, ElastPQ and m/s for VTIQ . For differentiating between stages of liver fibrosis we used the following cut-off values: for TE-significant fibrosis (F ≥ 2)–7.2 kPa and for liver cirrhosis (F4)-14.5kPa (Tsochatzis, 2011); for VTIQ: F ≥ 2–1.35m/s, F4=1.84m/s (Nierhoff, 2013); for 2D-SWE F ≥ 2–7.1 kPa, and F4=13.5 kPa (HCV,NAFLD) and 11.5 kPa in HBV (Herrmann, 2015); and for ElastPQ F ≥ 2-5.9 kPa, F4=12kPa (Ferraioli, 2013).

Results: Considering TE as the reference method, the diagnostic accuracy of VTIQ, 2D-SWE and ElastPQ for the diagnose of absence or mild fibrosis (F < 2) was similar: VTIQ vs. 2D-SWE (86.2% vs. 82.5% p=0.57); VTIQ vs. ElastPQ (86.2% vs. 84.4% p=0.85), 2D-SWE vs. ElastPQ (82.5% vs. 84.4% p=0.84).

For significant fibrosis (F ≥ 2) the values obtained were: VTIQ vs. 2D-SWE (84% vs. 76.1% p=0.19); VTIQ vs. ElastPq (84% vs. 80.7% p=0.64), 2D-SWE vs. ElastPq (76.1% vs. 80.7% p=0.50).

For diagnosing cirrhosis we obtained similar diagnostic accuracies: VTIQ vs. 2D-SWE (96.3% vs. 93.6% p=0.54); VTIQ vs. ElastPQ (96.3% vs. 94.5% p=0.75), 2D-SWE vs. ElastPQ (93.6% vs. 94.5% p=0.99).

Conclusion: Considering TE as the reference method for liver fibrosis evaluation, VTIQ, ElastPQ and 2D-SWE had similar accuracies for diagnosing at least significant fibrosis (F ≥ 2) and liver cirrhosis.

Disclosure of Interest: None declared

P0051 FEASIBILITY OF FOUR ULTRASOUND SHEAR WAVE ELASTOGRAPHIC METHODS FOR LIVER STIFFNESS ASSESSMENT

I. Sporea¹, R. Mare¹, O. Gradinaru Tascau¹, A. Popescu¹, R. irli¹

¹Gastroenterology and Hepatology, University of Medicine and Pharmacy Victor Babes Timisoara, Timisoara, Romania

Contact E-mail Address: isporea@umft.ro

Introduction: In the last decade , different types of ultrasound-based elastographic methods that non-invasively quantify liver fibrosis, have been developed. Even though Transient Elastography is a validated method for liver fibrosis assessment in chronic B and C hepatitis, being included in EASL Guidelines, reliable elasticity measurements are difficult to obtain in obese (BMI > 30kg/m²) patients.

Aims & Methods: The aim of this study was to compare the feasibility of four elastographic methods used for liver fibrosis evaluation (Transient Elastography-TE, Point Shear Wave Elastography (PSWE) using ARFI technique -VTIQ and ElastPQ and SuperSonic Shear Imaging-2D-SWE).

The study included 151 consecutive subjects with or without chronic hepatopathies (excluding patients with ascites), in which liver stiffness (LS) was evaluated in the same session by means of 4 elastographic methods: TE (Fibroscan, Echosens), VTIQ (Siemens Acuson S2000™), ElastPQ (Philips, Affinity) and 2D-SWE (Aixplorer, SuperSonic Imagine S.A). Reliable LS measurements were defined as follows: for TE and VTIQ¹ – the median value of 10 LS measurements with a success rate ≥ 60% and an interquartile range < 30%, for 2D-SWE² – the median value of 3 LS measurements acquired in an homogenous area and for ElastPQ- the median value of 10 LS measurements. For TE M and XL probes are used. LS was expressed in kPa for TE, 2D-SWE, ElastPQ and m/s for VTIQ. All elastographic measurements were performed by experienced operators.

Results: Reliable LS measurements were obtained in a significantly higher proportion of patients by means of ElastPQ as compared with TE, 2D-SWE and VTIQ: 99.3% vs. 87.4% (p < 0.0001), 99.3% vs. 87.4% (p < 0.0001) and 99.3% vs. 92.7% (p=0.08). TE and 2D-SWE had similar rates of reliable LS measurements 87.4% vs. 87.4% (p=0.86).

Reliable LS measurements by all four shear waves ultrasound elastographic methods were obtained in 72.2% (109/151 subjects).

Comment: No study concerning the usefulness of technical quality criteria for ElastPQ was published.

Conclusion: ElastPq elastography was the most feasible shear-waves elastographic method for liver fibrosis assessment, followed by VTIQ, while TE and SSI had similar rates of reliable LS measurements.

Disclosure of Interest: None declared

P0052 INTERSTITIAL CAJAL-LIKE CELLS/TELOCYTES AND GALLBLADDER AUTONOMIC NERVOUS SYSTEM INTERPLAY IN THE PATHOGENESIS OF CHOLELITHIASIS

A. Pasternak¹, M. Szura², A. Matyja², M. Kurnik³, J. Walocha¹, K. Gil³

¹Anatomy, ²1st Chair of General Surgery, ³Pathophysiology, Uniwersytet Jagielloński - Collegium Medicum, Kraków, Poland

Contact E-mail Address: artpast@tlen.pl

Introduction: The major mechanisms of gallstone formation include biliary cholesterol hypersecretion, supersaturation and crystallization, mucus hypersecretion, gel formation and bile stasis. Gallbladder hypomotility seems to be a key event that triggers the precipitation of cholesterol microcrystals from supersaturated lithogenic bile. Recently, we reported a significant decrease in interstitial Cajal-like cell (ICLC) density in gallbladders of patients with cholelithiasis. Such cells in the gallbladder were strongly influenced by lithogenic bile. ICLCs, as well as the autonomic neurons located within gallbladder muscularis propria are considered as predominant regulatory cells of gallbladder motility.

Aims & Methods: The purpose of the current study was to determine the influence of lithogenic bile on the gallbladder autonomic neurons, in relationship to ICLCs. Gallbladder specimens were collected from 20 patients (8 males and 12 females) who underwent elective laparoscopic cholecystectomy for symptomatic gallstone disease. The control gallstone-free group consisted of 20 consecutive patients (9 males and 11 females) who received elective treatment for pancreatic head tumors. ICLCs were visualized in paraffin sections of gallbladders with double immunofluorescence using primary antibodies against c-Kit (anti-CD117) and anti-mast cell tryptase. The telocytes were stained with anti-CD34 antibody and assessed simultaneously. Autonomic neurons within the gallbladder wall were visualized by immunohistochemistry using anti-PGP9.5, anti-ChAT and anti-NOS antibodies and assessed semi-quantitatively. Cholesterol, phospholipid and bile acid concentrations were measured in bile samples obtained by needle aspiration from the gallbladder during surgery.

Results: The number of ICLCs in the gallbladder wall was significantly lower in the study group than in the control group (3.2 ± 1.5 vs. 6.6 ± 1.8 cell/area of view in the muscularis propria, P < 0.001) and correlated with a significant increase in the cholesterol saturation index, so did the telocytes count. The glycocholic and taurocholic acid levels were significantly elevated in the control subjects compared with the study group. Numerous PGP9.5-positive neural fibers were present, including some neuron bodies. Only sparse cholinergic (ChAT-positive) as well as nitrergic (NOS-positive) neurons were found. The cumulative neurons count was slightly decreased in patients with gallstones.

Conclusion: These results suggest that bile composition plays an important role in the reduction of ICLC and autonomic neurons density in the gallbladder, and this might lead to the gallbladder dysmotility in patients with cholelithiasis.

Disclosure of Interest: None declared

P0053 SCORING SYSTEM IN ALGORITHM FOR DIAGNOSIS AND TREATMENT OF PATIENTS WITH A SPHINCTER OF ODDI DYSFUNCTION

M. V. Repin¹, A. V. Popov¹, V. Y. Mikryukov², T. E. Vagner²

¹Perm State Medical University named after E.A. Vagner, ²Perm regional clinical hospital, Perm, Russian Federation

Contact E-mail Address: max_repin@inbox.ru

Introduction: It is difficult to exclude organic pathology, to choose a proper sequence for examination and treatment of patients with a suspected sphincter of Oddi dysfunction (SOD).

Aims & Methods: To develop diagnostic and medical algorithm for patients with a suspected SOD on the basis of integral estimation of clinical, laboratory and instrumental studies. Multifactor analysis performed in 164 patients after cholecystectomy permitted to single out and express in scores the most significant estimation signs. Typical hepatic colic scored 3; arrested colic – 2 scores, uncertain pains in the right hypochondrium – 1 score; jaundice – 2 scores, jaundice in anamnesis – 1 score; moderate rise in transferases – 1 score; 2-4 fold rise – 2 scores, more than four-fold rise – 3 scores; increase in total bilirubin: up to 40 mcmol/l – 1 score, 40-100 mcmol/l – 2 scores, more than 100 mcmol/l – 3 scores; elevation in serum α-amilase by 1.5-2 times – 1 score; increase in alkaline phosphatase – 1 score; increase in total blood leukocyte number: 9-12 thousand – 1 score, more than 12 thousand – 2 scores; the common bile duct dilatation by TUS data: from 7-12 mm – 1 score, from 13-22 mm – 2 scores, more than 22 mm – 3 scores. Peculiarities of bile outflow were estimated by the results of hepatobiliary scintigraphy (HBSG). In case of doubtful diagnosis, computed tomography, magnetic resonance cholangiopancreatography and/or retrograde cholangiopancreatography were used.

Results: By the developed scoring system, patients were divided into 4 groups. Accordance of this gradation to III Roman classification for patients with SOD was established. In group 1, 60 patients had 4 and more scores (5.1 ± 1.8). HBSG was performed only in 5 (8.3%) patients and bile outflow was delayed in all cases. Later on, choledocholithiasis (CL) was detected in 32 patients, Oddi’s sphincter stenosis – 28. All patients underwent surgery. In group 2, in 31 patients the sum of scores varied from 3 to 4 (3.1 ± 0.3) and was lower than in group 1 (p < 0.05). 21 patients experienced HBSG, in most cases bile outflow was normal and only in 2 patients bile flow was delayed. Further, CL was diagnosed in 3 patients, Oddi’s sphincter stenosis – 2. They underwent papillotomy (PT) with lithoextraction (LE). Group 3 enclosed 63 patients with the sum of scores varying from 1 to 2 (1.5 ± 0.5). In all the cases with HBSG accelerated bile outflow, considered by us as Oddi’s sphincter insufficiency, was stated. However, 2 patients were diagnosed CL that became an indication for PT and LE. Group 4 included 10 patients with increase in serum α-amilase. The sum of scores varied from 1 to 3 (2.5 ± 0.5). In all cases with HBSG accelerated bile outflow, as in group 3, was noted. No operative interventions were required in this group.

Conclusion: The developed algorithm for patients with suspected SOD facilitates determination of the sequence of studies and the choice of management. A four-score excess by the estimation sign scale can serve as a reason for invasive studies and surgery. Use of HBSG permits to assess noninvasively the status of bile outflow that is not impaired in most cases but even accelerated. Oddi’s sphincter insufficiency can be an independent type of functional disorders which should be taken into consideration when choosing management tactic.

Disclosure of Interest: None declared

P0054 RIP3 KINASE CONTRIBUTES TO NECROINFLAMMATION IN THE CHOLESTATIC LIVER

M. B. Afonso¹, P. M. Rodrigues¹, A. L. Simão¹, H. Cortez-Pinto²³, D. Ofengeim⁴, J. D. Amaral¹, R. E. Castro¹, J. Yuan⁴, C. M. P. Rodrigues¹

¹Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, ²Gastrenterology, Hospital Santa Maria, ³Faculty of Medicine, Universidade de Lisboa, Lisbon, Portugal, ⁴Department of Cell Biology, Harvard Medical School, Boston, MA, United States

Contact E-mail Address: mbafonso@ff.ulisboa.pt

Introduction: Cholestasis is associated with liver inflammation and hepatocyte damage, through incompletely understood pathophysiological processes. The kinase activity of receptor interacting protein 3 (RIP3) plays an important role in necroptosis, a novel immunogenic cell death type that may contribute to inflammation-driven liver diseases.

Aims & Methods: Here we aimed to evaluate the role of necroptosis after common bile duct ligation (BDL) in mice, a classic experimental model for acute cholestasis and secondary biliary fibrosis, and in patients with primary biliary cirrhosis (PBC), a cholestatic chronic liver disease.

BDL or sham surgery was performed in C57BL/6 wild-type (WT) or RIP3 knockout (KO) mice. Serum and livers were collected 3 and 14 days after BDL. Histology, serum liver enzymes and bilirubin were evaluated. Liver RIP3, proinflammatory cytokines and fibrosis markers were determined by qRT-PCR. Total and soluble/insoluble liver proteins were analysed by Western blot. RIP3 kinase activity was determined in vitro. The functional crosstalk between RIP3 and antioxidant responses was investigated. Finally, RIP3 and phosphorylated mixed lineage kinase domain-like protein (p-MLKL) were evaluated by immunohistochemistry in liver specimens of patients with PBC and healthy controls.

Results: In WT mouse livers, BDL resulted in bile duct hyperplasia, multifocal necrosis, fibrosis and inflammatory cell infiltration. Concomitantly, necroptosis was activated as assessed by: 1) sequestration of RIP3 and its target MLKL in the insoluble protein fraction of the liver; 2) increased RIP3 kinase activity; and 3) increased RIP3 mRNA and protein expression (at least, p < 0.05). Remarkably, histological analysis revealed that RIP3 deficiency significantly decreased liver necrosis and inflammation induced by BDL at both 3 and 14 days (p < 0.05). At day 3, but not at day 14, BDL RIP3 KO mice showed lower circulating levels of hepatic enzymes, decreased inflammatory and fibrogenic liver gene expression, and enhanced antioxidant responses (at least, p < 0.05). Finally, RIP3 and p-MLKL expression was induced in PBC patients (p < 0.05).

Conclusion: In conclusion, RIP3-dependent signaling is triggered in human PBC and mediates hepatic necroinflammation in BDL-induced acute cholestasis. As such, targeting RIP3-dependent pathways may provide an unprecedented opportunity to develop novel therapeutic strategies to ameliorate cholestatic liver injury, although complementary approaches may be required to control progression to fibrosis.

Supported by PTDC/SAU-ORG/119842/2010, HMSP-ICT/0018/2011 and SFRH/BD/91119/2012, from FCT, Portugal.

Disclosure of Interest: None declared

P0055 THE SHORT- AND LONG-TERM OUTCOMES OF SUBTOTAL CHOLECYSTECTOMY: A REVIEW OF 190 PROCEDURES

A. Van Dijk¹, S. Donkervoort², W. Lameris³, Q. Eijsbouts³, B. Vrouenraets⁴, O. Busch¹, M. Boermeester¹, P. de Reuver⁵

¹Surgery, Academic Medical Center, ²Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, ³Surgery, Spaarne Gasthuis, Hoofddorp, ⁴Surgery, Sint Lucas Andreas Ziekenhuis, Amsterdam, Netherlands, ⁵Surgery, Royal North Shore Hospital, Sydney, Australia

Contact E-mail Address: a.h.vandijk@amc.nl

Introduction: Complicated cholecystolithiasis occurs in about a third of all patients with gallstones and is frequently associated with a difficult cholecystectomy with unclear anatomy. Several techniques to safely remove the gallbladder in these patients exist, including a subtotal cholecystectomy (SC).

SC is reported to be safe and feasible, but an increase in bile leaks and retained gallstones have also been described.

The objective of this study was to assess the short- and long-term outcomes following SC.

Aims & Methods: A retrospective review of all patients who received cholecystectomy in 3 hospitals (from January 2003 to October 2013) in the Netherlands was performed. Patients who underwent SC were identified based on operative reports. Patient characteristics, operative details and the short and long term outcomes were recorded from patients files.

Short-term outcome was defined as the occurrence of bile duct injuries, intra-abdominal abcesses, biloma’s, woundinfections and the rate of readmittance and reinterventions. The completion of the cholecystectomy and the occurrence of bile duct strictures were considered long-term outcomes.

Results: A total of 5155 operative records were screened, of which 190 were SC (3.7%). A third of patients (n=56, 30%) had SC for symptomatic uncomplicated cholelithiasis. The remaining patients were diagnosed with complicated cholelithiasis, of whom 72 patients (38%) had acute cholecystitis. Short-term total morbidity was 34.2% (n=65). A total of 25 patients (13.2%) were diagnosed with a bile duct injury, of which 24 patients solely had a leakage of the cystic duct. In only one patient an injury to the common bile duct (0.5%) was seen. An ERC was necessary in 41 patients, mostly due to persistent bile leakage (9.5%) or common bile duct stones (11.1%). In the long-term a bile structure was seen in only 1 patient (0.5%) and 20 patients (10.5%) underwent a completion of the cholecystectomy with an associated morbidity of 30%.

Conclusion: Subtotal cholecystectomy is an effective strategy to circumvent severe bile duct injury and bile strictures, but the risk is transferred to cystic duct leakage in 1 out of 10 patient and associated postoperative morbidity.

Disclosure of Interest: None declared

P0056 THE COMPARISONS BETWEEN GENERAL ENDOTRACHEAL ANESTHESIA, AND NON-ANESTHESIA IN RETROGRADE EDOSCOPIC COMMON BILE DUCT STONE REMOVAL IN THE REAL WORLD

C.-M. Liang¹, C.-M. Kuo¹, W.-C. Tai¹

¹Division of Hepato-gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung, Taiwan, Province of China

Contact E-mail Address: gimy54861439@gmail.com

Introduction: In Asia, as well as in some European countries , South America, and the Middle East , conscious sedation is not used routinely for therapeutic endoscopic retrograde cholangiopancreatography (ERCP). However, conscious sedation may easily progress to anesthesia once verbal contact has been lost. Therefore, general anesthesia sedation is conducted for ERCP in our institution, but not moderate conscious sedation anesthesia.

Aims & Methods: We carried out a retrospective evaluation to analyze common bile duct stone extraction in ERCPs under non-sedation and general anesthesia, to determine the safety, successful rate, and complications in these two groups. In retrospectively reviewed study, all ERCPs with stone extraction under general anesthesia or non sedation from Jan, 2010 to Sep. 2013. The participants were aged 18 years and above. Criteria for exclusion: procedure failed due to anatomy change after operation, pyloric ring stenosis, and tumor related obstruction. Non sedation (NS) group: pethidine 40-50mg for pain control 10 minutes before papilloplastic balloon dilatation. General anesthesia (GET) group: general endotracheal anesthesia before ERCP. The definition of primary outcomes: success of stone removal (complete bile duct stone clearance), major complications (post ERCP pancreatitis (PEP) (amylase > 3times of upper limit level), perforation, bleeding, pneumonia in 30 days and mortality in 30 days). The operation time in ERCP was defined as cannulation starting time to complete stone removal.

Results: There are consecutive 166 patients enrolled. Eleven cases are excluded, 2 cases post whipple procedure, 2 case post Billroth II subtotal gastrectomy, 4 cases with stenting to stone obstruction, no attempt to remove. 2 cases with pyloric ring stenosis, one case failed to find papilla. There are 77 patients with NS method and 78 with GET for attempt to bile duct stone removal. Age, sex, personal habitats (alcohol, smoking), American Society of Anesthesiologists (ASA) score, previous ERCP experience, and comorbidities were similar in these two groups. Nine patients (11.5%) in NS group could not complete the procedure due to intolerance. Successful rate of complete stone extraction was higher in the GET (93.6%) versus in the NS (77.9%) group; p=0.005. The rate of post-ERCP pancreatitis (PEP) was higher in NS group versus the GET group (20.8% versus 10.3%; p=0.004). The operation time was shorter in NS group versus GET group(23.1 ± 10.1 versus 28.3 ± 13.7, p=0.023). The complication rate was similar between NS and GET groups (no bleeding case; perforation: 1.3% versus 0%, p=0.313; pneumonia: 2.6% versus 3.8%, p=0.660; mortality: 1.3% versus 1.3%, p=0.993). In multivariate analysis for the clinical factors influencing PEP, sedation group is a negative facotr for PEP (coefficient of variation: -1.23 ± 0.55, 95% C.I. 0.29(0.10∼0.86), p=0.026), and operation time (≥30mins) (coefficient of variation: 1.43 ± 0.57, 95% C.I. 4.20(1.36∼12.97), p=0.013)is a positive predisposing factor.

Conclusion: We conclude that ERCP under GET is safe and effective for common bile stone removal, with lower PEP rate than non-sedation patients.

Disclosure of Interest: None declared

P0057 RECURRENCE OF CHOLEDOCHOLITHIASIS FOLLOWING ENDOSCOPIC BILE DUCT CLEARANCE: LONG-TERM RESULTS AND FACTORS ASSOCIATED WITH RECURRENT BILE DUCT STONES

C. Konstantakis¹, K. Thomopoulos¹, V. Theopistos¹, G. Theoxaris¹, C. Triantos¹, G. Diamantopoulou¹

¹Department of Gastroenterology, University Hospital of Patras, Patras, Greece

Contact E-mail Address: asraiah@yahoo.com

Introduction: Recurrence of bile duct stones is a possibility following endoscopic extraction.

Aims & Methods: The aim of our study was to evaluate the rate of recurrence of symptomatic choledocholithiasis and to identify factors associated with the recurrence of bile duct stones in patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (ES) for bile duct stone disease.

Patients who underwent ERCP and ES for bile duct stone disease and had their bile duct cleared from 1/1/2005 until 31/12/2008 were enrolled. All symptomatic recurrences during the study period (until 31/12/2014) were recorded. Clinical and laboratory data potentially associated with common bile duct (CBD) stone recurrence were retrospectively retrieved from patients’ files.

Results: A total of 495 patients were included. Sixty seven (67) out of 495 patients (13.5%) presented with recurrent symptomatic choledocholithiasis after 39.2 ± 25.6 months (13-168 months) while twenty one (21) of these patients (31%) experienced a second recurrence after 9 – 78 months.

Factors associated with recurrence were the size (diameter) of the largest CBD stone found at first presentation (10.2± 6.9 mm vs 7.2± 4.1 mm p=0.024) and the diameter of the CBD at the first examination (15.5 ± 6.3 mm vs 12.0 ± 4.6 mm p=0.005). Number of stones at first presentation (3.9 ±4.3 vs 3.5 ±2.3), age or sex of the patient did not influence recurrence. Moreover oblique CBD angulation (calculated by measuring the angle enclosed between the horizontal portion of the CBD and the horizontal plane) was significantly associated with stone recurrence (43.4 ± 10 vs 50.5 ± 15 p=0.016).

Conclusion: Bile duct stone recurrence is a likely late complication following endoscopic stone extraction and CBD clearance. It appears to be associated with anatomical parameters (CBD diameter, angulation) and stone characteristics (stone size) at first presentation.

Disclosure of Interest: None declared

P0058 LIMITED PRECUT SPHINCTEROTOMY COMBINE ENDOSCOPIC PAPILLARY BALLOON DILATION TO TREAT DIFFICULT BILIARY CANNULATION WITH COMMON BILE DUCT STONES

C.-M. Kuo¹, C.-M. Liang¹, W.-C. Tai¹

¹Division of Hepato-gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung, Taiwan, Province of China

Contact E-mail Address: kuo51116@gmail.com

Introduction: Difficult biliary cannulation in endoscopic retrograde cholangiopancreatography (ERCP) causes the failure of common bile duct stones removal. Difficult biliary cannulation can also cause more post-ERCP complications (acute pancreatitis, biliary tract infection (BTI) and bleeding).

Aims & Methods: To evaluate the outcome and complications of limited precut sphincterotomy combined with endoscopic papillary balloon dilation (EPBD) to treat difficult biliary cannulation with common bile duct stones retrospectively. From Oct 2009 to Sep 2014 in CGMH, total 3305 patients received ERCP examination and treatment. Of all, 258 (7.8%) patients belonged to difficult biliary cannulation and 145 patients were difficult biliary cannulation with common bile duct stones. We performed limited precut sphincterotomy combined EPBD in 58 patients (M:28, F:30; age 64.02 ± 16.37 yr (26-96). The definition of difficult biliary cannulation in our study was: (1)10 min time limits for cannulation or (2) 5 passage or injection into pancreatic duct or (3) 10 attempts on the papilla without time limit. Limited sphincterotomy means the extent of needle knife cutting < 1/2 length of the papillary mound, then combined CRE balloon dilation (8-20 mm) with dilation time 2 minutes.

Results: Overall successful common bile duct (CBD) stones removal was 94.8% (55/58) and 1st session success was 87.9% (51/58). Mean procedure time was 41 ± 11.48 (20-72) min. Mean CBD size was 1.47 ± 0.44 (0.7-2.6) cm and mean stone size was 1.11 ± 0.40 (0.4-2.0) cm. CBD stone number with 1:2: ≥3 was 28:14:16. Need of mechanical lithotripsy (ML) was 10.3% (6/58). Post-treated complications were bleeding 3.4% (2/58), pancreatitis 8.6% (5/58) and BTI 2.7% (1/58). We analyzed and investigated the relationship of risk factors in published studies in post-treated bleeding and pancreatitis. Coronary artery disease (CAD), stroke, end-stage renal disease (ESRD), liver cirrhosis (LC), age > 70 yrs, distal CBD narrowing, and BTI were not statistically significant factors for post-treated bleeding. Sex, age < 60 yrs, jaundice, previous pancreatitis, lithotripsy, > 3 CBD stones, and CBD < 0.8 cm were not statistically significant factors for post-treated pancreatitis.

Conclusion: There was no significant post-treated duodenal bleeding (3.4%) compared to published studies in patients with post-endoscopic sphincterotomy (EST) (1-3%) or post-precut spincterotomy (2-2.7%) or post-EST + endoscopic papillary large balloon dilation (EPLBD) (5.2-10.3%). There was no significant post-treated pancreatitis (8.6%) compared to published studies in patients with difficult biliary cannulation (4.3-11.3%) or post-EPBD (5-15%) or post-EST + EPLBD (0-6%). Overall successful stone removal (94.8%) and reduced need for ML (10.3%) is similar to patients with EST + EPLBD (80-100% and 1-11%). Limited precut sphincterotomy combined with EPBD to treat difficult biliary cannulation with common bile duct stones is safe and effective.

Disclosure of Interest: None declared

P0059 ENDOSCOPIC ULTRASOUND VS MAGNETIC RESONANCE CHOLANGIOPANCREATOGRAPHY FOR COMMON BILE DUCT STONES. A SYSTEMATIC REVIEW

D. Ledro Cano¹, D. López Peñas¹

¹Gastroenterology, Hospital de Llerena, Llerena, Spain

Contact E-mail Address: diego.ledro@ses.juntaextremadura.net

Introduction: Endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography (MRCP) are tests used in the diagnosis of common bile duct stones in patients suspected of having common bile duct stones prior to undergoing invasive treatment.

Aims & Methods

Aims: To determine and compare the accuracy of EUS and MRCP for the diagnosis of common bile duct stones.

Methods: We searched MEDLINE, EMBASE, Science Citation Index Expanded, BIOSIS, and Clinicaltrials.gov until September 2012. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively.

We included studies that provided the number of true positives, false positives, false negatives, and true negatives for EUS or MRCP. We only accepted studies that confirmed the presence of common bile duct stones by extraction of the stones (irrespective of whether this was done by surgical or endoscopic methods) for a positive test, and absence of common bile duct stones by surgical or endoscopic negative exploration of the common bile duct or symptom-free follow-up for at least six months for a negative test, as the reference standard in people suspected of having common bile duct stones. At least two authors independently screened abstracts and selected studies for inclusion.

Two authors independently collected the data from each study. We used the bivariate model to obtain pooled estimates of sensitivity and specificity.

Results: We included a total of 18 studies involving 2366 participants (976 participants with common bile duct stones and 1390 participants without common bile duct stones). Eleven studies evaluated EUS alone, and five studies evaluated MRCP alone. Two studies evaluated both tests. For EUS, the sensitivities ranged between 0.75 and 1.00 and the specificities ranged between 0.85 and 1.00. The summary sensitivity (95% confidence interval (CI)) and specificity (95% CI) of the 13 studies that evaluated EUS (1537 participants; 686 cases and 851 participants without common bile duct stones) were 0.95 (95% CI 0.91 to 0.97) and 0.97 (95% CI 0.94 to 0.99). For MRCP, the sensitivities ranged between 0.77 and 1.00 and the specificities ranged between 0.73 and 0.99. The summary sensitivity and specificity of the seven studies that evaluated MRCP (996 participants; 361 cases and 635 participants without common bile duct stones) were 0.93 (95% CI 0.87 to 0.96) and 0.96 (95% CI 0.90 to 0.98). There was no evidence of a difference in sensitivity or specificity between EUS and MRCP (P value = 0.5). From the included studies, at the median pre-test probability of common bile duct stones of 41% the post-test probabilities (with 95% CI) associated with positive and negative EUS test results were 0.96 (95% CI 0.92 to 0.98) and 0.03 (95% CI 0.02 to 0.06). At the same pre-test probability, the post-test probabilities associated with positive and negative MRCP test results were 0.94 (95% CI 0.87 to 0.97) and 0.05 (95% CI 0.03 to 0.09).

Conclusion: Both EUS and MRCP have high diagnostic accuracy for detection of common bile duct stones. The two tests are similar in terms of diagnostic accuracy and the choice of which test to use will be informed by availability and contra-indications to each test.Further studies that are of high methodological quality are necessary to determine the diagnostic accuracy of EUS and MRCP for the diagnosis of common bile duct stones.

Disclosure of Interest: None declared

P0060 CLINICAL APPLICABILITY OF TOKYO GUIDELINES 2013 IN DIAGNOSIS APPROACH AND SEVERITY EVALUATION OF ACUTE CHOLANGITIS

E. Gravito-Soares¹, M. Gravito-Soares¹, D. Gomes¹, N. Almeida¹, S. Mendes¹, E. Camacho¹, R. Mesquita¹, C. Lérias¹, C. Sofia¹

¹Gastroenterology, Centro Hospitalar e Universitário Coimbra, Coimbra, Portugal

Contact E-mail Address: es18497@gmail.com

Introduction: Acute cholangitis may be associated with high morbidity and mortality. The Tokyo guidelines (TG) allowed diagnosis improvement and severity assessment of acute cholangitis and cholecystitis. However the accuracy/applicability of the updated TG 2013 remains unclear.

Objective: Diagnostic accuracy of TG13, predictors of poor prognosis in acute cholangitis and relationship with TG.

Aims & Methods: Retrospective case-control study of all episodes of obstructive jaundice, admitted to the gastroenterology service in a year, divided into two groups: those with acute cholangitis (G1: 183cases) and without acute cholangitis (G2), randomly selected in a ratio of 1:1. Variables evaluated were the clinic, analytical parameters, presence of Charcot's triad, TG07 and TG13. The prognosis was defined in terms of mortality, need of hospitalization in the intensive care unit or early ERCP (<48hours).

Results: Patients with acute cholangitis were predominantly women (58.5% vs 41.5%), with mean age 76.1 ± 11.3 years. Charcot's triad was present in 35.5%. The sensitivity/specificity for the diagnosis of acute cholangitis based on Charcot's triad, TG07 and TG13 were respectively 35.5%/100.0%, 96.2%/77.6% and 100.0%/84.7%; giving a diagnostic accuracy (p < 0.001) of 67.8%, 86.9% and 92.3%, respectively.

In relation to severity based on the TG, 30.6% of cases were severe. A worse prognosis was found in 26.8% of patients. After multivariate analysis, systolic blood pressure <90mmHg (OR 11.010[1.473;9.899]; p=0.006), serum albumin <3g/dL (OR 1.355[1.098;1.613]; p=0.006), active oncologic disease (OR 3.818[1.473;9.899]; p=0.006) and malignant etiology of obstructive jaundice (OR 3.224[1.197;8.685]; p=0.021) represented independent predictors of poor prognosis. The discriminative ability of the model with these 4 variables was high (AUROC 0.799; p < 0.001). The severity defined by the TG showed sensitivity/specificity of 65.3%/82.1%, with an accuracy of 77.6%, being explained by the 4 factors model in 80.0% (p < 0.001).

Conclusion: The TG13 showed high diagnostic accuracy in acute cholangitis, being higher than the Charcot's triad and TG07. Comparing to the TG, the simplified model allows select the patients that will benefit of admission in the intensive care unit and early ERCP.

Disclosure of Interest: None declared

P0061 CLINICAL IMPACT OF PERIAMPULLARY DIVERTICULUM AS RISK FACTOR OF THE POST-ERCP PANCREATITIS

E. J. Kim¹, J. H. Yoon¹, H. S. Kim¹, C. S. Bang¹

¹Gastroenterology, Hallym University Medical Center, Chuncheon-si, Republic of Korea

Contact E-mail Address: pure0826@hanmail.net

Introduction: Endoscopic retrograde cholangiopancreatography (ERCP) is now the therapeutic modality for biliary as well as pancreatic diseases. The correlation between Post-ERCP pancreatitis (PEP) and periampullary diverticulum (PAD) was evaluated in several studies. However, the risk of Post-ERCP pancreatitis, according to the types of PAD was not elucidated. The aim of this study was to investigate risk factors for post-ERCP pancreatitis, including three types of PAD.

Aims & Methods: We evaluated risk factors for post-ERCP pancreatitis, according to types of periampullary diverticulum. This is a retrospective case-control study, which included a total of 306 ERCPs, performed by four endoscopists in a single center. 142 (50.2%) patients with PEP, and 141 (49.8%) patients without PEP were enrolled. The correlation between PEP and risk factors, including PD, angle of common bile duct (CBD), endoscopic sphincterotomy (EST), canulation time, procedure time, and three types of PAD were investigated by univariate and multivariate analyses. PAD were classified into three types by the location of ampulla of Vater: type 1 (n= 6), inside the diverticulum; type 2 (n= 79), on the margin of diverticulum; type 3 (n= 44), outside the diverticulum.

Results: In univariate analysis, all types of PAD, type 1 PAD, type 2 PAD, type 3 PAD had variable results for PEP (Odd ratio= 1.654, 0.709, 2.815, 0.359; p= 0.036, 0.732, 0.005, 0.007, respectively). Cannulation time and total procedure time were significantly related with PEP (p= 0.004, and 0.009, respectively). However, the angle of CBD, and EST were not meaning risk factors in this study (p= 0.373, and 0.405, respectively). Age-sex adjusted multivariate analysis showed only cannulation time as independent risk factors for (OR= 1.043, p=0.01)

Conclusion: PAD, especially Type 2 PAD, cannulation time and procedure time were risk factor for PEP in univariate analysis. However, only cannulation time was significant related to PEP in multivariate analysis. Although, this study had limitations of retrospective case-control study, prospective randomized control study in multi-center was required.

Disclosure of Interest: None declared

P0062 RECURRENCE OF BILE DUCT STONES AFTER ENDOSCOPIC PAPILLARY LARGE BALLOON DILATION COMBINED WITH SPHINCTEROTOMY: LONG-TERM FOLLOW-UP. A PROSPECTIVE STUDY

G. Paspatis¹, E. Vardas¹, E. Voudoukis¹, A. Theodoropoulou¹, A. Tavernaraki¹, M. Fragaki¹, G. Chlouverakis², K. D. Paraskeva³

¹Gastroenterology, Benizelion General Hospital, ²Social Medicine, University of Crete, Heraklion, ³Gastroenterology, Konstantinoopoulion Hospital, Athens, Greece

Contact E-mail Address: gpaspatis@gmail.com

Introduction: Endoscopic papillary large balloon dilation (EPLBD) with endoscopic sphicterotomy (ES) is safe and effective in patients with large bile duct stones. Data regarding the recurrence rate of common bile duct (CBD) stones after EPLBD with ES are limited and the existing studies are retrospective.

Aims & Methods: The aim of this study was to prospectively estimate the recurrence rate and the risk factors for CBD stones after EPLBD + ES. To the best of our knowledge this is the first prospective study on this issue. In total, 106 patients who underwent EPLBD + ES from 2009 to 2011 and had successful clearance of the CBD were prospectively monitored for a minimum of three years for recurrence of CBD stones. These patients belong to a group enrolled in a randomized controlled trial and their data regarding the EPLBD + ES procedure have previously been published [1]. The follow-up was performed with regular appointments in the outpatient clinics. In those patients who became symptomatic during the follow-up period and the presence of a CBD stone was radiologically confirmed, an ERCP was performed.

Results: Of the 106 patients, the duration of follow-up was 30.5 ± 5.5 months. The recurrence rate of CBD stones was 7.5% (8/106). The mean diameter of CBD was higher for the patients with stone recurrence than for those without (2.0 ± 4.9 vs 1.65 ± 0.9, p=0.008). A multivariate stepwise logistic regression analysis revealed that the size of CBD diameter was significantly associated with the recurrence of CBD stones (odds ratio:1.2, p=0.01). Among the others evaluated parameters (sex, stone diameter, CBD tapering, cholocystectomy) no significant differences were detected as far as the stone recurrence is concerned.

Conclusion: These data show that the recurrence rate of CBD stones after EPLBD + ES is low, and a dilated CBD appears to increase the risk of bile duct stone recurrence.

Disclosure of Interest: None declared

P0063 SAFETY OF LONG-TERM BILIARY STENTING FOR COMMON BILE DUCT STONES

H. Tsugeno¹, D. Kawai¹, K. Takemoto¹, R. Takenaka¹, A. Taira¹, S. Fujiki¹

¹Digestive Endoscopy Center, Tsuyama Chuo Hospital, Tsuyama, Japan

Contact E-mail Address: attractively21@yahoo.co.jp

Introduction: Though long-term biliary stenting is a useful alternative to endoscopic extraction for common bile duct stone (CBDS) in the elderly and/or frail patients with poor tolerance for prolonged endoscopic and/or surgical procedures, the safety of long-term stenting has remained uncertain. Few reports with sufficient observation period and sample size are available on this method so far.

Aims & Methods: The immediate and long-term outcome of endoscopic biliary stenting as sole treatment of CBDS was therefore compared with the result of biliary sphincterotomy (EST) and endoscopic extraction, along with a survey on complications by cholangitis. In the past 12 years, 1195 patients with CBDS in our hospital were referred to endoscopic treatment. Among these, 401 with high risk were subjected to permanent biliary stent insertion for common duct stones and stent exchange only on complications. In 105 of 401 patients, EST had been used prior to stenting. The remaining 794 patients were subjected to endoscopic stone removal after EST. Kaplan-Meier estimates of survival and time to recurrence of cholangitis were conducted on clinical variables using the Cox model for multivariate analysis.

Results: Successful biliary drainage was achieved in all patients regardless of stone removal. The mean treatment time was significantly shorter in stent patients (21.2 min) than EST patients (41.0 min) (p < 0.01). Early complications occurred in 2.7% of stent patients and 6.1% of EST patients. Most of them were trivial except for a few with serious pancreatitis and duodenal perforation requiring surgery in EST patients. The mean hospital stay after treatment was significantly shorter in stent patients (5.3 days) than EST patients (9.3 days) (p < 0.01), and than EST patients with stone removal at once (7.9 days) (p < 0.01). Late complication of cholangitis occurred more frequently in stent patients (59.7%) than in EST patients (18.8%) within five-year observation (p < 0.01, log-rank test). The mean duration to clinical presentation of cholangitis after treatment was 3.4 years (Median: 2.7 years) in stent patients and 8.1 years in EST patients. All patient in need tolerated re-treatment adequately, without biliary tract-related mortality. In stent patients, only the size of stones was significantly correlated with occurrence of cholangitis (p < 0.05), but addition of EST was ineffective to prevent recurrence.

Conclusion: This study confirmed the usefulness and safety of long-term biliary stenting as an alternative to endoscopic common duct stone removal and in shortening the hospital stay in CBDS patients. Although recurrence of cholangitis is frequent, this method can be repeated safely, providing a feasible option for selected patients, such as the elderly and or debilitated patients with short life expectancy. Additional EST to biliary stenting failed to prevent late occurrence of cholangitis.

Disclosure of Interest: None declared

P0064 COULD IT BE POSSIBLE TO PREDICT THE RISK OF RECURRENT RESIDUAL SYMPTOMATIC CHOLEDOCHOLITHIASIS AFTER CHOLECYSTECTOMY?

M. Gravito-Soares¹, E. Gravito-Soares¹, D. Gomes¹, N. Almeida¹, S. Mendes¹, E. Camacho¹, R. Mesquita¹, S. Lopes¹, C. Sofia¹

¹Gastroenterology, Centro Hospitalar e Universitário Coimbra, Coimbra, Portugal

Contact E-mail Address: ms18498@gmail.com

Introduction: Usually, lithiasis of common biliary duct (CBD) results of the migration of sludge/gallstones from the gallbladder. Cholecystectomy would be useful in relapse prevention. However, the recurrence after cholecystectomy is observed in a considerable number of patients.

Objective: Prevalence and risk factors of recurrent residual symptomatic choledocholithiasis after cholecystectomy (RRSCC).

Aims & Methods: Of total of 1084 inpatient episodes for biliary pathology between 2011-2014, we selected 160 patients with choledocholithiasis after cholecystectomy, after exclusion of episodes with earlier recurrence, before 6 months after cholecistectomy. They were divided into 2 groups: >1 RRSCC episode (cases) versus patients with only one RRSCC (controls). All the cases had done biliary endoscopic drainage. We evaluated clinical variables, comorbidities, biochemical analysis, ultrasound and endoscopic retrograde cholangiopancreatography (ERCP) abnormalities and surgical specimens. The presence of duodenal diverticulum was based on Boix et al. classification.

Results: RRSCC occurred in 26.9% of patients (n=43). The efficacy of ERCP was 76.3% with a mean number of 1.4 ± 0.7(vs 1.2 ± 0.5; p=0.109) exams. It was technically impossible in 4.4% of cases and the complications peri/post- procedure, mainly pancreatitis, was 13.1%, without any case of mortality. Of cases, the mean time of cholecistectomy-recurrence was 8.5 ± 11.2 years, the mean number of relapses was 3.6 ± 2.2 with mean inter-relapses of 11.5 ± 14.1 months, mean number of choledocholithiasis episodes before cholecistectomy of 1.6 ± 1.2(vs 1.3 ± 0.7; p=0.017) and necessity of surgical treatment in 7.0%. The duodenal diverticulum was presented in 32.6% (vs 9.4%; p=0.001), periampullary(<2cm of papilla) in 27.9%(vs 12.0%; p=0.005) and intradiverticular papilla in 16.3%(vs 4.3%; p=0.017). After multivariate analysis, independent risk factors for relapse of RRSCC were American Society of Gastrointestinal Endoscopy (ASGE) criteria at admission ≥2 (2.8 ± 0.5 vs 2.4 ± 0.6; OR1.554 ,p=0.030; AUROC0.624, p=0.017), CBD ultrasound dilatation ≥12mm at admission (16.5 ± 5.2 vs 13.1 ± 4.5; OR1.145, p=0.002; AUROC0.702, p < 0.001) and the presence of periampullary diverticulum (27.9% vs 12.0%; OR3.115, p=0.003).

Conclusion: After a first episode of RRSCC, approximately ¼ of patients will relapse after about 9 years. Patients with ASGE criteria ≥2 at admission, biliary ultrasound dilatation ≥12mm at admission or periampullary diverticulum, will require a careful follow-up and eventually surgical treatment.

Disclosure of Interest: None declared

P0065 THE ECTOPIC OPENING OF COMMON BILE DUCT INTO THE DUODENAL BULB AND GASTRIC ANTRUM AND ITS CLINICAL IMPORTANCE

M. Kaya¹, N. Ekin¹, R. Bestas², F. Ucmak¹

¹Gastroenterology, Dicle University School of Medicine, ²Gastroenterology, Diyarbakır Gazi Yasargil Education and Training Hospital, Diyarbakır, Turkey

Contact E-mail Address: bestasr@gmail.com

Introduction: Ectopic of the common bile duct (CBD) into the duodenal bulb and gastric antrum is an extremely rare congenital anomaly, but its clinical significance has not been adequately determined.

Aims & Methods: The aim of this study was to comprehensively describe the features of this rare anomaly. Clinical, laboratory, endoscopic and cholangiographic findings, therapeutic interventions, and clinical course of consecutive patients that underwent endoscopic retrograde cholangiopancreatography (ERCP) and were diagnosed as ectopic opening of CBD into the duodena bulb and gastric antrum.

Results: Ectopic opening of the CBD was observed in 10 (1.5%) (7 males and 3 females; median age: 56.3 years) of 637 patients that underwent ERCP. All but 1 of the patients with ectopic opening of the CBD had a history of recurrent episodes of cholangitis, and 1 had compensated cirrhosis. The ectopic opening was into the antrum in 2 patients and into the duodenal bulb in 8 patients. In all, 6 of the patients had an ulcer (duodenal: n = 4; gastric: n = 2) and 7 had duodenal deformity associated with apical stenosis. Cholangiography showed dilatation of both the extrahepatic and intrahepatic bile ducts, and tapered narrowing and a hook-shaped configuration of the distal end of the CBD in all 10 patients, bile stones in 7 patients, and bile sludge in 3 patients. Complete clearance of the bile ducts was achieved in all patients with bile sludge and in 1 of the 7 patients with bile stones following balloon dilation of the orifice.

Conclusion: Ectopic opening of the CBD into the duodenal bulb and gastric antrum is usually associated with gastroduodenal and biliary disease. ERCPists should be aware of this anomaly. Abnormal configuration of the biliary tree prevents complete extraction of bile stones in most patients.

Disclosure of Interest: None declared

P0066 PREVALENCE AND RISK FACTORS OF GALLBLADDER STONE IN KOREAN HEALTH EXAMINEE

T. N. Kim¹, S. B. Kim¹, S. H. Sohn¹, Y. H. Jeong¹, K. H. Kim¹, K. O. Kim¹, S. H. Lee¹, B. I. Jang¹

¹Gastroenterology and Hepatology, Yeungnam University Hospital, Daegu, Republic of Korea

Contact E-mail Address: tnkim@yu.ac.kr

Introduction: Female gender, age, diabetes mellitus, rapid weight loss, use of oral contraceptives, pregnancy, menopause, chronic hepatitis C, chronic kidney disease and metabolic syndrome have been known as the risk factors of gallbladder (GB) stones. In western countries, females showed higher prevalence of gallbladder (GB) stone than males. However, prevalence of GB stone was higher in males than females in some studies.

Aims & Methods: The aims of this study were to evaluate the prevalence and risk factors of GB stone. Patients who underwent examination through health promotion center in Yeungnam university hospital from Jan 2010 to Dec 2013 were analyzed retrospectively. All subjects checked height, weight, abdominal circumference, and blood pressure and underwent laboratory tests and abdominal ultrasonography. Diagnosis of GB stone was made by abdominal ultrasonography. Subjects with history of cholecystectomy or without visible GB were excluded from this study.

Results: Of the total 23,899 subjects (mean age, 50.0 ± 11.4 years, male to female ratio, 1.3:1), GB stone was diagnosed in 1,259 subjects with overall prevalence of 5.2%. Mean age of the patients with GB stone was 55.4 ± 11.3 years and male to female ratio was 1.6:1. Prevalence of GB stone was significantly higher in male than female (5.7% vs 4.4%, p < 0.001). Males had higher prevalence of GB stone than females in all age groups. Metabolic syndrome (MS) was more frequent in male subjects than females (18.6% vs 13.9%, p < 0.01). Subjects with MS had higher incidence of GB stone compared to subjects without MS (23.3% vs 16.2%, p < 0.001). Males had higher prevalence of MS than females in the age below 60 (22.4% vs 15.5%, p=0.016). However, the prevalence of MS was higher in females than in males in age above 60 (41.6% vs 23.0%, p=<0.001). On multivariate analysis, older age (95% CI, 1.035-1.046; p < 0.001), male gender (95% CI, 1.171-1.496; p < 0.001), high blood pressure (95% CI, 1.491-1.876; p < 0.001), low HDL cholesterol level (95% CI, 1.106-1.436; p=0.001), abdominal obesity (95% CI, 1.082-1.408, p=0.003) and chronic hepatitis B (95% CI, 1.008-1.684; p=0.036) were found as risk factors of GB stone.

Conclusion: The prevalence of GB stone was 5.7% in males and 4.4% in females with overall prevalence of 5.2%. Age, male gender, high blood pressure, low HDL cholesterol, abdominal obesity and chronic hepatitis B were found as risk factors of GB stone.

Disclosure of Interest: None declared

P0067 THE MANAGEMENT OF BILE DUCT STONES IN VERY ELDERLY PEOPLE

T. Suzuki¹, O. Togawa¹, T. Watanabe¹, H. Kogure¹, Y. Osawa¹, H. Oyama¹, E. Goto¹, Y. Isomura¹, M. Seto¹, Y. Koike¹

¹Gastroenterology, Kanto Central Hospital, Setagaya-Ku, Japan

Contact E-mail Address: suzutatsu86@gmail.com

Introduction: Life expectancy has been prolonged all over the world, particularly in Japan. The increasing population of very elderly people raises the prevalence of bile duct stones. Very elderly patients often have concomitant heart or cerebrovascular diseases. We evaluated the safety of the endoscopic treatment for bile duct stones.

Aims & Methods: From April 2010 to March 2015, 289 consecutive patients (58.5% men; mean age, 75 years) with bile duct stones who underwent endoscopic retrograde cholangiopancreatography (ERCP) were included in the present study. Patients were divided into two age groups: group A (≧85 years old) (n=76) and group B (<85 years old) (n=213). We performed endoscopic papillary balloon dilation (n=242), endoscopic papillary large balloon dilation (n=25), endoscopic sphincterotomy (n=22) to remove bile duct stones.

Results: Patients in group A had larger (8.3mm vs 6.8mm, p=0.031) and more (3.4 vs 2.3, p=0.004) stones than in group B with significant differences. Overall, bile duct clearance rates were similar in the two groups (96.1% vs 98.6%, p=0.188), and the mean number of sessions required for complete stone removal was similar in the two groups (1.3 vs 1.2, p=0.395). The incidence of post-ERCP pancreatitis was lower in group A than in group B (3.9% vs 11.3%, p=0.067) but was not statistically different. The incidence of pneumonia was higher in group A than in group B (2.6% vs 0%, p=0.069) but was not statistically different. Duration of hospitalization was significantly longer in group A than in group B (20.0 vs 12.9, p < 0.001).

Conclusion: Although very elderly patients had larger and more stones, bile duct clearance rate was similar. ERCP is safe technique for the treatment of bile duct stones in very elderly patients as well, without increased occurrence of pancreatitis.

Disclosure of Interest: None declared

P0068 THE EFFICACY OF RECOMBINANT HUMAN SOLUBLE THROMBOMODULIN IN PATIENTS WITH BILIARY TRACT INFECTION-INDUCED DISSEMINATED INTRAVASCULAR COAGULATION

T. Ito¹, A. Nagahara¹, J. Kato¹, H. Ueyama¹, H. Saito¹, R. Kanazawa¹, R. Shimizu¹, K. Tomishima¹, S. Ishii¹, J. Sai¹, S. Shiina¹, S. Watanabe¹

¹gastroenterology, Juntendo University, Tokyo, Japan

Contact E-mail Address: tmitou@juntendo.ac.jp

Introduction: The biliary tract infectious disease is sometimes serious, sometimes resulting in disseminated intravascular coagulation (DIC). Recently, recombinant human soluble thrombomodulin (rTM) was approved and has been used in clinical practice for DIC treatment in Japan. However, there are few studies to evaluate the efficacy of rTM for DIC with the biliary tract infection. The purpose of this study is to make a comparison between rTM-treated patients and patients treated other agents, and to evaluate the efficacy of rTM.

Aims & Methods: Thirty-nine inpatients at our department with biliary tract infection-induced DIC between January 2009 and March 2015 were retrospectively analyzed. The patients were classified into the rTM treatment group (n=20), and conventional treatment group (rTM was not used) as the control group (n=19). Diagnosis of DIC was made according to the criteria of acute DIC of the Japan Association of Acute Medicine (JAAM). Platelet count, prothrombin time-international normalized ratio (PT-INR), levels of fibrin/fibrinogen degradation products (FDP), C-reactive protein (CRP), DIC scores based on JAAM criteria were measured on days 0.3, and 7 to evaluate therapeutic results. Furthermore, DIC resolution rate were assessed 3 and 7 days after the start of DIC treatment.

Results: There were no significant differences between two groups regarding patient characteristics. All patients underwent biliary drainage. The duration of rTM administration was 3.6 ± 1.7 days (range 1 to 8 days). As shown in the table, significant intra-group improvement was observed in all parameters except for FDP in both groups. However, there were no significant inter-group differences in comparison of all parameters except DIC scores. Significant improvements were seen in the DIC scores in the rTM-treated group (p < 0.05). DIC resolution rate on day3 were higher in the rTM group than in the control group (65% vs 32% on day3, p < 0.05).

Abstract Number: P0068

		Day0	Day3	Day7
Platelet count(104/µL)	rTM control	9.9 ± 5.7 12.1 ± 6.9	11.9 ± 5.6 10.2 ± 5.6	18.6 ± 9.1** 18.2 ± 7.8**
PT-INR	rTM control	1.47 ±0.35 1.41 ± 0.27	1.24 ± 0.20* 1.15 ± 0.25*	1.27 ± 0.26* 1.17 ± 0.18*
FDP (µg/ml)	rTM control	25.1 ± 17.1 39.7 ±36 .4	20.1 ± 25.6 21.5 ± 11.0	18.0 ± 14.9 18.2 ± 9.5
CRP (mg/dL)	rTM control	13.5 ± 7.1 16.2 ± 7.9	9.9 ± 5.8* 12.2 ± 6.3*	5.7 ± 4.8** 7.3 ± 4.6**
DIC score	rTM control	5.2 ± 1.2 5.7 ± 1.1	2.8 ± 1.6** 3.8 ± 1.7**$	1.8 ± 1.4** 2.1 ± 1.5**$
DIC resolution rate (%)	rTM control		65$32	8078

Data are shown with Mean ± SD *p < 0.05 vs. Day0, **p < 0.01 vs. Day0$p < 0.05 rTM vs control

Conclusion: These results suggest that rTM would be the useful medicine for early improvement of biliary tract infection-induced DIC.

Disclosure of Interest: None declared

P0069 LASER LITHOTRIPSY FOR GIANT STONES OF BILE DUCT UNDER PERORAL DIRECT CHOLANGIOSCOPY THROUGH TRACTION OF THE BENDING PART OF ULTRASLIM GASTROSCOPE

Y.-H. Huang¹, H. Chang¹, Y. Wang¹, W. Yao¹, Y.-P. Zhang¹

¹Peking University Third Hospital, Beijing, China

Contact E-mail Address: pksunking@live.cn

Introduction: To evaluate the feasibility and usefulness of a new peroral direct cholangioscopy(PDSC) technique through traction of the bending part of ultraslim gastroscope for the laser lithotripsy of giant stones of bile duct.

Aims & Methods: This study involved 9 patients with giant stones of bile duct whose endoscopic treatment failed by a conventional method involving mechanical lithotripsy. Firstly, endoscopic retrograde cholangiography (ERC) and small sphincterotomy was performed using a conventional duodenoscope. Endoscopic papillary balloon dilation was performed up to 12-15mm before the introduction of an ultraslim upper endoscope(Fijinon 530NW). Before inserting the ultraslim gastroscope, a snare was tightened around the end of the bending section of the scope(about 6cm from the tip). Then the ultraslim gastroscope was advanced into the duodenum with the snare. A J turn was made in the second portion of the duodenum, and the tip of the endoscope was positioned facing the papilla. Then the snare was pulled slightly as a fulcrum to prevent the endoscope be pushed too far downward in the duodenum and to make insertion of the endoscope easier. Using this method, the ultraslim gastroscope was advanced into the CBD, and laser lithotripsy (U100plus, Germany) was performed. The stone fragments were extracted by basket and balloon through PDSC or ERC finally.

Results: The procedures of PDSC and laser lithotripsy were succeeded in all 9 patients (5 men and 4 women; mean age 79.7 years, range 52-93 years). The mean diameter of giant CBD stones was 23.2mm (range, 14-40mm). The overall success rate of bile duct clearance by laser lithotripsy and extraction was 100%. The mean intubation time was 8.8 minutes (range, 4-16 minutes). No procedure-related complications were observed.

patient	sex	age	Stone size (mm)	Intubation time (min)	No. of times entering CBD
1	M	70	14	10	1
2	F	93	20	8	1
3	M	52	25	14	4
4	M	77	40	4	6
5	M	93	20	4	2
6	F	85	20	7	2
7	F	86	22	9	2
8	F	86	30	8	3
9	M	75	18	16	1

Conclusion: Snare-assisted PDSC through traction of the bending part of ultraslim gastroscope and laser lithotripsy were safe, simple and practical techniques for the treatment of giant stones of bile duct. The new PDSC method sometimes facilitated the entrance into bile duct repeatedly for further procedures including direct removal of stone fragments.

Disclosure of Interest: None declared

P0070 FEASIBILITY OF ENDOSCOPIC PAPILLARY LARGE BALLOON DILATION IN PATIENTS WITH DIFFICULT BILE DUCT STONES AND WITHOUT DILATATION OF THE LOWER PART OF THE EXTRA-HEPATIC BILE DUCT

Y. Fujita¹, K. Kagawa², T. Fujisawa², N. Fujisawa³, Y. Sekino¹, K. Hosono¹, N. Matsuhashi², K. Sakamaki⁴, A. Nakajima¹, K. Kubota¹

¹Gastroenterology and Hepatology, Yokohama City University School of Medicine, Kanazawa-ku Yokohama-shi, ²Gastroenterology, NTT Medical Centre Tokyo, shinagawa-ku Tokyo, ³Gastroenterology, Tokyo Metropolitan Hiroo Hospital, shibuya-ku Tokyo, ⁴Medical Statistic, Yokohama City University School of Medicine, Kanazawa-ku Yokohama-shi, Japan

Contact E-mail Address: yufuji5395@gmail.com

Introduction: Endoscopic sphincterotomy (EST) combined with mechanical lithotripsy (ML) is an established method for the removal of difficult biliary stones. Some bile duct stones were difficult to remove because of their large size, the rectangular shape of the CBD, or anatomical difficulties interfering with endoscopic procedures. Ersoz et al. first reported on the usefulness of large balloon (10–20 mm in diameter) dilation after EST (EPLBD) for the removal of large bile duct stones in 2003¹. However, difficult cases have been encountered with large stones and without dilatation of the lower part of the CBD (WDLBD). The usage of the combination of EST and ML in such cases often requires multiple treatment procedures, whereas EPLBD has been avoided so far because of the high risk of procedure-associated complications.

Aims & Methods

Aims: To evaluate the technical feasibility and safety of EPLBD for the removal of large bile duct stones in WDLBD patients.

Methods: Between October 2009 and July 2014, 212 patients underwent EPLBD for the removal of bile duct stones at Yokohama City University Hospital, NTT Tokyo Medical Center, and Tokyo Metropolitan Hiroo Hospital. We retrospectively reviewed them. There were 60 patients (28.3%) in the WDLBD group and 152 patients (71.7%) in the non-WDLBD group. The state WDLBD was defined as a state with the diameter of the lower part of the extra-hepatic bile duct <10 mm and its length >10 mm as measured by cholangiography.

Results: There were no significant differences between the two groups in the total success rates (100% vs. 98.7%), frequencies of the use of mechanical lithotripter (31.7% vs. 23.0%, P = 0.193), and recurrence rates (3.3% vs. 4.6%). The success rate in the first session was significantly lower (63.3% vs. 75.7%, P = 0.040) and the procedure time was significantly higher (58.1 ± 31.5 vs. 48.1 ± 22.9, P = 0.032) in the non-WDLBD group. There were no significant differences in the rates of post-ERCP pancreatitis, perforation, and bleeding (6.7% vs. 3.3%, P = 0.471, 0% vs. 1.3%, P = 0.917, and 1.7% vs. 0.7%, P = 0.917, respectively).

Conclusion: EPLBD appears to be a safe and effective method for the common bile duct stone removal in WDLBD patients.

Disclosure of Interest: None declared

P0071 COST-EFFECTIVENESS TRIAL OF SELF-EXPANDABLE METAL STENTS AND PLASTIC BILIARY STENTS IN MALIGNANT BILIARY OBSTRUCTION

A. Fábián¹, R. Bor¹, T. Daróczi¹, K. Farkas¹, A. Bálint¹, F. Nagy¹, Á. Milassin¹, M. Rutka¹, M. Szűcs², T. Molnar¹, Z. Szepes¹

¹University of Szeged, First Department of Medicine, ²Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary

Contact E-mail Address: szepes.zoltan@med.u-szeged.hu

Introduction: Self-expandable metal (SEMS) and plastic stents can be applied in the palliative endoscopic treatment for patients with unresectable malignant biliary obstruction. SEMS is substantially expensive, but the stent patency is significantly longer. Current guidelines recommend the use of SEMS if the patient's life expectancy is more than four months.

Aims & Methods: The aims of this study were to compare the therapeutic efficacy and cost-effectiveness of SEMS and plastic stents in the treatment of malignant biliary obstruction. 74 patients with unresectable malignant biliary obstruction were retrospectively enrolled who received a SEMS (34 patients) or a plastic stent (34 patients). We evaluated the technical and functional success, the complication rate, the stent patency and the cumulative cost of treatment.

Results: The complication rate of SEMS was lower compared with plastic stents (40.54% vs. 56.76). The stent occlusion was the most frequent complication. The mean time of stent patency were significantly higher in the SEMS group (19.11 vs. 8.29 weeks; p=0.0041). In these cases the length (10.89 vs. 13.7 days; p=0.19) and frequency (1.18 vs. 2.32; p=0.05) of hospitalization of patients in context with stent complications were substantially lower, but the necessity of reintervention for stent dysfunction was higher (17 vs. 27; p=0.033). In the plastic stent group the multiple stent implantation increased the stent patency: the second stent raised it from 7.68 to 10.75 weeks. In the three quarter of cases the stent complications were manageable endoscopically in both groups: re-ERCP, re-stent implantation or stent replacement were performed. There was no difference in the total cost of treatment of malignant biliary obstruction between the two groups (p=0.848). If the patients’ survival time was more than two months, the cost-effectiveness of SEMS was better than plastic stents.

Conclusion: Considering the cost of treatment, the burden of patients and health care system we recommend the SEMS implantation if the life expectancy of patients is more than two months. In short survival cases or if the SEMS not available the multiple plastic stent implantation is recommended.

Disclosure of Interest: None declared

P0072 GALLBLADDER CARCINOMA: THE 6 YEARS EXPERIENCE OF A TERTIARY REFERRAL CENTER

A. Peixoto¹, M. Silva¹, P. Pereira¹, G. Macedo¹

¹Gastroenterology, Centro Hospitalar de São João, Porto, Portugal

Contact E-mail Address: armandoafp5@gmail.com

Introduction: The gallbladder carcinoma is an uncommon neoplasm but often fatal, with a high geographical variability in relation to its incidence.

Aims & Methods: The authors propose to evaluate the clinical and pathological aspects of this neoplasm and its relation with cholelithiasis, as well as its prognosis. Retrospective analysis of patients with diagnosis of gallbladder cancer between 2008-2013, in a referral tertiary center.

Results: We included 44 patients (68% women), with a median age of 70 years. The median time of follow-up was 6 months, with a mortality rate of 71% (n= 31). The majority of patients (61%) had history of cholelithiasis and 46% were diagnosed after cholecystectomy (35% of these in the context of acute cholecystitis). The most common symptoms reported at admission were abdominal pain (59%), jaundice (41%), and nausea/vomiting (34%). The majority of the patients had slight cholestasis in laboratorial analysis. The neoplasms involved the gallbladder body or were panvesicular in 77% of cases. A non-specific adenocarcinoma was the most common diagnosis (86%), with a median size of 33mm. At diagnosis, 84% were in an advanced stage (III/IV). A surgery of curative intent was performed in 59% of patients. The palliative approaches more frequently used were percutaneous drainage (39%) and chemorradiotherapy (27%). An endoscopic drainage was performed only in 6 patients (14%). The mortality rate at 3, 6, 12 and 24 months was 23%, 39%, 55% and 66%, respectively. The presence of cholestasis (p=0.036) and renal dysfunction (p=0.012) at diagnosis correlated independently with early mortality.

Conclusion: The gallbladder carcinoma was more prevalent in women with advanced age, in many cases with prior cholelithiasis and in an advanced stage at diagnosis. Adenocarcinoma was the most common histological type. Despite the high rate of surgical approaches for curative intent, 66% did not survive beyond 2 years after the diagnosis.

Disclosure of Interest: None declared

P0073 DIRECT RETROGRADE CHOLANGIOSCOPY-DIRECTED BIOPSY IS SUPERIOR TO FLUOROSCOPY-GUIDED BIOPSY TO DIFFERENTIATE INDETERMINATE BILIARY STRICTURE IN THE DISTAL COMMON BILE DUCT, BUT NOT IN THE PORTA HEPATIS

D. Walter¹, M. Friedrich-Rust¹, S. Zeuzem¹, J. Albert¹

¹Medical Department 1, University hospital Frankfurt, Frankfurt, Germany

Contact E-mail Address: dirk.walter@kgu.de

Introduction: Differentiation of indeterminate biliary stricture (IBS) by imaging modalities is limited. Definite diagnosis is based on histopathology, but high rates of false negative biopsies constrain the clinical management.

Aims & Methods

Aims: To investigate reason of high false negative results of intraductal biopsies obtained under fluoroscopic guidance in comparison to direct retrograde cholangioscopy (DRC).

Methods: All patients were retrospectively included who presented for diagnostic workup of IBS at our University hospital and who underwent an intraductal biopsy between 2009 and 2015. Histopathological results of fluoroscopic vs DRC-directed intraductal biopsies were compared with the golden standard of either postoperative histology or follow-up of at least one year and underlying disease of false negative biopsies in proximal and distal biopsies was compared.

Results: 106 patients were included in this study. IBS was evaluated by fluoroscopy-guided biopsy in 68 patients and by DRC-directed biopsy in 38 patients. A malignant stenosis was diagnosed in 47/106 cases (44.3%). Sensitivity and specificity for fluoroscopy guided and DRC directed biopsies were 46% and 100% vs. 58% and 100%, respectively. Underlying disease in the 24 false negative histological diagnoses was cholangiocarcinoma (CCA, 14/24, 58%), adenocarcinoma of the pancreatic head (PC, 7/24, 29%) and others (3/24, 13%). Majority of false negative samples was in distal biopsies (19/24, 79%), where etiology was mainly CCA (9/20, 45%) and PC (7/20, 37%). Etiology in false negative biopsies in the hilar region was only CCA (n=5, 100%). DRC directed biopsy correctly detected all PC (2/2, 100%) compared to 2/9 PC (22%) found by fluoroscopy guided biopsy and 4/8 CCA (50%) compared to 6/16 CCA (37.5%), respectively.

Conclusion: DRC is superior to fluoroscopy in distinguishing ductal infiltration from external common bile duct compression, e.g. in PC, and might be preferred to direct intraductal biopsies.

Disclosure of Interest: None declared

P0074 ENDOSONOGRAPHY-GUIDED BILIARY DRAINAGE: EXPERIENCE COUNTS

H. Sentürk¹, O. Masri², B. Baysal³, M. Basaranoglu³

¹Bezmialem University, Istanbul, Turkey, ²Lebanon Medical Centre, Lebanon, Lebanon, ³Bezmialem Uniiversity, Istanbul, Turkey

Contact E-mail Address: drhakansenturk@yahoo.com

Introduction: ERCP is unsuccessful in 10% of the cases of biliary obstruction. Previously, percutaneous transhepatic drainage was the only alternative. Recently, endosonography (EUS) –guided drainage was suggested as an alternative. However, the technique is still in evolution

Aims & Methods

Aim: To assess the efficacy and safety of different techniques in EUS-guided biliary drainage.

Patients and Methods: We collected the data of 59 patients treated over 46 months. The data included baseline characteristics, indications, techniques, success rates and complications. Patients were classified according to the different types of approaches shown in Table. In the first 41 months, we used tapered ERCP catheter, and in case it fails, needle-knife sphincterotomy for inital tract dilation and plastic or metal stents eventually. For the last five months, we revised our technique so that we used exclusively 6F cystotome. We preferred CDS over HGS in distal obstructions in long-scope position.

Results: The overall results and the results after it was broken down to previous 41 months (group B) vs. the last 5 months (group A) are shown in Table 1. Work volume was 0.97 patient per month in group B vs. 3.8 in group A (p < 0.05). There was no significant difference between the groups for any indication (NS). Technical success rate in group A was significantly higher in group A (p: 0.046) and complication rate was lower (p=0.045).

Abstract number P0074 Table 1.

	Hepato-gastrostomy jejunostomy[HG(J)S]	Choledocho or cystoduodenostomy [CD(Cy)S]	Choledochal-Rendezvous (C-RV)	Cholecysto- gastrostomy- jejunostomy[CG(J)S]	Total
Number of the pts (A/B)	7/24	8/6	2/10	2/0	19/40
Male-Female	22-9	8-6	8-4	1-1	39-20
Mean age (range) years	67 (34-87)	61 (45-81)	65 (48-80)	60 (52-68)	65 (34-87)
Malignities Benign pathologies Indications (A/B)	7/2 20/2	7/4 1/2	0/4 2/6	2/0 0/0	16/30 3/10
Technical success rate A/B  (Number of the patients)#	[100% (7/7)/87.5% (21/24)]	[100% (8/8)/50% (3/6)]	[100% (2/2)/60% (6/10)]	[100% (2/2)/0/0	[100% (19/19)/77.5% (31/40)]]
Serious Complications:A/B¥	0/5 (Bleeding in two cases-one died, one surgery; cholangitis and sepsis in one case; perforation in two cases (surgery needed)	0/2 (Bile leak and biloma formation (10 cm) requiring surgery in one-cardiopulmonary arrest and death in one)	0/1 (Surgery due to guide-wire knotting in duodenum)		0/8 (2 death, 5 surgery, 1 extended intensive care stay)

Conclusion: Experience, volume of the centre and the initial tract dilation technique and use of metallic stent are the most important determinants of success and complications in EUS-guided biliary drainage.

Disclosure of Interest: None declared

P0075 SIMVASTATIN USE AND ITS IMPACT ON SURVIVAL IN PANCREATIC CANCER PATIENTS

H. S. Lee¹, H. J. Lee¹, S. H. Lee¹, M. J. Chung¹, J. Y. Park¹, S. Bang¹, S. W. Park¹, S. Y. Song¹, J. B. Chung¹

¹Division of Gastroenterology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University Health System, Seoul, Republic of Korea

Contact E-mail Address: lhs6865@gmail.com

Introduction: Statins are cholesterol-lowering medications and are associated with a number of signaling pathways involved in carcinogenesis. Recent observational studies raised the possibility that the use of statins may reduce the overall mortality in various types of cancer. We investigated whether statins used after pancreatic cancer diagnosis reduce the pancreatic cancer mortality in patients with pancreatic cancer.

Aims & Methods: We analyzed data on 2981 patients newly diagnosed with pancreatic cancer between January 1, 2006 and December 31, 2014. We used the Cox proportional hazards regression model to estimate mortality among pancreatic cancer patients according to statin use.

Results: Among the 2981 patients, 428 pancreatic cancer patients had used statins. During the study period, 1616 patients (54.2%) died. After adjustment for age, sex, tumor characteristics, DM, dyslipidemia, BMI, and tumor marker, statin use was associated with lower risk of pancreatic cancer death (HR, 0.821; 95% Confidence interval, 0.716 – 0.941), especially among simvastatin users (HR, 0.620; 95% Confidence interval, 0.448 – 0.858). Subgroup analysis showed that patients who used simvastatin in non-resectable pancreatic cancer had more favorable outcomes than patients with resectable pancreatic cancer.

Conclusion: We found that the use of statins after cancer diagnosis is associated with longer survival in patients with pancreatic cancer. This effect was stronger in patients who used simvastatin in advanced pancreatic cancer.

Disclosure of Interest: None declared

P0076 THE POSSIBILITY OF LIQUID BIOPSY WITH BILE JUICE IN PATIENTS WITH GALLBLADDER CANCER

H. Kinugasa¹², K. Matsumoto¹, K. Tsutsumi¹, H. Kato¹, K. Nouso¹³, H. Okada¹

¹Gastroenterology and hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, ²Gastroenterology and hepatology, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, ³Gastroenterology, Okayama Citizens Hospital, Okayama, Japan

Contact E-mail Address: gyacy14@gmail.com

Introduction: Gallbladder cancer (GBCa) is one of the most difficult to treat cancers in the field of gastroenterology. To achieve good treatment effect in future, so called “custom-made” therapy based on the character of the each tumor is mandatory. However, GBCa tissue cannot be obtained easily. In this study, we try to elucidate the possibility of “liquid biopsy” with bile juice on the concept of non- invasive diagnostic method as circulating tumor DNA in blood.

Aims & Methods: Eleven patients with GBCa enrolled in this study. Surgically removed tumors and their surrounding normal tissue were analyzed for mutations of 48 oncogenes (Cancer panel; Haloplex, Agilent Technology) by next generation sequencing (NGS; Illumina, San Diego, CA, USA) in all patients. Bile juice obtained from 6 of 11 patients prior to the treatment was examined simultaneously. As negative controls, additional 2 healthy gallbladder tissue samples were analyzed.

Results: We set cut-off value at 3% for rare mutation rate. TP53 mutation was detected in 2/11 (18.2%) of the tumor tissue. Mutations of CTNNB1, MET, AR were detected in 1/11 (9%), 1/11 (9%), 1/11 (9%) samples, respectively. In these mutation-positive samples, more than 10% of the DNA was mutated in 23.8% of TP53 (E153K), 15.9% of TP53 (R148K) and 29.7% of CTNNB1 (T41I). None of the corresponding normal tissues and controls had any mutations. Interestingly, we could detect the same TP53 mutation even in bile juice as liquid biopsy in patients who had TP53 mutation in tumor tissue (2/2; 100%).

Conclusion: Tumor DNA in bile juice could be detected by NGS. It may allow us to make a new genetic diagnosis of GBCa.

Disclosure of Interest: None declared

P0077 RANDOMIZED TRIAL COMPARING THE EFFICACY OF BILATERAL METALLIC STENT DEPLOYMENT WITH THAT OF UNILATERAL DEPLOYMENT IN PATIENTS WITH MALIGNANT HILAR BILIARY STRICTURES DUE TO BILIARY TRACT CARCINOMA

H. Kawamoto¹, Y. Yamashita², on behalf of Bilio-Pancreatic Stenting Study Group, H. Kato³, Y. Furukawa⁴, M. Kitano⁵, K. Kamada⁶, T. Ogawa⁷, K. Fujita⁸, Y. Okabe⁹, R. Kaji¹⁰, D. Masuda¹¹, M. Murata¹², S. Hashimoto¹³, K. Tanaka¹⁴, Y. Arisaka¹⁵, H. Mukai⁸, on behalf of Bilio-Pancreatic Stenting Study Group

¹Department of General Internal Medicine 2, Kawasaki Medical School, Okayama, ²Gastroenterology, Japanese Red Cross Society Wakayama Medical Center, Wakayama, ³Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, ⁴Gastroenterology, Hiroshima Red Cross Hospital & Atomic-Bomb Survivors Hospital, Hiroshima, ⁵Gastroenterology and Hepatology, Kinki University Faculty of Medicine, Osaka, ⁶Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, ⁷Medicine, Hiroshima City Hospital, Hiroshima, ⁸Gastroenterology, Yodogawa Christian Hospital, Osaka, ⁹Gastroenterology, Kurume University School of Medicine, Kurume, ¹⁰Gastroenterology, Tagawa Hospital, Tagawa, ¹¹Gastroenterology, Osaka Medical College, ¹²Gastroenterology, Osaka Police Hospital, Osaka, ¹³Gastroenterology, Kagoshima University Faculty of Medicine, Kagoshima, ¹⁴Gastroenterology, the Second Kyoto Red Cross Hospital, Kyoto, ¹⁵Gastroenterology, Kobe University Graduate School of Medicine, Kobe, Japan

Contact E-mail Address: hirofumi.kawamoto@gmail.com

Introduction: Several single-arm studies demonstrated the feasibility of metallic stent (MS) in the management of the malignant hilar biliary strictures (HBS). However, the efficacy of the bilateral MS deployment to the malignant HBS has not been compared and discussed with those of unilateral MS deployment yet.

Aims & Methods: We conducted the multi-center prospective randomized study to investigate the clinical significance of the bilateral MS deployment to the patients with malignant HBS caused by unresectable biliary tract carcinoma (BTC) (UMIN000005182). To exclude the possibility to include the patients who absolutely needed bilateral stenting, the patients with HBS due to pathologically confirmed unresectable BTC were subjected to the unilateral biliary decompression before MS deployment. The patients whose unilateral portal blood flow was lost due to tumor invasion were also excluded. The biliary branch to be drained first was that which drained the most part of the liver under the CT or MR imaging. After confirming the improvement of the liver function, the patients gave informed consent and were randomly allocated to the endoscopic unilateral or bilateral MS deployment. The MS which was employed in this study is Zeostent (Zeon Medical, Tokyo, Japan). The patients who were allocated to the bilateral stenting (BS) had two MS deployed in the initially inserted branch and the branch of the contralateral lobe using the endoscopic partial stent-in-stent procedure. The patients who were allocated to the unilateral stenting (US) had one MS deployed in the initially selected branch. The primary endpoint is the stent-functioning (SF) time, the definition of which is the time from the MS deployment to the stent dysfunction which necessitates the biliary interventions. The data was analyzed based on the intention-to-treat.

Results: Between April 2011 and March 2014, 86 patients with BTC were enrolled in this study. After excluding 7 patients due to patients’ refusal, death before stenting, breach of protocol or misdiagnosis, 40 patients were randomly allocated to the BS group and 39 patients to the US group. The procedure success rate was 93% (37/40) in BS group and 100% (39/39) in US group (ns). The early pancreatobiliary complication rate was 25% (10/40) in BS group and 23% (9/39) in US group (ns). The mean survival time was 237 days in BS group and 236 days in US group (ns). The mean SF time was 295 days in BS group and 187 days in US group (ns, p=0.075). The biliary re-intervention was successfully performed on both groups. Other late complications were noted in US group only.

Conclusion: Judging from these data, it is suggested that the bilateral MS deployment is the procedure to try first for the patients with HBS due to unresectable BTC.

Disclosure of Interest: None declared

P0078 PREDICTIVE FACTORS FOR POSITIVE DIAGNOSIS OF MALIGNANT BILIARY STRICTURES BY TRANSPAPILLARY BRUSH CYTOLOGY AND FORCEPS BIOPSY

H. Kondo¹, I. Naitoh¹, T. Nakazawa¹, K. Hayashi¹, K. Miyabe¹, S. Shimizu¹, Y. Nishi¹, M. Yoshida¹, S. Umemura¹, Y. Hori¹, A. Kato¹, H. Ohara², T. Joh¹

¹Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, ²Department of Community-based Medical Education, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

Contact E-mail Address: hkondo@med.nagoya-cu.ac.jp

Introduction: Endoscopic transpapillary brush cytology and forceps biopsy are used widely for the pathological diagnosis of malignant biliary strictures (MBS). However, the diagnostic yield remains unclear because of the wide variation in reported values, and predictive factors for a positive diagnosis using these methods have not been established.

Aims & Methods: We aimed to clarify the diagnostic yields of the two methods and predictive factors for a positive diagnosis.

We reviewed 241 patients with biliary strictures who underwent transpapillary brush cytology (n=202) and/or forceps biopsy (n=208) between 2004 and 2014 at a single academic center.

Results: The sensitivity of forceps biopsy for MBS was significantly higher than that of brush cytology (60.6% [97/160] vs. 36.1% [57/158]; P < 0.001). The sensitivity of forceps biopsy was significantly higher in bile duct cancer than pancreatic cancer (82.0% [50/61] vs. 42.4% [28/66]; P < 0.001). Multivariate analysis revealed that a serum total bilirubin level (T-Bil) ≥ 4 mg/dL (OR: 2.51, 95% CI: 1.14-5.50; p=0.022) was a significant independent predictive factor for a positive diagnosis by brush cytology, and bile duct cancer (OR: 4.93, 95% CI: 2.18-11.11; p < 0.001), length of stricture ≥ 30 mm (OR: 2.94, 95% CI: 1.12-7.75; p=0.029), and T-Bil ≥ 4 mg/dL (OR: 2.25, 95% CI: 1.05-4.83; p=0.037) were significant indicators of a positive diagnosis by forceps biopsy.

Conclusion: Endoscopic transpapillary forceps biopsy showed higher sensitivity than that of brush cytology for MBS. Bile duct cancer, length of stricture ≥ 30 mm and T-Bil ≥ 4 mg/dL are good indicators of a forceps biopsy.

Disclosure of Interest: None declared

MONDAY, OCTOBER 26, 2015   09:00-17:00

PANCREAS I – HALL 7__________

P0079 COPPER DEFICIENCY RESULTS IN PANCREATIC STELLATE CELLS ACTIVATION WITHOUT THEIR TRANSDIFFERENTIATION INTO MYOFIBROBLASTS

A. Galyavieva¹², A. Abdulkhakova¹, A. Trondin¹, G. Pevnev², M. Mavlikeev², S. Abdulkhakov¹², A. Gumerova², A. Kiassov²

¹Kazan State Medical University, ²Kazan (Volga region) Federal University, Kazan, Russian Federation

Introduction: Pancreatic stellate cells (PSCs) are supposed to play an important role in pancreatic fibrogenesis. However as they are quite common with hepatic stellate cells their role in pancreatic regeneration couldn’t be excluded.

Aims & Methods: The aim of our work was to study the role of PSCs in pancreatic tissue regeneration in rat copper-deficient diet model.

24 white Wistar male rats (80-100 g weight) were maintained on copper-deficient diet (MP Biomedicals, USA) containing a relatively non-toxic copper-chelating agent, triethylenetetramine tetrahydrochloride (Tokyo Chemical Industry Co., Ltd, Japan) in final concentration of 0.6% w/w for 8 weeks, and then returned to normal rat chow for another 8 weeks (recovery phase). Animals of control group were maintained on normal rat chow for the whole duration of experiment.

Groups of 3 animals each were killed after 2, 4, 6, and 8 weeks of copper-deficient diet and 2, 4, 6, and 8 weeks of recovery phase. Paraffin sections of pancreas were stained immunohistochemically using antibodies to desmin, a marker of PSCs, and alpha smooth muscular actin (a-SMA), a marker of myofibroblasts, which are supposed to be involved in pancreatic fibrogenesis.

Results: Signs of pancreatic acinar tissue injury were observed in rats after 4 weeks of copper-deficient diet. After 6 and 8 weeks of copper deficiency tissue was almost totally destroyed, however, few ducts and islets were still present; the similar pattern was observed 2 and 4 weeks after animals were returned to normal rat chow. Partial restoration of acinar tissue was observed by the 6 and 8 weeks of recovery phase.

Staining with antibodies to desmin revealed single desmin-positive cells located mainly around the blood vessels in control group animals. Similar results were found after 2 and 4 weeks of copper-deficient diet.

After 6 weeks of a diet intensive colouring of desmin-positive cells on periphery of islets was noted, the number of desmin-positive cells in acinar tissue increased. After 8 weeks of copper-deficient diet some desmin-positive cells located around blood vessels and ducts were observed along with the more intensive colouring of islet cells.

After rats were transferred to normal rat chow the number of desmin-positive cells slightly decreased. Along with the pale colouring of islets few desmin-positive stellate-shaped cells were found in islets and on the border of the existing islets and newly formed acinar tissue.

Staining with antibodies to a-SMA revealed only smooth muscle cells of blood vessels for the whole duration of the experiment.

Conclusion: The increased number of PSCs in areas of the newly formed acinar tissue probably reflects their participation in pancreas regeneration. However PSCs activation doesn’t result in their transdifferentiation into myofibroblasts thus not increasing the risk of pancreatic fibrosis.

Disclosure of Interest: None declared

P0080 PANCREATIC ISLET CELLS COULD BE THE SOURCE OF PANCREAS RESTORATION IN COPPER-DEFICIENT MODEL OF PANCREAS INJURY

A. Abdulkhakova¹, A. Galyavieva¹², A. Trondin¹, G. Pevnev², M. Mavlikeev², S. Abdulkhakov¹², A. Gumerova², A. Kiassov²

¹Kazan State Medical University, ²Kazan (Volga region) Federal University, Kazan, Russian Federation

Introduction: Few possible sources of pancreas regeneration including islet cells are discussed in literature.

Aims & Methods: The aim of our work was to study the phenotype of rat pancreatic islets cell in copper-deficient model of pancreas injury.

24 white Wistar male rats (80-100 g weight) were maintained on copper-deficient diet containing a copper-chelating agent, triethylene tetraminetetrahydrochloride, in final concentration of 0.6% w/w for 8 weeks, and then returned to normal rat chow for another 8 weeks. Control group animals were maintained on normal rat chow for the whole duration of experiment.

Groups of 3 animals each were killed after 2, 4, 6, and 8 weeks of copper-deficient diet and 2, 4, 6, and 8 weeks after return to normal rat chow. Paraffin sections of pancreas were stained immunohistochemically with antibodies to cytokeratin 19 (CK19), marker of pancreatic ducts cells, and alpha-fetoprotein (AFP), which is considered to be the marker of hepatoblasts as well as hepatocellular carcinoma cells.

Results: Both large ducts and small ductules between the acini stained with antibodies to CK19 were observed in pancreas sections in control group rats. No positive staining was found in pancreatic islets. Similar results were observed after 2 weeks of copper-deficient diet.

After 4 weeks of diet CK19-positve ducts as well as positive staining in central part of pancreatic islets was noted. After 6 and 8 weeks the number of CK19-positive cells and duct-like structures increased substantially, central part of islets was still CK19-positive.

After rats were transferred to normal rat chow the number of CK19-positive cells and ducts decreased, however, the central part of islets was positive until the end of the experiment.

The presence of CK19-positive cells in pancreatic islets was found recently in pancreas embryogenesis. So we suppose CK19-positive cells could be one of the steps of pancreatic stem cells differentiation in case of tissue recovery after injury.

Staining with antibodies to AFP was negative in normal pancreas as well as after 2 weeks of copper-deficient diet. After 4 weeks of diet solitary AFP-positive cells in acinar tissue were noted. After 6 and 8 weeks both single positive cells and duct-like structures as well as staining of central parts of pancreatic islets were observed.

After rats were transferred to normal rat chow the number of AFP-positive ducts decreased and disappeared by 8^th week, the cells of central part of islets remained positive until the end of the experiment.

Our results allow us to suppose that in the case of copper deficiency progenitor cells which could be common for liver and pancreas timely change their phenotype to hepatoblast-like cells, as described by Rao et al. (1989). However there is no possibility of oncogenic transformation as the number of AFP-positive cells decreased by the end of the experiment.

Conclusion: The abovementioned changes of CK19- and AFP-positive cells number allows us to suppose that pancreatic islet cells could be the source of pancreas regeneration. These progenitor cells are probably common for pancreas and liver and under certain conditions can express markers of hepatoblasts.

Disclosure of Interest: None declared

P0081 ADIPOSE TISSUE IS TOXIC FOR PANCREATIC PARENCHYMA: CO-CULTURE MODEL OF PANCREATIC TISSUE AND VISCERAL ADIPOSE TISSUE FROM OBESE PATIENTS

B. Jaïs¹², J. Cros¹, P. Bourgoin¹, S. Laouirem¹, M. le Gall¹, K. Arapis³, J.-P. Marmuse⁴, A. Sauvanet⁵, P. Ruszniewski², V. Paradis¹, P. Bedossa¹, A. Couvelard¹, V. Rebours²

¹Centre de recherche sur l'inflammation, INSERM-UMR 1149, Paris, ²Service de Pancréatologie Gastroentérologie, Hôpital Beaujon, Clichy, ³Service de Chirugie Digestive, ⁴Service de Chirurgie Digestive, Hopital Bichat, Paris, ⁵Service de chirurgie digestive, Hôpital Beaujon, Clichy, France

Contact E-mail Address: vinciane.rebours@bjn.aphp.fr

Introduction: Recently, obesity and metabolic syndrome have been identified as independent risk factors for chronic pancreatitis and pancreatic cancer. Visceral adipose tissue (VAT) of obese patients induces pro-inflammatory cytokines synthesis (TNF-α, IL- 6, adiponectin, leptin) known to be involved in pancreatic fibrogenesis by the activation of pancreatic stellate cells (PSC).

Aims & Methods

Aim: To study interactions between VAT from obese patients and ex-vivo pancreatic parenchyma by developing a co-culture model

Methods: We developed a 3D co-culture model. A slice of normal pancreas (300 μm) was cultured with 0.4g of VAT from obese patients embedded in a collagen gel layer. Culture was realized under normoxemic conditions (21% O2) and incubation time ranged from 24h to 48h. Morphological analysis of pancreas and VAT were performed at baseline, 24h and 48h. Cell differentiation (CK7, insulin), apoptosis (caspase 3), proliferation (Ki-67) and PSC activation (smooth muscle actin (SMA)) were assessed using immunostaining. Adiponectin and leptin were measured by ELISA method in the culture media. Control experiments were pancreas slice culture and VAT culture alone.

Results: 11 co-cultures were performed: 3 for 24h, 8 for 48h. Pancreatic necrosis at 24h and 48H were 30% [0- 70] and 37% [5-100] for pancreas culture versus 44% [0-80] and 62% [10- 100] for co-cultures, respectively. Necrosis was higher at 48h in co-cultures (p=0.024). In co-cultures, we observed an increase of 1/ SMA expression in PSC, 2/ number of duct cells in apoptosis or proliferation, 3/ insulin expression in the Langerhans islets. Leptin and adiponectin concentrations were high in VAT culture and very low in pancreas culture. After 24h of co-culture, adiponectin concentration decreased in co-cultures compared to VAT culture (p=0.016). At 24h and 48h of co-culture, leptin concentration compared to VAT culture decreased (p < 0.05).

Conclusion: This model is the first co-culture model between VAT and human pancreas tissue. It validated the lipotoxic role of VAT from obese patients on pancreatic tissue by altering pancreatic cells population (duct cells, Langerhans islet, PSC). It obtained reproducible results and was able to underline the interactions between these two tissues through the cytokines secretions. This new method could permit to clarify the physiopathology of obesity and metabolic syndrome in pancreatic diseases.

Disclosure of Interest: None declared

P0082 PANCREATIC EXOCRINE FUNCTION IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

D. Illés¹, G. Zsóri¹, V. Terzin¹, G. Holzinger², K. Kosár², L. Czakó¹

¹First Department of Internal Medicine, ²University of Szeged, Szeged, Hungary

Contact E-mail Address: olionx@gmail.com

Introduction: An exocrine pancreatic insufficiency has been demonstrated to be present in about 50% of type 1 and 30- 50% of type 2 diabetes mellitus (T2DM) cases. However, the significance of an exocrine pancreatic dysfunction in DM has recently been questioned.

Aims & Methods: The aim of our study was to assess the prevalence of exocrine pancreatic dysfunction in T2DM.

Methods: Consecutive patients with type 2 DM treated in our clinic were prospectively recruited into the study. Exocrine pancreatic insufficiency was diagnosed by fecal elastase-1 (FE1) determination. All patients underwent abdominal ultrasound and pancreatic diabetes cases were excluded.

Results: One hundred eighty four patients (91 male, 93 female, mean age 61.74 ± 17 years) were recruited in the study. FE1 was abnormal in 37 patients, 12 patients had non-insulin treated T2DM and 25 patients insulin-treated T2DM. The severity of exocrine insufficiency was mild in 29 and severe in 8 patients. The FE1 level was not correlated with HbA1c (p=0.487), the duration of DM (p=0.88), age (p=0.907), BMI (p=0.157), pancreatic steatosis (p=0.528) or the presence of microvascular complications of DM (p=0.465).

Conclusion: Exocrine pancreatic insufficiency is less frequent in type 2 DM, than in previous study, probably because pancreatic diabetes cases were excluded. Exocrine pancreatic insufficiency was not associated with the duration of DM, BMI, HbA1c level, pancreatic steatosis or the presence of microvascular complications of DM.

Disclosure of Interest: None declared

P0083 BETAINE ATTENUATES ALCOHOLIC PANCREATIC STEATOSIS THROUGH DOWN-REGULATION OF STEROL REGULATORY ELEMENT BINDING PROTEIN-1C

W.-J. Yang¹, J. Li¹, J.-H. Gao¹, Z.-Y. Huang¹, C.-W. Tang¹

¹Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China

Contact E-mail Address: yangwenjuan19860@163.com

Introduction: Growing studies have shown that chronic alcohol consumption caused pancreatic steatosis. However, medical interventions for alcoholic pancreatic steatosis have not been extensively investigated. Betaine was found to alleviate alcoholic fatty liver disease in multiple studies. In the present study, we investigated the effect of betaine on alcoholic pancreatic steatosis and its mechanism.

Aims & Methods: 45 male Wistar rats were randomized into control, alcohol and alcohol + betaine group with 15 animals in each group. Rats in the three groups were given free access to distilled water, ethanol (25%, v/v) and ethanol (25%, v/v) plus betaine (1%, w/v), respectively, for six months. Morphological changes of the pancreatic acinar cells were identified by hematoxylin-eosin staining, oil red O staining and transmission electron microscope. Pancreatic triglyceride (TG) and total cholesterol (TC) contents were measured by enzymatic colorimetric assay. Serum adiponectin levels were determined by enzyme-linked immunosorbent assay. The protein and mRNA expression of pancreatic adiponectin receptor-1 (AdipoR1), AdipoR2, sterol regulatory element binding proteins-1c (SREBP-1c), and SREBP-2 were determined by immunohistochemistry (IHC), Western blot (WB) and quantitative real-time PCR (qRT-PCR). The effect of betaine (168 mmol/L) and/or adiponectin (0.5 μg/mL) on SREBP-1c expression in ethanol-treated (100 mmol/L) SW1990 pancreatic adenocarcinoma cells was also assessed by WB and qRT-PCR.

Results: Alcohol-induced morphological changes of the pancreatic acinar cells, including lipid droplets, swelling mitochondria and reduced zymogen granules, were attenuated after betaine treatment. Compared with control group, pancreatic TG level in ethanol group was markedly increased by 90.5% (P<0.01). Interestingly, betaine treatment dramatically reduced pancreatic TG level of alcoholic rats by 39.3% (P<0.05). However, pancreatic TC content was similar among the three groups (P>0.05). Serum adiponectin level in alcohol-fed rats was significantly decreased by 66.5% (P<0.01) when compared to that in control group and was greatly increased by 148.6% after treatment with betaine (P<0.01). Immunohistochemical staining showed that pancreatic AdipoR1 expression was dramatically down-regulated after ethanol exposure and was up-regulated to control level after betaine treatment. Moreover, pancreatic SREBP-1c expression was elevated in alcohol group but remained at control level after treatment with betaine. Nevertheless, no significant difference was shown in pancreatic AdipoR2 and SREBP-2 expression by IHC among the three groups. The immunohistochemical staining results were further confirmed by qRT-PCR and WB. In vitro, betaine or/and adiponectin significantly suppressed up-expression of SREBP-1c induced by ethanol with the maximum inhibitory effect achieved when they were given in combination.

Conclusion: Betaine attenuated alcohol-induced pancreatic steatosis probably by suppressing SREBP-1c activation and this effect of betaine was partly attributed to the restoration of pancreatic adiponectin signaling as well as the direct action of betaine on pancreatic SREBP-1c.

Disclosure of Interest: None declared

P0084 CELL DAMAGE INDUCED BY CHENODEOXYCHOLATE ON PANCREATIC DUCTAL EPITHELIAL CELLS CAN BE AMELIORIATED BY URSODEOXYCHOLATE PRETREATMENT

M. Katona¹, P. Hegyi¹, Z. Rakonczay Jr.¹, E. S. Kormányos¹, Z. Balla¹, B. Kui¹, J. Maléth¹, Z. Rázga², V. Viktória³

¹First Department of Medicine, ²Department of Pathology, ³Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary

Contact E-mail Address: mate.katona@gmail.com

Introduction: Our previous results showed that high concentration of chenodeoxycholate (CDC) strongly inhibits ion transporters via destruction of mitochondrial function in guinea pig pancreatic ductal epithelial cells (PDECs). Ursodeoxycholic acid (UDC) has been reported to protect mitochondria against hydrophobic bile acids and have antiapoptotic effect.

Aims & Methods: The aim of this study was to investigate the effect of UDC on CDC-induced cell damage.

Intra-interlobular ducts were isolated from the pancreas of guinea pig. Ducts were then pretreated with UDC (0.1 mM and 0.5mM) for 5 h and 24 h and changes in intracellular Ca²⁺concentration [Ca²⁺]_i, ATP level [ATP]_i, pH [pH]_i and mitochondrial permeability transition pore (MPTP) opening were measured by microfluorometry. Mitochondrial transmembrane potential (MTP) was studied by confocal microscopy. Expressions of bile acid transporters were analysed by reverse transcriptase PCR (RT-PCR). Morphological changes of mitochondria were investigated by transmission electron microscopy. We also developed a CDC induced pancreatitis model in rats. Rats were fed with 250 mg/kg UDCA for 2 weeks then pancreatitis was induced by intraductal administration of 0.1% CDC.

Results: 5 h pretreatment with 0.1 or 0.5 mM UDC and 24 h pretreatment with 0.1 mM UDC did not significantly influence the effect of 1 mM CDC on duct cells. However, 24 h pretreatment with 0.5 mM UDC significantly reduced the rate of ATP depletion, mitochondrial injury, MPTP opening and the decrease of MTP induced by 1 mM CDC. In addition, 0.5 mM UDC prevented the inhibitory effect of CDC on the acid-base transporters, however, had no effect on the CDC-induced calcium signaling. mRNA expression of Slc10A1 and A2 was detected in the ducts by RT-PCR. Animal experiments showed, that UDCA fed group had less severe pancreatitis in CDC induced pancreatitis model.

Conclusion: Our results indicate that UDC administration protects the bile-induced mitochondrial injury which may represent a novel therapeutic option in pancreatitis.

This study was supported by

Hungarian National Development Agency grants (TÁMOP-4.2.2.A-11/1/KONV-2012-0035

TÁMOP-4.2.2-A-11/1/KONV-2012-0052,

TÁMOP-4.2.2.A-11/1/KONV-2012-0073, TÁMOP-4.2.2./B-10/1-2010-0012, TÁMOP 4.2.4.A/2-11-1-2012-0001 ‘National Excellence Program) and the Hungarian Scientific Research Fund (OTKA NF105758, NF100677, K109756)

Disclosure of Interest: None declared

P0085 ANALYSIS OF THE STRUCTURAL AND SENSORY INNERVATION IN THE MOUSE PANCREAS

Ö. C. Saricaoglu¹, I. E. Demir¹, H. Friess¹, G. O. Ceyhan¹

¹Department of Surgery, Klinikum rechts der Isar, TU München, München, Germany

Contact E-mail Address: drocesar@gmail.com

Introduction: Human pancreatic cancer/PCa and chronic pancreatitis/CP are characterized by neural hypertrophy, neural sprouting, and reduced sympathetic innervation. However, our knowledge on the innervation of current murine models of PCa and CP and even of normal mouse pancreas is very scarce.

Aims & Methods: In this study, we aimed to systematically analyze the structure, distribution and quality of nerves in the mouse pancreas. Whole pancreata derived from 6-8-week-old C57BL/6J mice (n=10) were paraffin-embedded and entirely sectioned into 3µm consecutive sections from the anterior to the posterior/retroperitoneal plane. All sections were immunostained with the pan-neural-marker PGP 9.5, with the sensory fibre markers substance-P/SP and calcitonin-gene-related-peptide/CGRP and were subject to systematic morphometric analysis.

Results: Nerves enter the mouse pancreas around pericapsular lymphoid structures and penetrate into the tissue along vessels and interlobular septae. The size and the density of nerves in the pancreatic head and corpus were significantly greater than in the pancreatic tail. The majority of nerves were localized in the anterior and posterior surface of the head and the anterior surface of the corpus. The proportion of sensory fibres was ca. 8% of all nerve fibres in the mouse pancreas and did not vary between the head, corpus and tail. 74% of sensory fibres were localized in the pancreatic head, 19% in the corpus and 7% in the tail.

Conclusion: Murine pancreatic head has the highest density of pancreatic nerves. Overall, due to its intraperitoneal and perilymphoid localization, the mouse pancreas bears a substantially different structural innervation pattern when compared to the human pancreas.

Disclosure of Interest: None declared

P0086 FLUID AND HCO3- SECRETION AND CFTR ACTIVITY ARE INHIBITED BY CIGARETTE SMOKE EXTRACT IN GUINEA PIG PANCREATIC DUCTAL CELLS

P. Pallagi¹, V. Venglovecz², E. Gál¹, K. Tóth¹, A. Schnúr¹, J. Maléth¹, D. Csupor³, Z. Rakonczay¹, P. Hegyi¹

¹First Department of Medicine, ²Department of Pharmacology and Pharmacotherapy, ³Department of Pharmacognosy, University of Szeged, Szeged, Hungary

Contact E-mail Address: pallagi.petra&gmail.com

Introduction: Smoking represents an independent risk factor for the development of chronic pancreatitis (CP). It is well documented that secretion of pancreatic ductal alkaline fluid (which is regulated mostly by the anion exchanger and CFTR) is diminished in CP. In this study we would like to understand whether smoking has any effects on pancreatic ductal fluid and HCO₃^- secretion.

Aims & Methods: Intra/interlobular pancreatic ducts were isolated from guinea pig pancreas. Cigarette smoke extract (CSE) was prepared by smoking of 30 cigarettes into 20ml distilled water by a smoking machine. Three different doses (20, 40 and 80µg/ml) were diluted using the stock solution. Basal and forskolin-stimulated fluid secretion was measured by video microscopy. Intracellular pH and Ca²⁺ concentration were evaluated by microfluorometry. Luminal anion exchange activity was determined by the chloride withdrawal technique using microperfusion. CFTR currents were detected by whole-cell configuration of patch clamp technique.

Results: CSE dose dependently decreased forskolin-stimulated fluid secretion in guinea pig pancreatic ducts, bicarbonate secretion (20µg/ml by 17.3%, 40µg/ml by 40.5%) and forskolin-stimulated Cl^- current of CFTR Cl^- channel (20µg/ml by 44.5%, 40µg/ml by 69.3% and 80µg/ml by 81.3%). Moreover, CSE induced dose-dependent intracellular calcium elevation suggesting that some of the inhibitory effects may be regulated by calcium signalling.

Conclusion: CSE inhibits pancreatic ductal fluid and HCO₃^- secretion and the activity of the CFTR which may play role in the smoke-induced pancreatic damage. This study was supported by OTKA, MTA and NFÜ/TÁMOP.

Disclosure of Interest: None declared

P0087 ABSENCE OF SEROTONIN SIGNIFICANTLY ELEVATES PANCREATIC EPITHELIAL FLUID AND BICARBONATE SECRETION IN MICE

T. Madacsy¹, J. Maléth¹, P. Pallagi¹, A. Balázs¹, V. Venglovecz², Z. Rakonczay Jr.¹, P. Hegyi¹

¹Ist Department of Medicine, ²Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary

Contact E-mail Address: tamaramadacsy@gmail.com

Introduction: Serotonin (5-hydroxytryptamine, 5-HT) is a potent bioactive molecule, which regulates zymogen secretion in pancreatic acinar cells and inhibits pancreatic ductal epithelial secretion. Recently it was demonstrated that tryptophan hydoxylase-1 (TPH-1) knock-out mice, which lack peripheral 5-HT, develop less severe acute pancreatitis (AP) compared to wild type (WT) controls. Decreased pancreatic fluid and bicarbonate secretion can lead to more severe AP, however the pancreatic ductal secretion of TPH-1 knock-out mice has not been evaluated, which might contribute to the protection against AP.

Aims & Methods: Our aim was to evaluate the pancreatic ductal secretion in TPH-1 knock-out and WT mice.

Intra/interlobular pancreatic ducts were isolated from the pancreas of TPH-1 knockout and WT mice. In vitro pancreatic ductal fluid secretion has been evaluated using videomicroscopy. Bicarbonate secretion of pancreatic ductal epithelial cells was measured by microfluorimetry.

Results: In vitro pancreatic ductal fluid secretion was significantly elevated in TPH-1 knock-out mice compared to WT controls. Basolateral administration of 20mM NH₄Cl revealed that the activities of the apical Cl^-/HCO₃^- exchanger (CBE) and the basolateral Na⁺/HCO₃^- cotransporter and Na⁺/H⁺ exchanger were significantly elevated in TPH-1 knock-out mice. The acidification caused by basolateral administration of dihydro-4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (H₂DIDS) and amiloride was markedly increased in TPH-1 knock-out mice confirming the increased activity of the apical HCO₃^- secretion. The administration of serotonin significantly decreased the activity of the acid/base transporters in TPH-1 knock-out and WT ductal epithelial cells. As a further step we provided evidence that the Cl-/HCO3- exchanger is crucially important in the elevated ductal secretory process important in the elevated ductal secretory processesion, since. T the rate of pHi recovery was significantly elevated in TPH1-/- mice from the intracellular alkalization-caused byafter Cl-withdrawal from the lumeinal space of the microperfused pancreatic ducts

since the rate of pHi recovery significantly elevated in TPH1-/- mice from the intracellular alkalization-caused by Cl- withdrawal from the luminal space of the microperfused pancreatic ducts.

Conclusion: These findings indicate that the fluid and bicarbonate secretion is significantly increased in the absence of serotonin, which might contribute to the decreased severity of AP in TPH-1 knock-out mice.

Disclosure of Interest: None declared

P0088 VITAL IMPORTANCE OF THE DISSEMINATION OF IAP/APA GUIDELINES: DRAMATIC RESULTS DURING THE VALIDATION STUDY ON A NATIONWIDE COHORT

A. Párniczky¹,*, I. Hritz², A. Balázs³, S. Gódi⁴, A. Halász⁵, B. Kui⁶, D. Mosztbacher⁷, Á. Szűcs⁸, J. Sümegi⁹, B. Bod¹⁰, J. Novák¹¹, S. Crai¹¹, J. Hamvas¹², T. Kiss¹², M. Varga¹³, K. Csefkó¹⁴, P. Sarlós¹⁵, J. Bajor⁴, I. Szabó⁴, F. Izbéki¹⁶, J. Gervain¹⁷, T. Takács¹⁸, L. Czakó¹⁸, Z. Szepes¹⁸, R. Bor¹⁸, V. Szidor¹⁹, P. Hegyi²⁰ on behalf of Hungarian Pancreatic Study Group

¹Heim Pál Children's Hospital, Budapest, ²Bács-Kiskun County University Teaching Hospital, Kecskemét, ³First Department of Medicine, University of Szeged, Szeged, ⁴First Department of Medicine, University of Pécs, Pécs, ⁵First Department of Medicine,, Szent György University Teaching Hospital of County Fejé, Székesfehérvár, ⁶First Department of Medicine, University of Szeged, Szeged, ⁷ Department of Pediatrics, János Balassa County Hospital, Szekszárd, ⁸First Department of Surgery,, Semmelweis University,, Budapest, ⁹Borsod-Abaúj-Zemplén County Hospital and University Teaching Hospital, Miskolc, ¹⁰Dr. Bugyi István Hospital, Szentes, ¹¹Pándy Kálmán County Hospital, Gyula, ¹²Bajcsy-Zsilinszky Hospital, Budapest, ¹³Réthy Pál Hospital, ¹⁴Dr. Réthy Pál Hospital, Békéscsaba, ¹⁵First Department of Medicine, University of Pécs, Pécs, ¹⁶First Department of Medicine, Szent György University Teaching Hospital of County Fejér, Székesfehárvár, ¹⁷First Department of Medicine, Szent György University Teaching Hospital of County Fejér, Székesfehérvár, ¹⁸First Department of Medicine,, University of Szeged, ¹⁹First Department of Medicine, University of Szeged, ²⁰First Department of Medicine,University of Szeged, Hungarian Academy of Sciences,Momentum Translational Gastroenterology Research Group, Szeged, Szeged, Hungary

Contact E-mail Address: andrea.parniczky@gmail.com

Introduction: The IAP/APA evidence-based (EBM) guidelines for the management of acute pancreatitis(AP) have been published in 2013. Unfortunately in many countries, especially in Eastern and Central Europe, it has not been translated to national languages and no EBM guidelines are available so far. The Hungarian Pancreatic Study Group (HPSG) has established a national registry in 2011 for prospective data collection of patients suffering from different pancreatic disorders,including AP.

Aims & Methods: Our aim was to summarize the Hungarian cohort and importantly, assess and validate the usefulness of the IAP/APA guidelines. 580 patients with AP have been enrolled from 23 centers.

Results: The diagnosis of AP was made according to the 2/3 rule. 322 males and 258 females with mean age of 58.4 ± 16.5 were enrolled.The most common cause of AP was biliary disease (44%)followed by regular alcohol consumption or dietary mistake (26%). 61.9% of the patients had mild, 29.6% moderate, whereas 8.5% severe pancreatitis. Concerning the intravenous fluid therapy, only 41% of the patients received 2500-4000 ml of fluids during the first 24 hours.The mortality was only 0.51% in this group, however, it was increased by 4 times among those patients who received either more or less fluid. In terms of the enteral feeding, 31% of patients with severe pancreatitis did not receive it. The mortality rate in this group was unacceptably high(42.9%) compared to those patients who received the right treatment(19.3%).

Conclusion: Proper utilization of the IAP/APA EBM guidelines could save thousands of lives. It is vitally important to make the guidelines available in all languages of the countries.

Disclosure of Interest: None declared

P0089 EARLY DIFFERENTIAL DIAGNOSIS OF MILD ACUTE PANCREATITIS FROM MORE SEVERE FORMS

A. I. Ershova¹², A. V. Popov¹², D. A. Mineev³, N. N. Popova¹

¹Hospital surgery, Perm State Medical University, ²Laboratory of Physical hydrodynamics, Institute of Continuous Media Mechanics, Ural Branch of Russian Academy of Science, ³General Surgery, Perm State Medical University, Perm, Russian Federation

Contact E-mail Address: ershovaa@inbox.ru

Introduction: Acute pancreatitis (AP) is characterized by a wide range of clinical courses, varying from interstitial edema to pancreatic necrosis. This determines the relevance of simple and fast criteria for early detection of the disease severity.

Aims & Methods: The aim is to determine the effectiveness of rating scales for early stratification of AP. The severity of patient's condition was estimated in 24 hours with the help of such rating scales as BISAP, HAPS, SOFA, SIRS, US scale [1]. The severity of AP was detected in accordance with the classification of Atlanta 2012 in 48-72 hours. Balthazar-Ranson scale was used at the same time period. ROC-analysis of the scales was performed with the calculation of the area under the operating characteristic curve (AUC).

Results: There were 61 patients with AP (mean age 44.0 ± 1.7, 57.3% male), of which 24.7% were classified as mild, 34.4% as moderate & 40.9% as severe. Determination of mild AP according to the BISAP ≤ 1 и US scale ≤ 3 was characterized by high accuracy (AUC (95% confidence interval) 0.77 (0.66–0.87) & 0.90 (0.82–0.98) respectively), sensitivity (71.1 & 81.0% respectively) and negative predictive value (48.0 & 66.6% respectively). The scales HAPS ≤ 1, SOFA ≤ 3 and SIRS ≤ 1 had smaller AUC (p < 0.05) (0.62; 0.62 & 0.66 respectively), lower quality of determining of mild AP (60.0; 68.8 & 51.1% sensitivity respectively). They also had smaller negative predictive value (35.7; 36.6 & 35.2% respectively).

Conclusion: The BISAP scale and US scale are reliable methods for early detection of mild AP (in 24 hours). Their high positive prognostic values (81.6 & 88.8%) allow to identify on early stage the patients that are not needed intensive care. This could save significant costs for the hospital.

Disclosure of Interest: None declared

P0090 SEVERITY PATTERN OF RECURRENT ACUTE PANCREATITIS. IS IT STABLE?

F. Bende¹, I. Sporea¹, A. Popescu¹, R. Sirli¹, R. Pleava¹

¹Gastroenterology and Hepatology, University of Medicine and Farmacy “Victor Babes” Timisoara, Timisoara, Romania

Contact E-mail Address: bendefelix@gmail.com

Introduction: Acute pancreatitis (AP) varies from mild, to moderately-severe and severe forms, the last with complications and high mortality rate. Knowledge of its natural course and recurrence is limited.

Aims & Methods: The aim of this study was to evaluate the severity pattern of recurrent AP and compare the clinical outcomes to those with a single episode.

We performed a retrospective study on 1079 patients (58.7% male, 41.3% female) with mean age of 55 ± 16 years old admitted in our unit from 2006 to 2014 with acute pancreatitis. We compared patients with recurrent AP to those who had a single episode. We looked to the mortality, the severity of AP, the trend of the recurrences and made an overview analysis.

Results: In the 9-year analysis, 995 patients (92.2%) were admitted with a single episode of AP and 84 (7.8%) patients had a recurrent form. The readmissions varied from 2 episodes in most cases (78.5%) to 3(13.1%), 4 (4.8%), 5(1.2%) and 6 episodes (2.4%). The severity pattern for the majority of AP readmission was mostly unchanged, 70% of them presented at recurrences a similar form with the initial episode, 14% had a worse outcome and 16% had a milder form. The mortality rate in patients experiencing a single episode of AP was 3.7%, as compared to 0% in patients with recurrent AP (p= 0.0096). Recurrent episodes of AP seem to be protective against multiple organ failure (odds ratio 0.056, 95% CI 0.0034-0.928, p=0.0442). Regarding the etiology, in patients that had only 2 recurrences the most common cause was biliary (50.7%) followed by alcohol (33.8%) and other etiologies (15.5%) whereas in patients with 3 or more recurrences, the predominant cause was alcohol (66%) as compare to non-alcoholic etiologies (33%).

Conclusion: Patients that have recurrent form of AP seem to have lower risk of clinically severe course. The severity pattern remains stable in most cases of recurrent AP. Furthermore, the mortality of these patients seems to be lower as compared to that of patients with a single episode of AP.

Disclosure of Interest: None declared

P0091 IMIPENEM PROPHYLAXIS FOR PREDICTED SEVERE ACUTE PANCREATITIS - PRELIMINARY RESULTS OF A RANDOMIZED CLINICAL TRIAL

G. Poropat¹, V. Giljaca¹, V. Licul¹, G. Hauser¹, S. Milic¹, D. Stimac¹

¹Department of Gastroenterology, University Hospital Rijeka, Rijeka, Croatia

Introduction: Infected necrosis is a serious complication of acute pancreatitis leading to a mortality rate of about 40%¹. Although prophylactic antibiotics are not recommended, meta-analytic data show that imipenem significantly reduces the rate of infected necrosis¹.

Aims & Methods: The aim of our study is to evaluate the prophylactic use of imipenem in patients with predicted severe acute pancreatitis. We conducted a prospective randomized trial in a tertiary care setting in Rijeka. Patients with AP and an APACHE II ≥ 8 were randomized to receive either imipenem 500 mg i.v. three times daily for the first ten days or an identical placebo. Exclusion criteria included age < 18 years, any infection present at admission, chronic pancreatitis, active malignancy, immunodeficiency, post-surgical patients, pregnant and breastfeeding women and patients unwilling to participate in the study. All patients received early enteral nutrition administered via a nasojejunal tube. Concomitant treatment was similar in both groups. All patients had an abdominal CT scan performed between days 3 to 7, and in cases of clinically suspected infected pancreatic necrosis.

Results: Forty-seven consecutive patients were randomized. Twenty-three received imipenem and 24 received placebo. Three patients died in the imipenem group, while two patients died in the placebo group (p=0.667). There were no differences in the occurrence of infected necrosis, with 2 vs. 3 cases, respectively. Other local complications were present in 7 and 13 patients (p=0.142), while persistent organ failure was present in 4 and 5 patients (p=1.00) in the imipenem and placebo group, respectively. Other infection were detected in 2 patients receiving imipenem and 5 patients on placebo (p=0.416).

Conclusion: Preliminary data showed no significant beneficial effects of prophylactic imipenem use in patients with predicted severe acute pancreatitis.

Disclosure of Interest: None declared

P0092 A SYSTEMATIC REVIEW OF ENTERAL NUTRITION FORMULATIONS FOR ACUTE PANCREATITIS

G. Poropat¹, V. Giljaca¹, G. Hauser¹, D. Stimac¹

¹Department of Gastroenterology, University Hospital Rijeka, Rijeka, Croatia

Introduction: Acute pancreatitis (AP) is a common disease with increasing incidence. Severe cases are characterized with high mortality and despite improvements in intensive care management, there is still no specific treatment that relevantly benefits clinical outcome.

Aims & Methods: To assess effects of different enteral nutrition (EN) formulations in patients with AP. We conducted searches of Medline, Embase, Central, and SCI-E for RCTs assessing use of a specific EN formula compared to control (other EN formula, TPN, placebo, or no intervention). We assessed the following outcomes: mortality, organ failure, and local septic complications (LSC).

Results: Twenty-five RCTs with a total of 1979 patients were included. Immunonutrition significantly decreased mortality (P=0.005), but subgroup analysis comparing immunonutrition to another EN did not confirm this finding. Probiotics did not confirm any significant effect, however sensitivity analysis by exclusion of one trial with inconsistent results showed decrease in mortality (P=0.02) and LSC (P=0.002), but not organ failure. Semi-elemental EN reduced mortality (P=0.002), organ failure (P < 0.00001), and LSC (P < 0.00001). Few trials evaluated polymeric and fibre-enriched formulas, showing no significant effect. Any EN compared to TPN confirmed reduced mortality (P < 0.0001), organ failure (P < 0.00001) and LSC (P < 0.00001), and any EN compared to no intervention was associated with lower mortality (P=0.01).

Conclusion: Whether supplementation of EN with potential immunomodulatory agents leads to beneficial effects is still debatable. Studies assessing probiotics yielded inconsistent results, therefore we do not support the routine use of these formulations in clinical practice, but further research is required. EN is significantly more efficient than TPN and no nutritional support.

Disclosure of Interest: None declared

P0093 LOW MOLECULAR WEIGHT HEPARIN TREATMENT OF ACUTE SEVERE PANCREATITIS: A RANDOMIZED, CONTROLLED STUDY

H. Senturk¹, M. Tozlu¹, Y. Kayar¹, B. Baysal¹, A. T. Ince¹, A. Danalioglu¹

¹Department of Internal Medicine, Division of Gastroenterology, Bezmialem Vakif University, Istanbul, Turkey

Contact E-mail Address: ykayar@yahoo.com

Introduction: Severe acute pancreatitis which constitutes 20-30% of all acute pancreatitis, may cause pancreatic necrosis, persistent organ failure and mortality. Beginning and progression of acute pancreatitis is accompanied with systemic inflammatory cascade activation and pancreatic microcirculation disturbance. Heparin inhibits inflammatory cascade, and improves pancreatic microcirculation. The purpose of this study is to determine the effect of low molecular weight heparin (LMWH) in the prevention of pancreatic necrosis in severe acute pancreatitis.

Aims & Methods: A total of sixty-eight moderately severe and severe acute pancreatitis patients were randomised to receive conventional therapy or conventional therapy plus LMWH therapy. LMWH was administrated 1 mg/kg by subcutaneous injection two times per day between 1th and 7th days. Revised Atlanta criteria are used in the diagnosis. Imrie Score, HAPS (Harmless Acute Pancreatitis Score), Balthazar computed tomography (CT) score are evaluated. Patients with coagulation disorders, severe comorbidities, using clopidogrel or warfarin, under hemodialysis, pregnant and lactating women are excluded.

Results: The mean age ± SD of the patients (31 male and 37 female) were 52.1 ± 19.7 years (range; 17-100 years). There were 34 (50%) patients in the LMWH group and 34 (50%) patients in the control group. The etiology of these patients included biliary diseases in 43 patients (63.2%), hyperlipidemia in 4 (5.9%), and other in 9 (13.3%). Etiology can not be defined in 12 (17.6%), On admission, all the clinical and laboratory parameters and Balthazar CT score in the two groups were similar. After one week of follow-up, pancreatic necrosis developed in 3 (8.8%) patients in the LMWH group and 9 (26.4%) in the control group (p:0.049). Complications were observed in 6 (17.6%) patients of LMWH group and 11 (32.4%) patients of controls group. No haemorrhagic complications occurred. Three patients died in the control group, while no death occured in LMWH group (p: 0.072).

Conclusion: LMWH treatment is safe and provides a tendency for better prognosis in severe acute pancreatitis.

Disclosure of Interest: None declared

P0094 HEMORRHAGE COMPLICATING THE COURSE OF SEVERE ACUTE PANCREATITIS

P. Krishna¹, V. Gupta¹, H. S. Dhaliwal², S. K. Sinha¹, T. D. Yadav¹, A. Bhalla¹, R. Kochhar¹

¹Post graduate Institute of Medical Education and Research, Chandigarh, India, ²Post graduate Institute of Medical Education and Research, Chandigarh, India

Contact E-mail Address: dr_kochhar@hotmail.com

Introduction: Course of severe acute pancreatitis (SAP) can be complicated by hemorrhage, which is associated with poor outcome.

Aims & Methods: 183 patients (mean age 39.6 ± 13 years, M:F 2.6:1) of SAP were evaluated prospectively (n = 86) and retrospectively (n =97) for hemorrhagic complications. Hemorrhagic complications were categorised based upon the site (luminal or intra-abdominal), timing (occurring prior to or after an intervention) and severity (minor or major, depending on the need for blood transfusion). Data was analysed using SPSS version 22 and outcome measures studied were predictors of bleed, mortality and final outcome.

Results: 24 (13.1%) patients had hemorrhagic complications; 12 intra-abdominal and 12 intraluminal. 13 had a major and 11 had minor bleed; 16 patients bled before and 8 after intervention (radiological 3, surgical 5). The mean duration of pancreatitis prior to bleed was 27.0 ± 27.2 days. Predictors of bleed on univariate analysis were male sex (p = 0.014), organ failure (p = 0.008), venous thrombosis (p = 0.033), infected necrosis (0.001) and systemic sepsis (0.037). On multivariate analysis, infected necrosis (p = 0.015, OR 5.55) was a significant risk factor. Radiological drainage was associated with decreased risk of bleeding (45.8% vs 54.4%; p = 0.000). Need for surgery (50% vs 12.6%, p = 0.003), intensive care stay (7.4 ± 7.9 vs 5.4 ± 5.2 days; p = 0.001) and mortality (41.7% vs 10.7%; p = 0.000) were significantly higher in bleeders. 7/13 of major bleeders had pseudoaneurysms. 4/12 with luminal bleed had hollow viscus erosion, all needed surgery. CT severity index and surgical intervention, were significantly associated with intra-abdominal bleed. 7/12 intra-abdominal bleeders required surgical intervention. Organ failure, presence of pseudoaneurysm and surgical intervention were associated with major bleed. No significant factor could be identified for post-intervention bleed.

Conclusion: Infected necrosis predisposes to hemorrhage. Luminal bleed may be indicative of erosion into the adjacent viscera. Pseudoaneurysms were associated with major bleeding.

Disclosure of Interest: None declared

P0095 IRON METABOLISM AND OXIDATIVE STRESS IN ACUTE PANCREATITIS PATIENTS

I. Kuliaviene¹, Z. Dambrauskas², A. Gulbinas², J. Pundzius², E. Jansen³, L. Kupcinskas¹

¹Gastroenterology, ²Surgery, Lithuanian University of Health Sciences, Kaunas, Lithuania, ³Laboratory of Health Protection Research, National Institution for Public Health Sciences, Bilthoven, Netherlands

Contact E-mail Address: irma.kuliaviene@gmail.com

Introduction: It is suggested that oxidative stress (OS) may play a role in the development of pancreatic injury and systemic complications during acute pancreatitis (AP). Iron is one of important payers in the redox state. The data about iron metabolism and its role during AP is limited to some experimental findings. To our knowledge this study is the first evaluating the disturbance of iron metabolism as well as its associations with oxidative stress in the early phase of AP.

Aims & Methods: The study was addressed to find out possible disturbances of iron metabolism and its interactions with oxidative stress during the early phase of acute pancreatitis. Blood samples were collected from patients with mild (n=22) and severe (n=17) AP, and a group of healthy individuals (n=26). Serum oxidative stress markers measured in serum included Reactive Oxygen Metabolites (ROM) and Ferric Reducing Antioxidant Power (FRAP), Total Oxidative Capacity (TOC) and Total Antioxidative Capacity (TAC). Serum ferritin, iron (Fe) and transferrin were measured and the iron saturation of transferrin (TS) was calculated.

Results: A disturbed iron status in all pancreatitis groups was found. Iron, transferrin and the iron saturation of transferrin were significantly lower and ferritin was significantly higher in all AP groups. The serum oxidative stress parameters reflecting the lipid peroxidation process ROM and TOC showed significantly decreased levels in the AP group as well as mild and severe AP groups comparing to controls. TOC decreased more in mild AP patients than in severe AP patients, the difference was significant. One of the measurements of total antioxidant capacity (FRAP) was increased in all AP groups, compared with the control group. TAC showed no significant changes in the groups. There was a significant correlation between ROM with transferrin (Spearman’s correlation coefficient 0.44, p=0.00) and with ferritin (Spearman’s correlation coefficient 0.32, p=0.008), between FRAP and transferrin (Spearman’s correlation coefficient 0.38, p=0.001) and ferritin (Spearman’s correlation coefficient 0.52, p=0.000). There was a significant correlation between TOC and TS (Spearman’s correlation coefficient 0.352, p=0.006) as well as TOC and Fe (Spearman’s correlation coefficient 0.346, p=0.007).

Abstract number: P0095

	AP	Severe AP	Mild AP	Control
Fe Transferrin	6.44 ± 5.44* 1.69 ± 0.45*	7.33 ± 6.03* 1.61 ± 0.43*	5.74 ± 4.98* 1.76 ± 0.46*	20.81 ± 7.47 2.60 ± 0.42
Ferritin TS	518.32 ± 277.39* 16.74 ± 18.78*	603.20 ± 281.82* 21.51 ± 25.87#	451.32 ± 261.82* 12.97 ± 9.61*	118.11 ± 94.38 32.56 ± 12.81
ROM TOC	239.91 ± 142.17* 0.05 ± 0.06*	219.77 ± 150.85# 0.06 ± 0.060 a	255.82 ± 136.94# 0.03 ± 0.05*	368.97 ± 72.54 0.12 ± 0.08
FRAP TAC	1472.94 ± 513.83* 1.55 ± 0.76	1637.25 ± 559.25# 1.77 ± 0.64	1343.23 ± 447.80# 1.38 ± 0.81	1012.36 ± 187.76 1.76 ± 0.30

Results are presented as mean ± standard deviation.

*P<0.001, ^#P<0.01, ⁰P<0.05 compared to controls,

^ap < 0.05 compared mild to severe AP.

Conclusion: The iron metabolism is disturbed and the oxidative stress markers are altered during the early phase of acute pancreatitis. The disorders of iron metabolism are associated with the changes of oxidative stress markers.

Disclosure of Interest: None declared

P0096 IMAGING OF PANCREATIC CYSTIC LESIONS WITH CONFOCAL LASER ENDOMICROSCOPY: AN EX VIVO PILOT STUDY

A. Kadayifci¹, M. Atar¹, M. Yang², C. Fernandez-del Castillo³, M. Mino-Kenudson², W. R. Brugge¹

¹Gastroenterology, ²Pathology, ³Surgery, Mass General Hospital, Harvard Medical School, Boston, United States

Contact E-mail Address: kadayifci@hotmail.com

Introduction: The differential diagnosis of pancreatic cystic lesions (PCLs) is an increasingly common clinical challenge. A needle-based confocal laser endomicroscopy probe (nCLE, Cellvisio, Maura Ken Technologies, France) through a 19 G needle has been shown to be helpful for differential diagnosis of PCLs by imaging the cyst wall during endoscopic ultrasound-fine needle aspiration. However, clinical experience is still limited, and better image definition and characterization of the cyst wall from different lesions are needed.

Aims & Methods: The aim of this pilot study was to develop a reference standard in CLE characterization of various types of PCLs. Patients who underwent surgery of a PCL at Mass General Hospital were enrolled to study if they gave their consent. During surgery, intravenous fluorescein (2.5 ml of 10%) was injected just prior to the ligation of blood vessels supplying the pancreas. The injected fluorescein was expected to retain for at least an hour after the injection. The fresh specimens were transected along the long axis to fully expose the luminal surface. A Gastroflex-UHD CLE probe (pCLE) was used manually to acquire images directly from the surface of the cyst wall. The cyst walls were screened longitudinally in 2 millimeter ranges by the tip of the probe and sequences recorded for a total 15 minutes. The entire resected specimen subsequently underwent cross sectional histology. All recorded data were analyzed by two investigators for predefined and original image findings of PCLs.

Results: During the 4-month study period, 10 cases (4 male and 6 female) were recruited into the study. The median age of the patients was 77 (range, 33-88). All patients underwent surgery because of a mucinous cyst with worrisome features or a symptomatic PCL. The median duration between fluorescein injection and confocal imaging was 55 minutes (range, 40-90). Imaging was successful in all patients, and various papillary projections with a vascular core and mucinous epithelial borders were visualized in 8 of the patients. In 2 patients, typical vascular network were visiualized without papillary structures. The conventional pathological examination confirmed 6 cases with Intraductal Papillary Mucinous Neoplasm (IPMN), 2 cases with Mucinous Cystic Neoplasm (MCN) and 2 cases with serous cysts. Pancreatic ductal adenocarcinoma arising in high-grade dysplasia was found in one patient, and high-grade dysplasia in 2 patients. The sensitivity and specificity of ex-vivo confocal imaging to demonstrate papillary structures was 100%.

Conclusion: Pancreatic cyst epithelial wall can be visualized successfully by pCLE in ex vivo surgical specimens. Various papillary projections have been seen in all cases of IPMN and MCN in this examination. The variety of images which have been acquired in this model will be helpful for the definition of similar structures during in vivo examination of pancreatic cysts. To develop a reference standard for definition of IPMN subtypes and for grade of differentiation would be the ultimate aim of this model.

Disclosure of Interest: None declared

P0097 ADIPOSE TISSUE-DERIVED HORMONS AS PROGNOSTIC INDICATORS IN RESECTABLE PANCREATIC CARCINOMA PATIENTS

A. Saray¹, R. Mesihovic¹, N. Vanis¹, B. Gogov¹, A. Mehmedovic¹, A. Valjevac²

¹Institute of Gastroenterology and Hepatology, University Clinical Center Sarajevo, ²Laboratory for Molecular Medicine, Medical Faculty, University of Sarajevo, Sarajevo, Bosnia and Herzegovina

Contact E-mail Address: sarayaida19@gmail.com

Introduction: Prediagnostic plasma adiponectin levels have been inversely associated with an elevated risk of pancreatic cancer (1). We recently demonstrated that in patients with pancreatic cancer (PC) adiponectin levels are inversely correlated with tumor size and tumor grading, identifying a potential link between adipokines and tumor proliferation (2). To date, however, no data on the possible prognostic significance of adipokines in patients with PC have been shown.

Aims & Methods: The aim of the study was to evaluate plasma concentrations of adiponectin and leptin in PC patients and to analyze their possible prognostic value in predicting relapse-free and overall survival. Baseline levels of adiponectin and leptin were determined in 37 consecutive patients with resectable pancreatic adenocarcinoma followed-up from time of surgery for 28 months or until relapse. 37 control subjects were individually matched to case patients by age, sex and BMI. Survival analysis used the Kaplan-Meier curve and the Cox proportional hazards model.

Results: Adiponectin concentrations were lower in PC patients versus control subjects (8.1 vs 10.8. mg/mL, p<0.01) and inversely correlated with tumor size (r= -0.715, p<0.05). The mean leptin levels were not significantly decreased in PC patients (p=0.465). However, the levels of leptin were significantly decreased in cachectic PC patients (N=19) compared with healthy controls (53.9± 25.5 vs 87.0 ± 23.9 ng/ml p < 0.001). Multivariate analysis showed that, beside tumor size, low adiponectin levels were the only independent predictor of recurrence (beta=0.563, p<0.001). High adiponectin levels were associated with an increased overall survival (Cox F test=2.213, p<0.05) and a reduced recurrence rate (Cox F test=2.913, p=0.01) compared to patients with low adiponectin levels.

Conclusion: This study suggests, for the first time, that serum adiponectin levels might represent a prognostic indicator in patients with resectable PC. Our results support the hypothesis linking adipokines levels to malignant tumor growth (3) and suggest that adipokines might exert an adjunctive tool in risk prediction and management of pancreatic adenocarcinoma patients.

Disclosure of Interest: None declared

P0098 FOLFIRINOX IN PANCREATIC CANCER – EXPERIENCE WITH A NOVEL SCHEME OF INDUCTION, MAINTENANCE, TREATMENT PAUSE AND RE-INDUCTION

A. Hann¹, W. Bohle¹, W. G. Zoller¹

¹Department of Internal Medicine and Gastroenterology, Katharinenhospital, Stuttgart, Germany

Contact E-mail Address: a.hann@klinikum-stuttgart.de

Introduction: Chemotherapy regimens for locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) have changed since the introduction of polychemotherapies such as FOLFIRINOX (5-fluoruracil (5FU/LV), oxaliplatin, irinotecan and leucovorin) which confer a significant survival benefit compared to gemcitabine-based monotherapy. Increased toxicity, mainly sensory peripheral neuropathy, limits its use and the number of applied chemotherapy cycles. In analogy to chemotherapy strategies in colon cancer we used a scheme of induction, maintenance, treatment pause and re-induction therapy in locally advanced or metastatic PDAC to alleviate such toxicities and increase the number of applied cycles. In this retrospective study we report our experience with this scheme.

Aims & Methods: We retrospectively identified all patients who received FOLFIRINOX for metastatic or locally advanced PDAC in our center using the induction, maintenance, treatment pause and re-induction scheme until March 2015. Response to therapy and toxicity of the treatment were assessed.

Results: Eleven patients met the inclusion criteria. The median number of cycles of induction therapy including all three active substances or only 5FU/LV combined with oxaliplatin was 6 (range 5-13). All patients had stable disease or partial response and received maintenance therapy consisting of 5FU/LV with a median cycle number of 6 (2-21). Four patients had a treatment pause after maintenance therapy of median 24 weeks (8-42). Re-induction due to progressive disease during treatment pause or maintenance therapy was applied in eight patients using all three active substances or only 5FU/LV combined with oxaliplatin, with a median of 4.5 (2-7) cycles of re-induction therapy. The median time to first progression, death or loss to follow up was 10.8 months (4.1-20.7). The median time to second progression, death or loss to follow up in patients undergoing re-induction chemotherapy was 14.1 months (8.9-29). Peripheral neuropathy was clinically relevant in ten patients after induction therapy. In four of these neuropathy has subsided completely before re-induction therapy.

Conclusion: The maintenance strategy after induction chemotherapy with subsequent re-induction in patients undergoing FOLFIRINOX chemotherapy for advanced PDAC seems to be safe. It might help reduce sensory peripheral neuropathy and potentially leads to a prolonged progression-free survival.

Disclosure of Interest: None declared

P0099 USING A COMBINATION OF MOLECULAR AND CLINICAL FEATURES TO IMPROVE THE CLASSIFICATION OF PANCREATIC CYSTS: A MULTICENTER RETROSPECTIVE STUDY

S. Springer¹, Y. Wang¹, M. Dal Molin¹, D. Masica¹, Y. Jiao¹, I. Kinde¹, A. Blackford¹, S. Raman¹, T. Tomita¹, N. Niknafs¹, C. Douville¹, J. Ptak¹, L. Dobbyn¹, P. Allen², D. Klimstra², M. Schattner², M. Schmidt³, M. Yip-Schneider³, O. Cummings³, R. Brand⁴, H. Zeh⁴, A. Singhi⁴, A. Scarpa⁵, R. Salvia⁶, G. Malleo⁵, G. Zamboni⁵, M. Falconi⁷, J.-Y. Jang⁸, S.-W. Kim⁸, W. Kwon⁸, S.-M. Hong⁹, K.-B. Song⁹, S. C. Kim⁹, N. Swan¹⁰, J. Murphy¹⁰, J. Geoghegan¹⁰, W. Brugge¹¹, C. Fernandez-Del Castillo¹¹, M. Mino-Kenudson¹¹, R. Schulick¹², B. Edil¹², V. Adsay¹³, J. Paulino¹⁴, J. van Hoof¹⁵, S. Yachida¹⁶, S. Nara¹⁶, N. Hiraoka¹⁶, K. Yamao¹⁷, S. Hijioka¹⁷, S. van der Merwe¹⁸, M. Goggins¹, M. Canto¹, N. Ahuja¹, M. Makary¹, M. Weiss¹, K. Hirose¹, J. Cameron¹, M. Pittman¹, J. Eshleman¹, L. Diaz Jr.¹, N. Papadopoulos¹, R. Hruban¹, K. Kinzler¹, B. Vogelstein¹, R. Karchin¹, A. M. Lennon¹

¹Johns Hopkins University, Baltimore, ²Memorial Sloan Kettering Cancer Center, New York, ³Indiana University, Indianapolis, ⁴University of Pittsburgh, Pittsburgh, United States, ⁵University of Verona, Verona, Italy, ⁶University of Verona, Verona, United States, ⁷IRCCS San Raffaele Scientific Institute, Milan, Italy, ⁸Seoul National University, ⁹Asan Medical Center, Seoul, Republic of Korea, ¹⁰St. Vincent's Hospital, Dublin, Ireland, ¹¹Massachusetts General Hospital, Boston, ¹²University of Colorado, Aurora, ¹³Emory University, Atlanta, United States, ¹⁴Hospital Curry Cabral, Lisbon, Portugal, ¹⁵Amsterdam Medical Center, Amsterdam, Netherlands, ¹⁶National Cancer Center Hospital, Tokyo, ¹⁷Aichi Cancer Center, Nagoya, Japan, ¹⁸University Hospitals KU Leuven, Leuven, Belgium

Contact E-mail Address: amlennon@jhmi.edu

Introduction: The clinical management of patients with pancreatic cysts is currently imperfect. The recent identification of a distinct mutational profile in each of the main cyst types (SCAs, SPNs, MCNs and IPMNs) may improve the diagnosis of pancreatic cysts.

Aims & Methods: The aim of this study was to evaluate whether a combination of molecular markers and clinical information could improve the classification and management of pancreatic cysts. A multi-center, retrospective study of patients with resected pancreatic cystic neoplasms was performed. Cyst fluid was analyzed: (i) to identify subtle mutations in genes known to be mutated in pancreatic cysts: BRAF, CDKN2A, CTNNB1, GNAS, KRAS, NRAS, PIK3CA, RNF43, SMAD4, TP53, and VHL; (ii) to identify loss of heterozygozity at the CDKN2A, RNF43, SMAD4, TP53, and VHL tumor suppressor loci; and (iii) to identify aneuploidy. These analyses were performed with highly accurate massively parallel sequencing-based technologies for data acquisition and interpretation. An algorithm was used to select composite molecular markers for classifying cyst type and grade. The accuracy of these composite molecular markers was compared to that of the composite clinical markers, and to a combination of molecular and clinical markers.

Results: We analyzed 12 serous cystadenomas, 10 solid-pseudopapillary neoplasms, 12 mucinous cystic neoplasms, and 96 intraductal papillary mucinous neoplasms. The composite clinical and molecular features classified cyst type with sensitivities of 90% to 100% and specificities of 92% to 98%. The molecular marker panel correctly identified 67 of 74 patients who did not require surgery, thus potentially decreasing the number of unnecessary operations by 91%.

Conclusion: A combination of molecular and clinical markers shows promise for the accurate classification of cystic neoplasms of the pancreas and for the identification of cysts that require surgery.

Disclosure of Interest: S. Springer: None declared, Y. Wang: None declared, M. Dal Molin: None declared, D. Masica: None declared, Y. Jiao: None declared, I. Kinde: None declared, A. Blackford: None declared, S. Raman: None declared, T. Tomita: None declared, N. Niknafs: None declared, C. Douville: None declared, J. Ptak: None declared, L. Dobbyn: None declared, P. Allen: None declared, D. Klimstra: None declared, M. Schattner: None declared, M. Schmidt: None declared, M. Yip-Schneider: None declared, O. Cummings: None declared, R. Brand: None declared, H. Zeh: None declared, A. Singhi: None declared, A. Scarpa: None declared, R. Salvia: None declared, G. Malleo: None declared, G. Zamboni: None declared, M. Falconi: None declared, J.-Y. Jang: None declared, S.-W. Kim: None declared, W. Kwon: None declared, S.-M. Hong: None declared, K.-B. Song: None declared, S. C. Kim: None declared, N. Swan: None declared, J. Murphy: None declared, J. Geoghegan: None declared, W. Brugge: None declared, C. Fernandez-Del Castillo: None declared, M. Mino-Kenudson: None declared, R. Schulick: None declared, B. Edil: None declared, V. Adsay: None declared, J. Paulino: None declared, J. van Hoof: None declared, S. Yachida: None declared, S. Nara: None declared, N. Hiraoka: None declared, K. Yamao: None declared, S. Hijioka: None declared, S. van der Merwe: None declared, M. Goggins Conflict with: inventor royalties, M. Canto: None declared, N. Ahuja: None declared, M. Makary: None declared, M. Weiss: None declared, K. Hirose: None declared, J. Cameron: None declared, M. Pittman: None declared, J. Eshleman: None declared, L. Diaz, Jr. Conflict with: inventor royalties, N. Papadopoulos Conflict with: inventor royalties, R. Hruban Conflict with: inventor royalties, K. Kinzler Conflict with: inventor royalties, B. Vogelstein Conflict with: inventor royalties, R. Karchin: None declared, A. M. Lennon: None declared

P0100 USEFULNESS OF HIGH-INTENSITY FOCUSED ULTRASOUND (HIFU) THERAPY FOR PANCREATIC CANCER

A. Sofuni¹, F. Moriyasu¹, M. Fujita¹, T. Sano¹, T. Tsuchiya¹, S. Tsuji¹, N. Ikeuchi¹, R. Tanaka¹, J. Umeda¹, R. Tonozuka¹, K. Kamada¹, M. Honjo², S. Mukai¹, K. Yamamoto¹, T. Itoi¹

¹Gastroenterology and Hepatology, ²Tokyo Medical University, Tokyo, Japan

Contact E-mail Address: a-sofuni@amy.hi-ho.ne.jp

Introduction: High-intensity focused ultrasound (HIFU) is anticipated as a new advanced therapy for unresectable pancreatic cancer (PC). HIFU therapy with chemotherapy is being promoted as new method to control local advance by ablation of the tumor, and mainly to achieve relief of pain caused by PC.

Aims & Methods: We have evaluated the therapeutic effect of HIFU therapy in locally advanced and metastatic PC. We treated PC patients by HIFU as optional local therapy as well as systemic chemo / chemo-radiotherapy, with whom an agreement was obtained in adequate IC, from the end of 2008 in our hospital. This study was approved by the ethics society of our hospital. HIFU device used is FEP-BY02 (Yuande Bio-Medical Engineering Co.LTD., China). The subjects were 90 PC patients, i.e. 54 cases in stage III, 36 cases in stage IV.

Results: All tumors were visualized by HIFU monitor system. Treatment data in Stage III and IV were as follows: mean tumor size was 33.8 vs 35.7 mm, mean treatment sessions: 2.6 vs 2.4 times, mean total treatment time: 2.2 vs 1.8 hours, mean total number of irradiation: 2595 vs 1962 shots, respectively. There was no significant difference in treatment data between two groups. The effects of HIFU therapy in Stage III and IV were the following; the rate of complete tumor ablation was 87.0 vs 75.0%, the rate of symptom relief effect was 80.0 vs 68.2%, the effectiveness of primary lesion was CR:0, PR:7, SD:38, PD:9 vs CR:0, PR:4, SD:18, PD:14, primary disease control rate (DCR) more than SD was 83.3% vs 61.1%. Comparison of mean survival time (MST) after diagnosis in Stage III and IV was 32.6 vs 16.1 months, respectively (p<0.01, p =0.002). MST after diagnosis in HIFU with chemotherapy and chemotherapy alone (38 patients in our hospital) was 26.7 vs 12.2 months, respectively (p<0.001). Combination therapy of HIFU with chemotherapy was better result than common chemotherapy alone in Stage III.

Conclusion: This study suggested that HIFU therapy has the potential of a new method of combination therapy for PC.

Disclosure of Interest: None declared

P0101 SPECTRAL PATTERN OF DIABETES ASSOCIATED WITH PANCREATIC CANCER

B. Bunganič¹, M. Tatarkovič², L. Šťovíčková², L. Kocourková², Š. Suchánek¹, V. Setnička², M. Zavoral¹

¹Department of Internal Medicine, Military University Hospital, 1st Faculty of Medicine of Charles University Prague, ²Department of Analytical Chemistry, University of Chemistry and Technology, Prague, Czech Republic

Contact E-mail Address: bohus.bunganic@uvn.cz

Introduction: Due to the aggressive nature of pancreatic cancer (PC), the diagnosis of an early stage is essential. In more than 80% of cases, PC is connected with paraneoplastic hyperglycemia called diabetes mellitus associated with PC (DMPC), although only 1% of recent onset diabetics (RODM) have PC.¹ The group of RODM in addition with progressive weight loss or unexplained dyspepsia is a potential screening group for sporadic PC.^1,2 Current diagnostic procedures fall short in distinguishing DMPC from the very frequent type 2 diabetes mellitus (DM2), which represents most of RODM.

Aims & Methods: To specify the differences between DMPC and DM2, we tested a new approach based on combination of spectroscopic methods. The main aim is to determine the sensitivity and specificity of these spectroscopic methods. Plasma samples collected from 23 DMPCs and 24 DM2 patients were analysed by chiroptical spectroscopy, specifically electronic circular dichroism (ECD) and Raman optical activity (ROA), which are inherently sensitive to the 3D structure of chiral molecules.³ To obtain more structural information, the ROA and ECD measurements were supplemented by conventional infrared (IR) and Raman spectroscopies.

Results: The ECD spectra of the DMPCs generally showed not only a lower intensity profile than type 2 diabetics, but also slight changes in the spectral patterns. In the IR spectra, we also observed intensity and spectral pattern variations in the regions corresponding to protein secondary structure. The Raman and ROA spectra showed mainly α-helical peptide/protein conformation with a low content of β-structures. Other observed differences corresponded to aliphatic and saccharide/glycoprotein moieties. The spectra obtained from all four spectral methods were processed by linear discriminant analysis (LDA) showing a clear separation of DMPCs and DM2 patients. The quality of the established statistical model was confirmed by leave-one-out cross-validation where sensitivity and specificity reached 90%.

Conclusion: The results obtained in this pilot study show a high potential of the combination of chiroptical and vibrational spectroscopy as a promising tool in the identification of potential screening group for the diagnosis of early PC.

Acknowledgment: This work was supported by the Ministry of Health of the Czech Republic (projects No. NT 13638 and NT13259-3) and Specific University Research MSMT (No. 20/2015). The authors also thank “Operational Program Prague – Competitiveness “(CZ.2.16/3.1.00/22197) and “National Program of Sustainability “(NPU) MSMT - LO1215; 34807/2013).

Disclosure of Interest: None declared

P0102 OPTIMAL FOLLOW-UP AND LONG-TERM CLINICAL OUTCOME OF PANCREATIC CYSTIC LESIONS

D.-W. Ahn¹, S. H. Lee², D. K. Jang³, K. H. Chung³, B. S. Lee², J. W. Lee², J. H. Son², J. B. Jeong¹, J. K. Ryu², Y.-T. Kim²

¹Internal Medicine, Seoul National University Boramae Medical Center, ²Internal Medicine, ³Seoul National University College of Medicine, Seoul, Republic of Korea

Contact E-mail Address: drdwahn@gmail.com

Introduction: It is generally accepted that cystic lesions in the pancreas (CLPs) 3 cm or less in size and without features suggesting malignancy can be managed conservatively with follow-up. However, the optimal duration and interval of follow-up for CLPs is not yet well established.

Aims & Methods: We have performed the current study to investigate the optimal duration and interval of follow-up for CLPs in clinical practice. Patients with CLPs 3 cm or less in size and without features suggesting malignancy received follow-up with computed tomography at 6, 12, 18, and 24 months and then per 12 months. A retrospective analysis with prospectively collected data was performed.

Results: A total of 205 patients with CLPs detected from 2004 to 2009 (initial mean size, 1.8 ± 0.7 cm) received follow-up during the median period of 56.6 months. Within the first 12 months of follow-up, no patients experienced the growth of cyst and three patients (1.5%) underwent surgery for the presence of symptoms related to CLPs. 11 patients (5.4%) experienced the growth of cyst after 5 years of follow-up. A total of 18 patients underwent surgery during follow-up and four malignant cysts were detected. Overall rate of malignant progression during follow-up was 2.0%. The malignant progression occurred after 48 months and 60 months of follow-up in one and three patients, respectively.

Conclusion: The results of this study provide the evidence of the optimal duration and interval of follow-up for CLPs in clinical practice. Long-term follow-up of more than 5 years should be performed because of the potential for malignant transformation of CLPs. The 12 months interval of follow-up for asymptomatic CLPs might be sufficient in clinical practice.

Disclosure of Interest: None declared

P0103 QUALITY OF LIFE AND CANCER WORRY OF INDIVIDUALS WITH INCREASED RISK FOR FAMILIAL PANCREATIC CANCER

E. J. Shin¹, M. G. Goggins¹, R. D. Schulick², G. M. Petersen³, R. H. Hruban¹, H. Cosby¹, M. Topazian³, S. Syngal⁴, J. J. Farrell⁵, J. Lee⁶, M. Khashab¹, A. M. Lennon¹, C. J. Yeo⁷, M. I. Canto¹

¹Johns Hopkins, Baltimore, ²University of Colorado Anschutz Medical Campus, Aurora, ³Mayo Clinic, Rochester, ⁴7Dana-Farber Cancer Institute, Boston, ⁵8Yale University School of Medicine, New Haven, ⁶MD Anderson Cancer Center, Houston, ⁷Thomas Jefferson University, Philadelphia, United States

Contact E-mail Address: eshin3@jhmi.edu

Introduction: Individuals with a genetic susceptibility for cancer often have a lower quality of life (QoL) than the general population. Little is known about the QoL of individuals with increased risk for familial pancreatic cancer (PC).

Aims & Methods

Aims: 1) To compare the QoL and the cancer worry of asymptomatic adult high-risk individuals (HRI) in a screening program with that of control patients and the general population; 2) To compare the QoL and cancer worry before and after surgical treatment for suspected pancreatic neoplasms detected during screening and surveillance.

Methods: Asymptomatic HRI with a family history of PC or PC genetic syndrome were screened with EUS and MRI within the Cancer of the Pancreas Screening (CAPS) studies from 2000-2011. Participants completed a baseline 36-Item Short-Form Health Survey (SF-36) for QoL analysis and the Cancer Worry Scale (CWS) prior to screening. Cross-sectional comparison of measures was performed with that of concurrently enrolled normal and disease (chronic pancreatitis, pancreatic cyst) controls. Baseline and post-operative scores were compared in surgical patients > 1 year from treatment.

Results: Scores from baseline pre-screening SF-36 and CWS questionnaires of 307 HRI (46% M, mean age 59 years) with 54 controls (42% M, mean age 63 years) were compared. 29 of 32 surgically-treated HRI had follow-up assessments; 13 of these completed both baseline and follow-up questionnaires. Prior to screening, 7 of the 8 QoL domain scores were significantly higher in HRI compared to controls: Physical Functioning (PF; 92 vs 81.9, p=0.005), Role limitation-Physical (RP; 91.2 vs 71.5, p < 0.001), Bodily Pain (BP; 85.3 vs 71.8, p < 0.001), General Health (GH; 71.9 vs 64.5, p < 0.001), Vitality/fatigue (VT; 63.7 vs. 53.4, p < 0.001), Social Functioning (SF; 91 vs 77.2, p < 0.001), and Role limitation–Emotional (RE; 91.3 vs 82.4,p=0.005). Mental health (MH) was comparable (78.7 vs 76.6, p=0.21). HRI had significantly higher mean CWS scores than controls (6.4 vs 5.2, p=0.001). Qol domain scores for the control group were comparable to published normative data for the average U.S. population. There were no statistically significant changes in the QoL parameters before and after surgery: PF (90.4 vs 91.2, p=0.87), RP (80.8 vs 96.2, p=0.09), BP (81.7 vs 87.9, p=0.24), GH (63.5 vs 66.2, p=0.56), VT (59.6 vs 64.2, p=0.54), SF (89.6 vs 88.5, p=0.83), RE (87.2 vs 84.6, p=0.86), and MH (74 vs 76.3, p=0.64). In patients who had pancreatic resection, QoL was high and PC worry was lower after surgery (11.1 pre-op vs 4.8 post-op, p=0.004).

Conclusion: The baseline QoL of asymptomatic HRI is high, and is generally better than that of the controls, despite greater cancer worry. Pancreatic surgery does not negatively impact the QoL of HRI and results in a reduction in cancer worry

Disclosure of Interest: E. Shin: None declared, M. Goggins Conflict with: Epigenomics, Myriad Genetic Laboratories, Inc, R. Schulick: None declared, G. Petersen: None declared, R. Hruban Conflict with: Myriad Genetic Laboratories, Inc., H. Cosby: None declared, M. Topazian: None declared, S. Syngal: None declared, J. Farrell: None declared, J. Lee Lecture fee(s): Boston Scientific Corporation, M. Khashab Consultancy: Boston Scientific Corporation, A. M. Lennon: None declared, C. Yeo: None declared, M. Canto: None declared

P0104 IN-VIVO IDENTIFICATION OF INTRADUCTAL PAPILLARY MUCINOUS NEOPLASIA WITH CONFOCAL ENDOMICROSCOPY

H. Bertani¹, F. Pigò¹, V. G. Mirante¹, A. Caruso¹, M. Manno¹, C. Barbera¹, R. Conigliaro¹

¹Endoscopy Unit, Nuovo Ospedale Civile S.Agostino Estense, Modena, Italy

Contact E-mail Address: helga.bertani@gmail.com

Introduction: Despite several advances in sensitivity and accuracy of diagnostic techniques in abdominal imaging, in the last decades, pancreatic cancer still remains a high-mortality disease with a poor prognosis after 5 years.

Pancreatic cysts are a heterogeneous group of lesions; serous cystadenoma and pseudocyst shows a benign behavior, intraductal papillary mucinous neoplasia (IPMN), mucinous cyst adenoma are considered to be premalignant lesions.

While the management and work up of cystic pancreatic lesions is quite homogeneous between experts, the accuracy of diagnostic techniques is very low. A needle-based confocal laser endomicroscopy probe (nCLE), introduced through an FNA needle, has been presented as able to visualize epithelial layer of a cyst's wall and recently a specific criteria for identification of serous cystadenoma has been identified with nCLE. However nCLE criteria for IPMN, the most common incidental findings in EUS has note been defined yet.

Aims & Methods: The aim of the study was to identify specific imaging criteria of IPMN. After nCLE procedure, all patients underwent aspiration of cystic fluid for CEA, amylase and cytology analysis.

After EUS and nCLE examinations, all findings were compared to cytology, cystic fluid analysis and EUS findings if a surgical specimen was not available and discussed with pathologist in order to recognize typical findings IPMN.

Results: Sixteen patients consequently underwent nCLE during FNA (11 IPMN, 3 Serous cystadenoma, 1 mucinous cystic neoplasm, 1 pseudocyst). nCLE was able to identify images featured finger-like projection suitable with papillary structures in all IPMN (Sens. 100%, Spec 100%, p< 0.02). This finding was not present in serous cystadenoma/pseudocyst/mucinous cystadenoma.

Conclusion: In this pilot study, nCLE was able to identify a criteria common in all IPMN. Multicentric studies on this topic are ongoing.

Disclosure of Interest: None declared

P0105 A COMPARISON OF COVERED AND UNCOVERED METAL STENTS IN PANCREATIC CANCER PATIENTS WITH MALIGNANT BILIARY OBSTRUCTION DURING NEOADJUVANT CHEMORADIOTHERAPY

H. Inoue¹, R. Yamada¹, S. Tano², T. Kitade², M. Katsurahara², Y. Hamada², K. Tanaka², N. Horiki², Y. Takei¹

¹Department of Gastroenterology and Hepatology, ²Department of Endoscoy, Mie University Graduate school of Medicine, Tsu, Japan

Contact E-mail Address: hiro1024@clin.medic.mie-u.ac.jp

Introduction: Increasing numbers of pancreatic cancer patients have been treated with neoadjuvant chemoradiotherapy (NCRT) to improve clinical outcome and survival. Neoadjuvant regimen in our institution would require 5 weeks of chemoradiotherapy, followed by a recovery period of an additional 4 to 6 weeks before surgery. We conducted this study to compare the efficacy and complication rates of covered and uncovered self-expandable metal stents (c-SEMS, u-SEMS) in relieving biliary obstruction in patients undergoing neoadjuvant therapy for pancreatic cancer.

Aims & Methods: We retrospectively analyzed patients who received biliary stent placement between April 2006 and December 2014. Forty-seven patients (34 men/13 women) with locally advanced pancreatic cancer and biliary obstruction had stent placement (24 cases c-SEMS, 23 cases u-SEMS). Endoscopic sphincterotomy (ES) was performed before stent placement.

Results: Stent occlusion occurred in 3 patients (12.5%) in c-SEMS group, 6 patients (26%) in u-SEMS group. Two cases (8.3%) in c-SEMS group and three cases (13%) in u-SEMS group had interruption of NCRT. There was no significant difference between two groups in occlusion rate and interruption of NCRT. There were also no significant differences in stent patency time between two groups (p=0.16). Although tumor ingrowth with recurrent obstruction was more common in the u-SEMS group (21.7%vs 0%), acute cholecystitis (20.8% vs 4.3%) and acute pancreatitis (20.8%vs 8.7%) were more common in the c-SEMS group.

Conclusion: Both c-SEMS and u-SEMS are effective and safe in achieving durable biliary drainage in patients with pancreatic cancer receiving neoadjuvant therapy, despite different patterns of late stent failure.

Disclosure of Interest: None declared

P0106 SURVIVAL PROGNOSTIC FACTORS OF ENTEROPANCREATIC NEUROENDOCRINE TUMORS: A SINGLE-CENTER RETROSPECTIVE ANALYSIS OF 178 CASES

F. Foubert¹, M.-F. Heymann², C. Dumars², H. Senellart³, T. Matysiak-Budnik¹, Y. Touchefeu¹

¹Institut des Maladies de l'Appareil Digestif, ²Anatomopathology Department, ³Institut de Cancérologie de l'Ouest, Nantes, France

Contact E-mail Address: marietillie@hotmail.com

Introduction: Enteropancreatic neuroendocrine tumors (EP-NET) are rare and heterogeneous diseases. The aim of our study was to identify clinical, histopathological and therapeutic factors impacting the survival of patients with EP-NET.

Aims & Methods: All patients with histopathological diagnosis of EP-NET in our university hospital between October 1994 and October 2013 were included. Data were retrospectively collected. When proliferative index (Ki67 and mitotic index) were not available on our database, a prospective review of tumor tissue was performed. Prognostic factors were determined by univariate analysis, survival rates were assessed by Kaplan-Meier method.

Results: One hundred and seventy-eight patients (Male: 53.9%, median age: 57, range: 5-87) were enrolled. There were 112 (62.9%) pancreatic NET and 66 (37.1%) intestinal NET. Sixty-six (37.1%) patients had secretory syndrome. According to the ENETS classification, NET were grade 1, grade 2 and grade 3 in 67 (37.6%), 95 (53.4%) and 9 (5.1%) cases, respectively. Overall survival was significantly longer for pancreatic NET than intestinal NET (192.9 versus 105.2 months, respectively (p=0.0003)). For EP-NET, the identified negative prognostic factors were: age over 75 at diagnosis (HR=5.39; 95% CI: 2.01-14.4), WHO performance status > 1 (HR=9.49; 95% CI: 3.74-24.1), sporadic NET (HR=2.09; 95% CI: 1.06-4.11), presence of distant metastases (HR=2.49; 95% CI: 1.5-4.14), ovarian localization of metastases (HR=6.13; 95% CI: 1.38-27.2) and Ki67 index > 5% (HR=2.21; 95% CI: 1.3-3.76). For pancreatic NET, insulinomas (HR=0.35; 95% CI: 0.14-0.87), primary tumor size < 25mm (HR=0.31; 95% CI: 0.14-0.72) and mitotic index of 0 per 10 fields (HR=0.38; 95% CI: 0.16-0.91) were positive prognostic factors. For intestinal NET, peritoneal localization of metastases (HR=2.65; 95% CI: 1.12-6.28) and emergency surgery for acute complication (HR=2.39; 95% CI: 1.07-5.34) were negative prognostic factors. For patients under 75 years, median survival time was 160 months for grade 2/3 NET while it was superior to 230 months for grade 1 NET (p < 0.05).

Conclusion: Negative prognostic factors such as ovarian or peritoneal metastases should be taken into account for the management of EP-NET. In intestinal NET, surgery should be performed as soon as possible, to avoid the occurrence of severe symptoms leading to emergency surgery. As a cut-off of 5% for the Ki67 index seems to better correlate with survival than a cut off of 2%, the ENETS classification should be reviewed.

Disclosure of Interest: None declared

P0108 PLAC8 OVEREXPRESSION REGULATES CELL GROWTH IN PANCREATIC NEUROENDOCRINE TUMOURS (PNET)

M. Haijat¹, H. Schmidt¹, L. Fiedler¹, T. Gress¹, M. Buchholz¹

¹Klinik für Innere Medizin, SP Gastroenterologie, Philipps-Universität Marburg, Marburg, Germany

Contact E-mail Address: malte.buchholz@staff.uni-marburg.de

Introduction: Plac8 is a small protein with unknown molecular function which depending on the cellular context shows different subcellular localisation and may be involved in a wide variety of physiological and pathophysiological processes. In normal pancreata, Plac8 is expressed neither in the endocrine nor in the exocrine compartment. Here we demonstrate that the protein is strongly upregulated in human pancreatic neuroendocrine tumours (pNETs) and centrally regulates the growth of cultured cells derived from pNETs.

Aims & Methods: Immunohistochemistry, RNAi, cell proliferation and viability assays, Western blots, apoptosis assays

Results: Plac8 is strongly overexpressed in primary human pNET tissues both on the mRNA level, as determined by quantitative RealTime PCR, as well as on the protein level, as determined by Western blot and immunohistochemistry. Moreover, strong Plac8 expression is also retained in cultured cell lines from human and rat pNETs. siRNA-mediated knockdown of Plac8 expression in these cells uniformly resulted in strong inhibition of cell growth, as determined by BrdU incorporation and MTT assays, while apoptosis levels were not influenced. This growth inhibition was associated with upregulation of the cell cycle inhibito p21/CDKN1A as well as downregulation of cyclin D1.

Conclusion: Overexpression of Plac8 protein in pancreatic neuroendocrine tumours is centrally important for the maintenance of the proliferative phenotype of the tumour cells. Further analyses to identify the involved molecular mechanisms and signalling pathways are ongoing.

Disclosure of Interest: None declared

P0109 CLINICAL MANAGEMENT OF SMALL PANCREATIC NEUROENDOCRINE TUMORS (PNETS): RESULTS FROM A 5-YEAR SINGLE-CENTER PROSPECTIVE STUDY

S. Massironi¹, R. E. Rossi¹², A. Zilli¹, D. Conte¹, C. Ciafardini¹, M. Peracchi¹

¹Gastroenterology and Endoscopy Unit, irccs cà granda ospedale maggiore policlinico, ²Postgraduate School of Gastroenterology, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy

Contact E-mail Address: robertaelisa.rossi@gmail.com

Introduction: The most appropriate clinical management for small (≤ 20 mm) non functioning pancreatic neuroendocrine tumors (pNETs) is still a matter of debate and whether all the small and asymptomatic lesions should be routinely resected still has to be defined.

Aims & Methods: Primary endpoints of this prospective study were to evaluate the overall survival (OS) and the progression free survival (PFS) of pNETs, according to their clinical management.

From September 2009 to September 2014, a total of 51 patients had a definite diagnosis of pNETs based on clinical data, imaging (CT, MRI, Ga68-PET), ultrasound endoscopy, histology, and were consecutively enrolled. Among them, 15 patients (M/F= 6/9, median age 65 yrs, range 27-84 yrs) with small pNETs (diameter ≤20 mm) underwent an intensive 3-month follow-up for the first year and biannual thereafter (FU)). TNM stage was I in all but one patient who was at stage IIA. Twenty-one patients (M/F= 7/14, median age 52 yrs, range 27-82 yrs) underwent surgical resection (SR): TNM stage was I, IIA, IIIB and IV in two, nine, one and nine cases, respectively The remaining 15 patients (M/F= 7/8, median age 72 yrs, range 27-87 yrs) received systemic therapy (ST) due to advanced disease or contraindications to surgery; of them five, two and eight were at stage IIA; IIB and IV, respectively.

Results: Median follow up of the entire cohort was 56 months (range 3-70). OS was similar in FU and SR groups, whereas it was significantly worst in ST subset (log-rank test P=0.014, median not reach in each group). Five-year survival rate was 100% in the FU group, 90% in the SR one, and 61% in the ST group (p <0.0001), although these results were largely affected by the different stage at presentation. PFS did not differ in the three groups as disease remained stable in all but one patient in the FU group, whereas six patients (28%) in the SR group showed a pNET recurrence or metastatic spread and finally five (31%) showed disease progression in the ST group.

Conclusion: The “wait and watch“approach appears to be safe in ≤ 20mm, early stage pNETs, although further studies are needed to confirm these results in larger cohorts of patients.

Disclosure of Interest: None declared

P0110 ENDOSCOPIC ULTRASOUND-BASED SURVEILLANCE OF ASYMPTOMATIC PANCREATIC NEUROENDOCRINE TUMORS IN MULTIPLE ENDOCRINE NEOPLASIA TYPE 1 SYNDROME; A RETROSPECTIVE COHORT STUDY TO ASSESS GROWTH RATE

W. Kappelle¹, G. Valk², M. Leenders¹, P. Siersema¹, F. Vleggaar¹

¹Gastroenterology and Hepatology, ²Endocrine Oncology, UMC Utrecht, Utrecht, Netherlands

Contact E-mail Address: w.f.w.kappelle@umcutrecht.nl

Introduction: Endoscopic ultrasound (EUS) is used to identify pancreatic neuroendocrine tumors (PNETs) in multiple endocrine neoplasia type 1 (MEN1) syndrome. The role of surveillance in small (<20 mm), asymptomatic PNETs is unclear, mostly because the natural course of these lesions is largely unknown. Therefore, current advice is to perform EUS at 6-12 months intervals.

Aims & Methods: We assessed the incidence of small, asymptomatic PNETs in MEN1 patients using EUS and calculated the growth rate of PNETs in general, but also of the largest PNET per patient and of incident PNETs identified during follow-up EUS. All linear array EUS procedures in patients with MEN1 syndrome between May 2002 and April 2015 at the UMC Utrecht were identified. Number, size and location of PNETs were recorded. Mean growth rate of PNETs <20 mm identified at initial EUS (prevalent PNETs) and incident PNETs at follow-up was calculated with mixed model linear regression analysis.

Results: Fifty-four patients were identified. After excluding patients that underwent only one EUS-procedure (N=14) and patients without PNETs (N=2), 38 patients were included (13 males [34%]) with a mean age at the first procedure of 41 years (SD 14). Follow-up was 129 patient years (mean 3.4 years [SD 2.3]) and 169 EUS procedures were performed. In total, 225 PNETs were identified with a median size of 5 mm (IQR 4-8). Of these, 124 PNETs (55%) were identified during the initial EUS procedure (prevalent PNETs: median size 6 mm, IQR 4-9) and 101 (45%) during surveillance EUS (incident PNETs: median size 4.3 mm, IQR 3.0-6.0 mm) after a median of 2.4 years (IQR 1.1-3.5). Median size of the largest prevalent PNET (N=33) was 9 mm (IQR 8-13). Mean annual growth rate of all PNETs was 0.10 mm (95% CI 0.02-0.19, P=0.02); PNETs <10 mm did not grow (P=0.50) whilst PNETs ≥10 mm grew 0.75 mm/year (95% CI 0.41-1.09, P < 0.0001). Prevalent PNETs grew 0.21 mm/year (95% CI 0.10-0.32, P=0.0003), while incident PNETs did not grow over time (P=0.21). Annual growth rate of the largest prevalent PNET was 0.28 mm (95% CI 0.06-0.50, P=0.01). Annual incidence of new PNETs was 0.78 PNETs/patient/year (95%CI 0.72-0.86). In three patients (8%), a PNET grew to ≥20 mm during surveillance EUS (number needed to test: 12.7) after 26-30 months. None of the 101 incident PNETs grew beyond 15 mm.

Conclusion: Annual growth rate of small PNETs, especially when <10 mm, is low and the interval between EUS procedures could probably be prolonged without compromising safety. Clinical relevance of new small PNETs found during surveillance appears to be limited because all PNETs ≥20 mm during surveillance EUS were already identified during the initial EUS.

Disclosure of Interest: None declared

P0111 THE PUTATIVE CANCER STEM CELL MARKER DCLK1 IS HIGHLY EXPRESSED IN PANCREATIC NEUROENDOCRINE TUMORS AND INDUCES EPITHELIAL-MESENCHYMAL TRANSITION

Y. Ikezono¹, H. Koga¹, J. Akiba², M. Abe¹, F. Wada¹, T. Nakamura¹, H. Iwamoto¹, T. Sakaue¹, H. Yano², O. Tsuruta¹, T. Torimura¹³

¹Division of Gastroenterology, Department of Medicine, ²Department of Pathology, Kurume University School of Medicine, ³Liver Cancer Research Division, Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan

Contact E-mail Address: ikezono_yuu@kurume-u.ac.jp

Introduction: Accumulating evidence suggests that Doublecortin-like kinase 1 (DCLK1) is a putative marker for intestinal and pancreatic stem cells, including cancer stem cells (CSCs) of these organs^1,2,3. Recently, we have reported that DCLK1 was highly and diffusely expressed in human rectal neuroendocrine tumors⁴. However the function of DCLK1 has not been investigated in detail.

Aims & Methods: The aims of the present study were to assess expression levels of DCLK1 in pancreatic neuroendocrine tumors (PNETs) and to identify critical functions of this molecule in PNET cells that are highly metastatic despite of their relatively slow growing ability. Fifteen patients (8 male, 7 female; mean age, 56) with PNETs were enrolled in this study. Informed consent was obtained from all of the patients. The tumors were surgically resected between 1997 and 2012 in the Kurume University Hospital. Mean diameter of the tumors was 30.2 mm (range, 12-93 mm). Immunohistochemistry (IHC) was employed to assess expression levels of DCLK1. QGP1, a human PNET cell line, was used in this study, and the cells were transfected with dclk1 cDNA to establish the DCLK1-overexpressing (QGP1-DOE) cells. The QGP1-DOE cells were subjected to dclk1 silencing of to confirm acquired cellular characteristics by DCLK1 overexpression. Protein and mRNA expression levels were analyzed by Western blot and real-time PCR (ABI PRISM 7700), respectively.

Results: In IHC, all of the 15 PNET clearly and diffusely expressed DCLK1 in the tumor areas. The protein was expressed in QGP1 cells in both protein and mRNA levels; however, the expressed protein was a short form which lacked doublecortin domains. QGP1-DOE cells robustly expressed full length of DCLK1, showing morphological alteration reminiscent of epithelial-mesenchymal transition (EMT). Indeed, extremely high expression of Slug was found in QGP1-DOE cells compared with control cells at both protein and mRNA levels. Similar upregulation was demonstrated in E2A, Twist, and N-cadherin. The QGP1-DOE cells exhibited increased cellular motility. DCLK1 knockdown restored both cellular morphological change and the expressions of the EMT-associated molecules.

Conclusion: We demonstrated high expression of DCLK1 in human PNET tissues and PNET cells. Enforced expression of DCLK1 induced EMT via upregulating Slug and other EMT regulators. Therefore, it is speculated that inhibition of DCLK1 expression is a novel therapeutic strategy for PNETs.

Disclosure of Interest: None declared

MONDAY, OCTOBER 26, 2015   09:00-17:00

ENDOSCOPY AND IMAGING I – HALL 7__________

P0112 EVALUATION OF THE SPEED AND QUALITY OF GASTRIC ULCER HEALING AFTER ESD USING 2% REBAMIPIDE SOLUTION AS A NOVEL SUBMUCOSAL INJECTION MATERIAL

A. Fujimoto¹, O. Goto¹, T. Maehata¹, Y. Ochiai¹, T. Nishizawa¹, R. Nakamura¹, S. Sagara¹, T. Akimoto¹, M. Shimoda², T. Uraoka¹, N. Yahagi¹

¹Center for Research and Development of Minimally Invasive Treatment, Cancer Center, ²Department of pathology, Keio university, Tokyo, Japan

Contact E-mail Address: ai-fujimoto@a8.keio.jp

Introduction: Rebamipide is a safe and widely used medication for oral administration to patients with gastritis or gastric ulcers. A combination therapy of proton pump inhibitor (PPI) and rebamipide was reported to effectively promote ulcer healing after endoscopic submucosal dissection (ESD).

Aims & Methods: In this preclinical study we developed a novel 2% rebamipide solution as a submucosal injection agent for ESD, used it for ESD experimentally in porcine stomachs, and examined the quality and speed of ulcer healing after the intervention.

Three domestic female pigs of about 30 kg underwent ESD. ESDs of approximately 30 mm in diameter were performed at four sites (anterior and posterior walls of both the upper body and middle body) in the stomach of each of the three pigs. An endoscopist blinded to the test agents performed the ESD with matrix alone at two sites (control group) and with the 2% rebamipide solution at the other two sites (rebamipide group). One pig was sacrificed 1 week later (pig 1) and two pigs were sacrificed 4 weeks later (pigs 2 and 3). In Examination 1 we evaluated the healing speed once a week using endoscopic ulcer staging. In Examination 2 we evaluated the quality of the ulcer scar histopathologically.

Results: Examination 1. We found no significant differences between the groups in the healing stage after resection of the gastric lesions at 1 week. Later, however, the S stage ratios in the rebamipide group and control group were significantly different: 75.0% (3/4) and 50.0% (2/4) respectively at 3 weeks and 100.0% (4/4) and 50.0% (2/4) respectively at 4 weeks. Furthermore, the folds into the centers of the ulcer scars were smoother and more uniform in the rebamipide group than in the control group at 4 weeks after the ESD. Examination 2. The ulcers at 1 week were not observably different between the two groups. At 4 weeks, mucosal healing was conspicuously better in the rebamipide group than in the control group, with a thicker and more uniform mucosal layer.

Conclusion: The use of 2% rebamipide solution as a novel submucosal injection material for ESD promoted the speed and quality of ulcer healing after ESD.

Disclosure of Interest: A. Fujimoto Financial support for research: Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan, O. Goto: None declared, T. Maehata: None declared, Y. Ochiai: None declared, T. Nishizawa: None declared, R. Nakamura: None declared, S. Sagara: None declared, T. Akimoto: None declared, M. Shimoda: None declared, T. Uraoka: None declared, N. Yahagi: None declared

P0113 PREOPERATIVE PULMONARY FUNCTION TESTS ARE USEFUL TO PREDICT ASPIRATION PNEUMONIA AFTER ESD FOR GASTRIC TUMORS

A. Matsumi¹, R. Takenaka¹, Y. Sato¹, K. Takei¹, S. Okanoue¹, E. Yasutomi¹, T. Sunami¹, S. Oka¹, Y. Baba¹, D. Kawai¹, K. Takemoto¹, H. Tsugeno¹, S. Fujiki¹

¹Tsuyama Chuo Hospital, Tsuyama, Japan

Contact E-mail Address: rodyrodyroddick.0616@gmail.com

Introduction: An experienced and skilled ESD operator enables us to perform ESD even for elderly patients with some comorbidities. Such patients whose pulmonary function is often poor may be at risk for postoperative aspiration pneumonia. However, few reports have discussed on the relationship between the pulmonary function and aspiration pneumonia after ESD for gastric tumors.

Aims & Methods: A total of 978 patients with gastric tumors who previously had received pulmonary function tests were treated by ESD between June 2006 and May 2014. ESD was performed under intravenous anesthesia using propofol. Chest radiography and blood chemistry were done on the next day after ESD. Computed tomography was added if aspiration pneumonia was suspected. Aspiration pneumonia was defined when the patients presented with lung consolidation by chest radiography or CT, in addition to respiratory infectious symptoms such as fever and oxygen desaturation. Pulmonary function tests were assessed using a spirometer. The patients were categorized into four groups according to the predicted vital capacity (%VC) and forced expiratory volume in 1 second as a percentage of forced vital capacity (FEV1.0%): normal; restrictive pulmonary dysfunction (%VC < 80%); obstructive (FEV1.0%<70%); and combined (%VC < 80% and FEV1.0%<70%). The factors associated with aspiration pneumonia were retrospectively analyzed using the preoperative parameters.

Results: The study subjects comprised 694 men (71%) and 284 females (29%) with a mean age of 73.6 years. Among the 268 cases (27%) with abnormal pulmonary function, 10 cases (3.7%) developed aspiration pneumonia. On the other hand, 7 cases (1.0%) with normal pulmonary function developed pneumonia. There was a significant correlation between pulmonary function and aspiration pneumonia (p=0.003). The pulmonary function cases were stratified into subgroups, 2.5% of cases with restrictive pulmonary dysfunstion developed pneumonia, 5.5% with obstructive, and 7.9% with combined. Among the other preoperative parameters, serum albumin, pretreatment with glucagon, presence of antiplatelet agent, presence of cerebral vascular disease were significant factors by a univariate analysis. By multivariate analysis, pulmonary function and presence of cerebral vascular disease were identified as significant independent risk factors associated with aspiration pneumonia. The odds ratio for pulmonary function and cerebral vascular disease were 3.2 and 5.1, respectively.

Conclusion: Preoperative pulmonary function tests may be useful markers to evaluate the risk for aspiration pneumonia after ESD for gastric tumors.

Disclosure of Interest: None declared

P0114 USEFULNESS OF BLUE LASER IMAGING (BLI) FOR DETECTION OF SUPERFICIAL ESOPHAGEAL SQUAMOUS CELL CARCINOMA

A. Tomie¹, N. Yagi¹, Y. Nakahata¹, H. Kitae¹, Y. Oshima¹, A. Obora¹, T. Kojima¹, R. Kimura², O. Dohi³, K. Kamada³, Y. Naito³

¹Gastroenterology, Murakami Memorial Hospital,Asahi University, Gifu, ²Medical Oncology, Fukushima Medical University, Fukushima, ³Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan

Contact E-mail Address: t.rakira@gmail.com

Introduction: In recent years, image-enhanced endoscopy such as NBI is widely performed for detection and diagnosis of superficial ESCC. Especially, NBI has established the usefulness in detection and diagnosis of superficial ESCC. Blue LASER Imaging (BLI) is a novel image-enhanced endoscopy with two different lasers that enable us to allow narrow-band light observation. BLI-bright is a brighter BLI mode, and useful for endoscopic observation in a distant view.

Aims & Methods: The aim of this study is to evaluate the endoscopic recognition of ESCC using by four different methods (OLYMPUS white light: OWL, FUJIFILM white light: FWL, NBI, and BLI-bright). We retrospectively analyzed 25 superficial ESCCs that were examined using among OWL, FWL, NBI, and BLI-bright at Kyoto Prefectural University of Medicine (KPUM) from March 2012 to December 2014. A typical ESCC was observed as a reddish area (RA) by using OWL and FWL, or as a brownish area (BA) by using NBI and BLI-bright in a distant view. Subjective evaluation was investigated as a ranking score (RS) by three endoscopists who ranked the each image on the basis of the ease of detection of cancer area (very clear: 3 scores/ clear: 2 scores/ unclear: 1 score). As objective evaluation, we calculated the Color Difference Scores (CDS) of pixel values based on L*a*b* color spaces between each cancer and noncancerous area.

Results: There are no difference between the mean RS of OWL and FWL. The mean RS of NBI was significantly higher than OWL (p<0.01) and that of BLI-bright was significantly higher than FWL (p<0.01). Moreover, the mean RS of BLI-Bright was significantly the higher than NBI (p<0.01). Furthermore, in the objective evaluation, the mean CDS of BLI-bright was significantly the highest than that of OWL (p<0.05), FWL (p<0.01) and NBI (p<0.01). Therefore, BLI-bright images was significantly higher than that obtained from the other methods both RS and CDS.

Conclusion: The recognition of cancer areas using BLI-bright was the most clear than using the other methods (OWL, FWL, and NBI) both subjectively and objectively. BLI bright may be a valuable tool for identifying superficial ESCCs during screening endoscopy.

Disclosure of Interest: None declared

P0115 LONG-TERM OUTCOME AFTER BIODEGRADABLE STENT (BDS) PLACEMENT FOR THE TREATMENT OF REFRACTORY BENIGN ESOPHAGEAL STRICTURES

A. Repici¹, E. Ferrara¹, A. Murino¹, S. Carrara¹, C. Hassan², M. Jovani¹, C. Ciscato¹, A. Loriga¹, S. Sferrazza¹, A. Anderloni¹

¹Digestive Endoscopy Unit. Division of Gastroenterology, Humanitas Research Hospital, Rozzano, Milano, ²Digestive Endoscopy Unit, Catholic University, Rome, Italy

Contact E-mail Address: alessandro.repici@humanitas.it

Introduction: Metal stent placement has been proposed as potential treatment for refractory benign esophageal strictures. Biodegradable stents (BDS) have been used to overcome the traditional shortcomings of metal stents for benign indications. However BDS were evaluated only in small cohort studies with a short follow-up.

Aims & Methods: Aim of this study is to report long-term outcome and safety of a large group of patients treated with BDS over 6 years. Prospectively maintained database has been used to collect data on consecutive patients with refractory benign esophageal strictures (according to Kochman criteria) treated at a single tertiary level centers using a BDS since 2008. BDS have been placed under fluoroscopy; endoscopic and radiologic follow-up was planned at 3 and 6 months followed by a phone interview or outpatient appointment. Technical success was defined as uneventful placement of the BDS at the level of the stricture. Clinical success was defined as the absence of dysphagia for at least 12 months after BDS placement. Recurrent dysphagia due to stricture formation was defined as any recurrent stricture that could not easily be passed by a standard endoscope (9.8mm) together with symptoms of dysphagia for solid food (grade ≥2).

Results: 42 patients (28M, mean age 53.2 y) received a BDS. In 26 patients a small size (18-23 mm) BDS was used while a larger BDS (23-25 mm) was placed in the reaming. Stricture etiology was post-surgery in 12 (28.5%), post-caustic ingestion in 20 (47%), post-radiotherapy in 8 (19%) and idiopathic in 2 (4.7%). Mean number of dilation before BDS was 12.6 (range 8-17) and 17 patients were previously treated with fully covered metal stent. BDS was successfully placed in all patients. Early complications occurred in 11 patients (26%) and were mainly related to thoracic pain requiring prolonged medical therapy in 10 and stent migration in 1 patient just two weeks placement. Late complications were observed in 3 patients (2 perforation occurred respectively 4 and 6 weeks after placement and 1 bleeding requiring hospitalization 8 weeks after placement). The overall complication rate was 33%. One patient died after surgery, required because of perforation. The second perforation was managed uneventfully placing a fully covered stent. Mean follow-up was 38.3 months (range 17-68). Long-term relief of dysphagia was obtained in 11 out of 42 treated patients (26%). The median dysphagia-free period was 293 days (range 35-1688). Long-term relief of dysphagia was significantly associated to post-surgery stricture (p=0.001). There was no difference in terms of BDS diameter between patients with or without complications.

Conclusion: BDS in patients with esophageal refractory strictures was associated with 26% success rate and 33% complication rate, leading to surgical intervention in 2 cases and death in 1 case. Caution is recommended when BDS is considered for treatment of benign refractory strictures related to post-caustic ingestion or post-radiotherapy.

Disclosure of Interest: None declared

P0116 UPPER GASTROINTESTINAL CANCER MISSES: COULD WE DO BETTER?

A. H. Gahanbani Ardakani¹, S. Mann¹

¹Gastroenterology, Barnet General Hospital, London, United Kingdom

Contact E-mail Address: amir.ardakani@nhs.net

Introduction: Endoscopy is the gold standard investigation for the diagnosis of gastro-oesophageal cancer. As occurs with lower GI malignancy, cancers can be missed at endoscopy, but this may not be appreciated by the endoscopist, nor is audit of gastroscopy as well established as that for colonoscopy. Studies have suggested that endoscopy technique may account for the majority of misses. In general, a cancer detected within 3 years following an endoscopy is considered to be a ‘potential miss’ and if detected within 1 year after an endoscopy, that is likely to be a ‘definite miss’. This is based on the premise that early oesophageal cancers have a long natural history (1,2).

Aims & Methods: The aim of this study was to establish the proportion of missed upper GI cancers at our institution. We conducted a retrospective, case study of patients diagnosed with oesophageal and gastric cancers between January 2011 and January 2015 from our hospital cancer registry. Information regarding any gastroscopies done within 3-36 months of cancer diagnosis was obtained for each patient using our electronic endoscopy reporting tool.

Results: There were 305 new cases (Male =207; 68%; mean age 73.8 yrs; range 26-100 yrs) of upper GI cancer, of whom 23 (7.5%) had undergone a gastroscopy within 3–36 months of the diagnosis. Only 2 patients had undergone an endoscopy procedure in the 3–12 months prior to diagnosis. Alarm symptoms were present in 11 patients (48%; information available in 20 patients) at the time of the index ‘miss’ endoscopy.

Conclusion: Oesophago-gastric cancers appear to have been missed at endoscopy in 7.5% of patients in our unit. This value parallels outcomes reported elsewhere (1,2). Given the poor prognosis associated with upper GI malignancy, this study reminds us to be vigilant when examining the mucosa, particularly at the cardia, which is most vulnerable with regards to missing a cancer. The endoscopist should also have a low threshold for suspicion in patients presenting with alarm symptoms. Although there are many established performance indicators for colonoscopy, endoscopists are less familiar with gastroscopy measures of quality. We believe that addressing gastroscopy technique will have an impact on early detection of upper GI cancers and improve outcomes for these patients.

Disclosure of Interest: None declared

P0117 PREDICTORS OF OUTCOMES AND LEARNING CURVE FOLLOWING PER ORAL ENDOSCOPIC MYOTOMY FOR ACHALASIA CARDIA

A. Maydeo¹, N. Joshi¹, S. Bhandari¹, V. Dhir¹

¹Baldota Institute of Digestive Sciences, Mumbai, India

Contact E-mail Address: amitmaydeo@gmail.com

Introduction: Per Oral Endoscopic Myotomy (POEM) is an effective treatment for achalasia cardia. There are no studies evaluating predictors of POEM outcome and the impact of learning curve. This single-center, retrospective study aimed at evaluation of predictors of POEM outcomes and assess the impact of learning curve.

Aims & Methods: 268 patients with achalasia cardia were subjected to POEM. POEM was done by posterior approach in first 208 patients, and anterior approach in the next 60 patients. Hybrid knife was used in 200 and triangular tip knife in 68 patients. Primary outcome measure was treatment success defined by Eckardt’s score ≤3. Secondary measures were adverse events. Multivariate analysis was done for factors affecting outcome and learning curve determination was done.

Results: Technical success was achieved in all patients. There were 9(3.35%) treatment failures. Six failures occurred in the first 40 patients, while 3 occurred in the next 228 patients (15% vs. 1.3%, p=0.0005). There were 12 adverse events (AE) in the first 40 patients (30%), and 26 (11.4%) in the next 228 patients (p=0.005). On multivariate analysis, the factors adversely affecting treatment success were male gender (p = 0.017) and prolonged operative time (p= 0.030). Prolonged operative time (p = 0.006) and type of achalasia (p=0.034) were found to be independent predictors of AE.

Conclusion: Male gender, type of achalasia and prolonged operative time are important predictors of adverse POEM outcome. The treatment success improves, and the rate of adverse events declines significantly after first 40 procedures

Disclosure of Interest: None declared

P0118 “DO WE ALWAYS HAVE WHAT WE FEEL?” - PREDICTIVE FACTORS FOR ESOPHAGEAL FOREIGN BODIES PRESENCE IN URGENT ESOPHAGOSCOPY

A. R. Alves¹, S. Giestas¹, P. Figueiredo¹, C. Sofia¹

¹Gastroenterology Department, Coimbra Hospital and University Centre, Coimbra, Portugal

Contact E-mail Address: alvess.anarita@gmail.com

Introduction: Urgent upper digestive endoscopy is frequently required in cases of suspected esophageal foreign bodies (EFD). Persistent esophageal symptoms following foreign bodies ingestion should be evaluated by endoscopy; however, absence of EFB requiring endoscopic removal when esophagoscopy is performed is frequently observed.

Aims & Methods

Aims: Identify predictive factors for EFB presence in urgent esophagoscopy.

Patients and Methods: Retrospective case-control study. All consecutive esophagoscopies performed due to persistent esophageal symptoms after involuntary foreign bodies ingestion were analyzed, during an 18 months period. Demographic and relevant clinical data from patients with presence or absence of EFB when esophagoscopy was performed were compared. Statistical analysis included Fisher, Qui² and t tests for univariate analysis and logistic regression for multivariate analysis.

Results: One-hundred and sixty-one patients were submitted to urgent esophagoscopy due to clinical suspicion of EFB impaction (mean age 60.5 ± 18.2 years, 61.2% female). Impaction of EFB was confirmed in 41.6% of patients. Most frequent foreign bodies were: meat bones 39.8%, fish bones 39.8%, pits 3.7%, dental prosthesis 3.1%, blister pills 2.4% and sharp metal objects 1.2%. Patients with EFB were significantly older than the patients without EFB (60.5 ± 18.2 vs. 49.7 ± 18.7 years; p < 0.001) and recurred earlier to the urgency (10.7 ± 15.1 vs. 21.0 ± 26.5 hours; p=0.003). Relevant underlying diseases, namely neurological, psychiatric or otorhinolaryngological (ORL), were more prevalent in patients with EFB (17.9% vs. 2.1%; p < 0.001). Regarding specific pathology type, a higher prevalence of psychiatric (9.0% vs. 2.1%; p=0.049) and ORL conditions (6.0% vs. 0.0%; p=0.016) was found in patients with EFB. No differences were found between patients with or without EFB concerning gender, day of the week of ingestion, type of foreign body type ingested or underlying neurological problems. Multivariate analyses identified the following predictive factors for EFB presence in esophagoscopy: older age, earlier recurrence to urgency and underlying psychiatric or ORL diseases (OR=7.0; IC95%:1.4-35.0).

Conclusion: In cases of persistent esophageal symptoms after involuntary foreign bodies ingestion, less than half of patients had an effective EFB. Older age, earlier recurrence to urgency and psychiatric or ORL problems were associated with EFB presence when esophagoscopy was performed.

Disclosure of Interest: None declared

P0119 ROUTINE PREOPERATIVE UPPER ENDOSCOPY IN PATIENTS UNDERGOING BARIATRIC SURGERY

A. Vaz¹, M. Eusebio¹, A. Antunes¹, T. Gago¹, P. Queirós², M. Sanchez³, T. Sanai³, J. Teixeira³, R. Ornelas¹, H. Guerreiro¹

¹Gastroenterology, Centro Hospitalar do Algarve, Faro, ²Gastroenterology, Centro Hospitalar do Algarve, Portimão, ³Surgery, Centro Hospitalar do Algarve, Faro, Portugal

Contact E-mail Address: anam_vaz@hotmail.com

Introduction: The difficulty of endoscopic evaluation of the remaining stomach after bariatric surgery is a fact that concerns a great number of doctors. However, the performance of a routine preoperative upper endoscopy (EGD) in every patient is not consensual, because these are mostly young and healthy patients with a low risk of malignancy.

Aims & Methods: Our aim was to evaluate the findings and relevance of preoperative EGD. We performed a retrospective study including patients who had undergone EGD before bariatric surgery between January 2012 and December 2014

Results: A total of 200 patients were studied; 90% were females, with a mean age of 44.2 ± 11.2 years. The mean weight and body mass index were 109.6 ± 18.2Kg and 42.2 ± 4.9 Kg/m², respectively. Sixty-nine patients (34.5%) reported symptoms (heartburn/regurgitation or epigastric pain) before the EGD. There were endoscopic findings in 47% of the patients, the most common being hiatal hernia (19.5%), gastritis (19.5%), esophagitis (10%), gastric polips (3.5%) and duodenitis (3%). Gastric biopsies were performed in 186 patients with positive findings in 129 (69.4%) of them: acute and/or chronic gastritis in 100% and intestinal metaplasia in 3.8%. The presence of symptoms didn’t correlate significantly with the presence of endoscopic or histologic findings.

One hundred and ninety-one proximal gastric bypasses (95.5%) and 9 sleeve gastrectomies were performed. In 4 patients, a hiatal hernia repair was done concomitantly. Postoperative complications occurred in 12 (6%) patients, the most common being anastomotic stricture, without any significant correlation with endoscopic or histologic findings.

Conclusion: Endoscopic and histologic findings were common in preoperative EGD but they did not conditioned significant changings in the planned surgical procedure nor did they correlated with postoperative complications in our study. However, in the absence of correlation between symptoms and endoscopic findings and being EGD an accessible exam, it seems reasonable to perform it in all patients before bariatric surgery.

Disclosure of Interest: None declared

P0120 GASTRIC PRECANCEROUS CONDITIONS AND LESIONS IN LYNCH SYNDROME PATIENTS

Â. Rodrigues¹, R. Marcos-Pinto¹, D. Libânio², M. Dinis-Ribeiro², I. Pedroto¹

¹Centro Hospitalar do Porto - Hospital Santo António, ²Instituto Português de Oncologia, Porto, Portugal

Contact E-mail Address: angelamaria.cr@gmail.com

Introduction: Gastric cancer is the second most frequent extracolonic neoplasm in Lynch syndrome (LS) patients. The majority of them are intestinal adenocarcinomas, consequent to the progression of precancerous conditions and lesions. The main groups recommend performing an upper endoscopy, but with low level of evidence and depending on local context. The objective was to evaluate the prevalence of precancerous conditions and lesions (risk phenotype) in LS patients.

Aims & Methods: Case-control study with evaluation of gastric phenotype (endoscopy with biopsy) and Helicobacter pylori (Hp) infection status (histology and serology).

Results

Cases: 36 patients, from 17 families, MSH2 mutations in 58%, MLH1 in 28% and MSH6 in 14%, family history of gastric cancer in 8 families.

Controls: 100 dyspeptic patients. Around 50% males (41% in controls), average age of 53.25 ± 12.62 (42.56 ± 12.34 in controls). LS patients had a higher prevalence of atrophy of the antrum (33.3% versus 19%, OR 2.13 95% CI 0.91-5.01), intestinal metaplasia of the antrum (16.7% versus 13%, OR 1.34 95% CI 0.47-3.83), extensive atrophy (8.3% versus 4%, OR 2.18 95% CI 0.46-10.26) and extensive intestinal metaplasia (2.8% versus 1%, OR 2.82 95% CI 0.17-46.44) than the controls. Patients with LS had a higher prevalence of Hp infection (78.8% versus 59%, p <0.05).

Conclusion: Our results suggest that there is a higher tendency to precancerous gastric conditions in LS patients, although with no statistical significance, which can be due to the small sample size. Nevertheless, LS patients were older and had a higher prevalence of Hp infection, which can have impact on results. Larger studies are important to define if LS is indeed associated with a risk gastric phenotype and if a systematic and periodic endoscopic surveillance should be recommended.

Disclosure of Interest: None declared

P0121 ENDOSCOPIC FULL-THICKNESS RESECTION IN THE DUODENUM - A CASE SERIES

A. Schmidt¹, B. Meier¹, K. Caca¹

¹Department of Gastroenterology, Klinikum Ludwigsburg, Ludwigsburg, Germany

Contact E-mail Address: arthur.schmidt@gmx.de

Introduction: Endoscopic resection of duodenal non-lifting adenomas and subepithelial tumors is challenging and harbors a significant risk of complications. We report on a novel technique for duodenal endoscopic full thickness resection (EFTR) using an over-the-scope device.

Aims & Methods: Aim of this study was to demonstrate feasibility of EFTR in the duodenum using a novel full-thickness resection device (FTRD, Ovesco Endoscopy, Tuebingen, Germany). Data of 4 consecutive patients who underwent duodenal EFTR was analysed retrospectively. Main outcome measures were technical success, R0 resection, histologically confirmed full thickness resection, adverse events.

Results: Four patients (median age: 60 y) with non-lifting adenomas (2 patients) or subepithelial tumors (2 patients) underwent EFTR in the duodenum. All lesions could be resected successfully. Mean procedure time was 67.5 min (range 50-85). Minor bleeding was observend in 2 cases; blood transfusions were not required. There was no immediate or delayed perforation. Mean diameter of the resection specimen was 28.3 mm (range 22-40). Histology confirmed complete (R0) full thickness resection in 3 of 4 cases. Endoscopic follow-up after 2 months could so far be obtained in 2 patients. In both cases, the OTSC was still in place in could be removed without complications, recurrencies were not observed.

Conclusion: EFTR in the duodenum with the FTRD is a promising technique which has the potential to spare surgical resections. Modifications of the device should be made to facilitate peroral introducability. Prospective studies are needed to further evaluate efficacy and safety for duodenal resections.

Disclosure of Interest: None declared

P0122 CAUSTIC INGESTION, IS ENDOSCOPY ALWAYS REQUIRED? – CLINICAL AND LABORATORY MODEL FOR PREDICTING GASTROINTESTINAL LESIONS

A. G. Antunes¹, C. Teixeira², M. Eusébio¹, S. Ribeiro², A. Alves², B. Peixe¹, P. Oliveira², H. Guerreiro¹

¹Gastroenterology department, Centro Hospitalar do Algarve, Faro, ²Gastroenterology department, Centro Hospitalar de Setúbal, Setúbal, Portugal

Contact E-mail Address: sergiogiao@hotmail.com

Introduction: The ingestion of caustic substances is one of the major areas of Gastroenterology emergency, and the endoscopic evaluation is the gold standard for assessing the grade of lesions and to define the prognosis. However, in addition to being contraindicated in severe situations, it is not risk-free and its usefulness is debatable in cases of asymptomatic patients without oropharyngeal lesions.

Aims & Methods: (1) To identify clinical and laboratory factors for predicting gastrointestinal caustic injury; (2) creation of a clinical and laboratory model that could identify patients with high-grade gastrointestinal lesions (HGGL) and low-grade gastrointestinal lesions (LGGL), without need of performing an endoscopy.

Multicentric retrospective study, that reviewed all the patients who ingested caustic and were admitted to our centers over a period of 10 years. For defining the grade of lesions, we used Zargar score system (HGGL ≥ 2B; LGGL ≤2A). We identified clinical and laboratory variables that were statistically significant associated with HGG and we calculated the correlation coefficient.

Results: We identified 133 patients, of whom 65 had a HGGL (Esophagus: 50 patients; Stomach: 43 patients).

When comparing patients with and without HGGL, we identified statistically significant differences for the variables average value of leukocytes (15.3 versus 9600 x10⁹/L; p = 0.000) and CRP (73 versus 25 mg/L; p = 0.000). The variables leukocytes (rs = 0.497; p = 0.000), CRP (r = 0.485; p = 0.000) and the number of symptoms (rs = 0.667; p = 0.000) showed a significant moderate correlation to HGGL. In univariate analysis, ingestion of acid (X² = 6.881; p=0.009), ulcers in the oropharynx (X² = 18.304; p = 0.000) and hemodynamic instability (X² = 19.027; p = 0.000) were also associated with HGGL.

There was no statistical association between HGGL and the variables gender, intentional ingestion, age, previous attempt, psychiatric disease and dependence of toxic substances.

The factors with the strongest relationship to HGGL (leukocytes count; CRP; symptoms; ulcers in the oropharynx and hemodinamic instability) were used to develop an objectively weighted multivariate prognostic score ranging from 0 to 14 points, with a good prognostic discrimination (area under the receiver operating characteristic curve = 0.901). The ROC curve analysis suggests for identification of HGGL, the optimal cut-off of 10 points, with a specificity of 97% and sensitivity of 64%; and for LGGL the cut-off of 5 points, with a specificity of 94% and a sensitivity of 66%.

Conclusion: Our results confirm the model as a good test (AUC = 0.901), but in need of prospective validation, preferably in international multicentric studies.

Disclosure of Interest: None declared

P0123 DUODENAL ENDOSCOPIC SUBMUCOSAL DISSECTION; SINGLE CENTER EXPERIENCE IN TURKEY

F. Aslan¹, Z. Akpınar¹, M. Arabul¹, H. Çamyar¹, M. Kartal¹, M. Camcı¹, B. Ünsal¹

¹Gastroenterology, Katip Celebi University Ataturk Training and Research Hospital, Izmir, Turkey

Contact E-mail Address: drfatihaslan@hotmail.com

Introduction: Endoscopic Submucosal Dissection (ESD) is an endoscopic treatment modality providing en-block and complete resection of mucosal and submucosal lesions. Duodenal ESD is technically more difficult than gastric and colorectal ESD with longer procedure duration and higher complication risk. Here we present our experience with duodenal ESD.

Aims & Methods: A total of 345 ESD procedures of the esophagus, stomach, colorectum and duodenum had been performed between April 2012 and April 2015 the data of which had been recorded prospectively. During this study the records were searched retrospectively and the results of 8 duodenal ESD were analyzed.

Results: Duodenal ESD had been performed only after performing more than 200 ESD of stomach, esophagus and colorectum. There were 8 patients with duodenal ESD, in 5 patients the lesion was in the duodenal bulb and in 3 patients the lesion was in the second part of the duodenum. The median age of patients was 59.5 years (38-72y), median length of resected tissue was 33.5 mm (14-73), median length of lesion was 16.5 mm (9-67) and median procedure duration was 31.5 min. (16-345).

All the lesions were removed en-block. On histopathological examination both lateral and vertical margins were clear in all patients. During the procedure perforation occurred in patient which was successfully treated medically and with endoscopic clipping. No recurrence was seen during endoscopic follow-up and complete resection was achieved in all patients (Table).

Abstract number: P0123

No	Age/gender	Localization	Duration of procedure (minutes)	Size of lesion (mm)	Size of tissue (mm)	En-Block Resection	Complication	Histopathology	Complete resection
1	65,M	Duodenal bulb	33	13 x 11	21 x 15	Yes	-	Neuroendocrine tumor	Yes
2	72,M	Duodenal bulb	16	11 x 8	20 x 17	Yes	-	Neuroendocrine tumor	Yes
3	59,M	2nd part of duodenum	19	15 x 13	20 x 20	Yes	-	Tubular Adenoma (High Grade Dysplasia)	Yes
4	44,F	Duodenal bulb	29	10 x 8	14 x 12	Yes		Neuroendocrine tumor	Yes
5	38,F	2nd part of duodenum	126	28 x 19	35 x 25	Yes	Perforation	Tubular Adenoma (High Grade Dysplasia)	Yes
6	60,F	2nd part of duodenum	345	67 x 38	73 x 48	Yes	-	Intramucosal carcinoma	Yes
7	72,M	Duodenal bulb	54	12 x 11	21 x 15	Yes	-	Neuroendocrine tumor	Yes
8	66,F	Duodenal bulb	67	16 x 14	32 x 24	Yes	-	Neuroendocrine tumor	Yes

Conclusion: Although duodenum is a difficult localization for endoscopic interventions and duodenal ESD bears higher complication risks because of thin wall, as the guidelines suggest, we believe that after experiencing in stomach and rectal ESD, duodenal ESD can also be performed successfully when needed.

Disclosure of Interest: None declared

P0124 GRADING ATROPHIC GASTRITIS BY A NEW QUANTITATIVE METHOD USING CONFOCAL LASER ENDOMICROSCOPY PROBE (P-CLE): FIRST RESULTS OF A PROSPECTIVE COHORT STUDY

C. Robles-Medranda¹, M. Puga-Tejada¹, J. Ospina¹, M. Soria¹, G. Bravo¹, R. Del Valle¹, H. Pitanga Lukashok¹

¹Endoscopy, Instituto Ecuatoriano De Enfermedades Digestivas, University Hospital Omni, Espiritu Santo University, Guayaquil, Ecuador

Contact E-mail Address: carlosoakm@yahoo.es

Introduction: Atrophic gastritis (AG) is a chronic disease, associated to gastric adenocarcinoma moreover if severe AG is present. Sydney system classifies AG as mild, moderate and severe, but with moderate interobserver agreement, as this system is based on a visual analogic scale (qualitative analysis). Confocal endomicroscopy showed an accuracy of 98% for diagnosis of gastric diseases, but when grading AG still remains a qualitative measure. Recently, new software called “Cellvizio® Viewer” (CV) permits to measure in micrometers (µm) the structures observed after p-CLE studies.

Aims & Methods: Based on the hypothesis that AG severity is correlated with crypts size diminution, the aim of this study is to determine a quantitative way to classify the severity of AG measuring the crypt area and inter-crypt spaces in patients with AG. After approval by the ethics committee 200 consecutive patients that underwent to upper endoscopy (UE) evaluation were included in this prospective study. Inclusion criteria: dyspepsia >12 months, age ≥18, no history of UE evaluation, AG at histopathology, acceptance to participate. Exclusion criteria: use of PPI´s, antibiotics or NSAID´s, gastric cancer, gastric surgery, pregnancy, contraindication to fluorescein. During UE 5 biopsy sites were performed in accordance to Sydney system first using p-CLE and then by biopsy forceps from the same site. At p-CLE normal crypt was defined by using the classification of Wang et al (1). After histopathology confirm AG, crypts were analyzed using the CV software measuring the crypts diameters, to determine the area by elliptic area formula (A = π.d₁.d₂) and measuring inter-crypt space. That space was defined as the mean of each measured distance between the studied crypt and its adjacent. The cutoff value between mild, moderate and severe AG, crypts area was classified across tertiles, expressing its distribution using a box-spot graphic. For relationship between crypt area (CA) and inter-crypt space, quadratic polynomial regression was used. Data was processed using IBM® SPSS® Statistics.

Results: 30 patients were identified to have AG, 16 females (55%) with a mean age of 47.82 ± 18.3 and 146 crypts were analyzed. Histopathology showed AG: absent in 10 (38.5%), mild 8 (30.8%), moderate 6 (23.1%) and severe 2 (7.7%) of cases. At p-CLE the mean CA was 4697 (848 – 14794), and average of mean inter-crypt distance was 33.76 (0.00 – 87.45). Minimum normal CA was 10000 µm². Classifying AG crypts was established as follow: mild atrophic CA (µm2) range: 5000 and <10000, moderate AG CA: 3000 and <5000. Severe AG CA was <3000. Quadratic polynomial regression established a statistically significant relationship between CA and inter-crypt space

Conclusion: Using p-CLE criteria, severity of AG could be defined through crypt area and inter-crypt space with values of <3000µm² and 40µm respectively.

Disclosure of Interest: None declared

P0125 CLINICAL IMPACT OF CONFOCAL LASER ENDOMICROSCOPY PROBE (P – CLE) IN THE MANAGEMENT OF GASTROINTESTINAL NEOPLASIC AND NON-NEOPLASIC LESION

C. Robles-Medranda¹, J. Ospina¹, M. Puga-Tejada¹, M. Soria¹, G. Bravo¹, C. Robles-Jara¹, H. Pitanga Lukashok¹

¹Endoscopy, Instituto Ecuatoriano De Enfermedades Digestivas, University Hospital Omni, Espiritu Santo University, Guayaquil, Ecuador

Contact E-mail Address: carlosoakm@yahoo.es

Introduction: It has been demonstrated that endoscopic and histopathology findings don’t have good correlation, leading sometimes to diagnostic and therapeutic doubts. Confocal laser endomicroscopy probe (p-CLE) is a new technology which permits in-vivo cellular view of gastrointestinal mucosa. It includes esophagus, stomach, small intestine, colon, biliary tract and pancreas. Studies showed a diagnostic accuracy above 90% for neoplastic (N) and non – neoplastic (NN) lesions, with specific characteristics and classifications. However, few studies have been oriented to determine the clinical impact of p-CLE for diagnosis and management in patients with diagnostic doubts.

Aims & Methods: The aim of this study is to put in evidence the clinical impact of p-CLE in this group of patients. Prospective study, performed from November 2013 to November 2014, in consecutive patients in whom p-CLE (Cellvizio®, Mauna Kea Technology) was indicated due to diagnostic doubts (absence of endoscopic–histological relationship). Baseline characteristics, indications, previous diagnosis studies, findings at p-CLE, clinical management and histopathological outcomes were evaluated. Indications for p-CLE were N and NN lesions. Lesions include: adenomas, dysplasia or cancer located in any gastrointestinal tract level, Barrett's esophagus, inflammatory bowel disease or pancreatic cysts. Previous diagnostic studies included: high definition magnification with digital chromoendoscopy, ERCP with brushing, EUS. Other studies were: CT-scan, cholangiography by MRI, tumor markers. Interventions based on the findings of p-CLE were analyzed according to the records, and included: drug treatment, other diagnostic studies, endoscopic or surgical treatments. The diagnostic yield was determined thought sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and match measurement. Diagnostic and therapeutic management, redirection of biopsies and need of other diagnostic methods were evaluated.

Results: 43 patients were included. 51% were male (22/43) with mean age of 49 ± 19 years. N lesions were 37% (15/43) of cases, located at: stomach (6), esophagus (4), bile duct (3) and colon (2). The sensitivity was 87% and specificity of 93%,(AUC=0.9582) with a PPV of 87% and NPV 93%. p value <0.05. The observed concordance was 90.6% with a Kappa value of 0.80, corresponding to a force of substantial agreement according to Landis & Koch criteria. Changes in diagnostic and therapeutic approach were evident in 39.5% of cases (17/43), directing the sampling in 100% of cases (17/17) and avoiding diagnostic or therapeutic methods in all cases.

Conclusion: p-CLE is an essential diagnostic tool for patients with diagnostic doubts, as it allows in-vivo display cell and helps to direct biopsies. It has a significant clinical impact on the diagnosis and treatment of patients.

Disclosure of Interest: None declared

P0126 PERIODIC ENDOSCOPIES DID NOT INCREASE THE DETECTION OF EARLY GASTRIC CANCER IN A YOUNG POPULATION

C. H. Park¹, E. H. Kim², H. Chung², J. C. Park², S. K. Shin², Y. C. Lee², S. K. Lee²

¹Department of Internal Medicine, Hanyang University College of Medicine, Guri, ²Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea

Contact E-mail Address: yesable7@gmail.com

Introduction: Screening endoscopies in individuals 40 years or older in regions where gastric cancer is prevalent increase the diagnosis of gastric cancer at an early stage. However, the benefits of screening endoscopies in a young population (<40 years) have not been evaluated.

Aims & Methods: We reviewed data from patients less than 40 years old who underwent endoscopic submucosal dissection (ESD) or surgery for initial-onset gastric. We also administered a questionnaire to gather information concerning periodic endoscopic inspections and the period from the penultimate endoscopy to diagnosis.

Results: Of the 564 patients in this study, 101 (17.9%) and 36 (6.4%) patients had undergone screening endoscopies within 24 months and 60 months of gastric cancer diagnosis, respectively. The proportion of patients with early gastric cancer (EGC) was 67.6%, 83.3%, and 64.3% in the ≤24 months, 24 to 60 months, and >60 months groups, respectively (P=0.063). On multivariable analysis, periodic endoscopies did not influence early diagnosis of gastric cancer (with >60 months as the reference group: ≤24 months, odds ratio [OR] = 0.992, 95% CI = 0.614–1.603; 24–60 months, OR = 2.238, 95% CI = 0.891–5.625). However, the proportion of lesions treated with ESD did differ according to the interval between endoscopic examinations (P=0.048).

Conclusion: Although periodic endoscopies increased the proportion of patients with EGC that was treated with ESD, they did not increase the proportion of patients diagnosed with gastric cancer that was determined to be EGC in a young population.

Disclosure of Interest: None declared

P0127 CLINICAL OUTCOME OF ABSOLUTE VERSUS EXPANDED INDICATION OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY GASTRIC CANCER: SINGLE CENTER STUDY

C. B. Ryu¹, M. S. Lee¹, C. S. Shim², J. Y. Bae³

¹Department of Internal Medicine, Soon Chun Hyang University School of Medicine, Bucheon, ²Department of Internal Medicine, Glocal Digestive Disease Center, Konkuk University School of Medicine, ³Department of Internal Medicine, Seoul Medical Center, Seoul, Republic of Korea

Contact E-mail Address: ryuchb@gmail.com

Introduction

Background: The treatment of early gastric cancer (EGC) by endoscopic submucosal dissection (ESD) has been rapidly gaining popularity in Korea. Current guidelines for endoscopic management such as EMR and endoscopic submucosal dissection (ESD) in early gastric cancer (EGC) are in evolution, with broader indication criteria. In Korea, indication of ESD for early gastric cancer have been still one of big issue.

Aims & Methods

Aim: The purpose of this retrospective comparative study was to evaluate clinical outcome of ESD for EGC, based on absolute indication and expanded indication criteria,

Method: ESD was performed on 1102 cases of early gastric neoplasm (cancer: 631, dysplasia: 471) from Jan 2002 to Aug 2011 at Soon Chun Hyang University Bucheon Hospital.

According to final diagnosis, EGCs below were enrolled by two groups (absolute vs expanded) and followed up: absolute: differentiated intramucosal (IM) cancer less than 20 mm, expanded: differentiated-type intramucosal cancer less than 30 mm in diameter or minute sm invasion (< 500 µm from the muscularis mucosa) or undifferentiated IM cancer less than 10 mm.

Results: En bloc and complete resection rate in absolute and expanded group were 94.1% vs 90.7%, 93.7% vs 88.5% (NS). Size of lesion was 12.7 ± 4.8 mm, 26.6 ± 13.0 mm (p < 0.05). Complication such as bleeding and perforation was no statistical difference (p > 0.05). There was no between-group difference in the local recurrence rate (1.4% vs1.8%; NS) at a median follow-up period of 28 months (interquartile range 6-48 months).

Conclusion: Higher en bloc resection and complete resection rate, lower complication and recurrence in expanded group of ESD for EGC revealed as absolute group.

We concluded indication of ESD for EGC can be expanded.

Disclosure of Interest: None declared

P0128 CAUSTIC INGESTION: PREDICTIVE FACTORS FOR ESOPHAGEAL STENOSIS DEVELOPMENT - A MULTICENTER EXPERIENCE

C. Teixeira¹, A. Antunes², S. Ribeiro¹, M. Eusebio², A. L. Alves¹, B. Peixe³, H. Guerreiro³, A. P. Oliveira¹

¹Gastrenterology, Centro Hospitalar de Setubal, Setubal, ²Gastrenterology, Centro Hospitalar do Algarve – Polo de Faro, ³Gastrenterology, Centro Hospitalar do Algarve – Polo de Faro, Faro, Portugal

Contact E-mail Address: ac.corda.teixeira@gmail.com

Introduction: There is an increasing incidence of caustic substances ingestion in the Western Countries, carrying a high risk of luminal strictures.

Aims & Methods: Identify predictive factors for the development of esophageal stenosis, and evaluate the effect of corticoteraphy and antibiotic therapy in reducing that risk. Multicentric retrospective study, that reviewed all the patients who ingested caustic substances and were admitted to our centers over a period of 10 years. Demographic, clinical, analytical, endoscopic (Zargar score) data were obtained. Univariate and multivariate logistic regression analysis was performed.

Results: 133 patients, 67 females, mean age 49, of whom 100 were hospitalized (median: 6 days). During follow up, 20 patients developed strictures, (esophagus: 90%), predominantly after alkaline substances ingestion (83%). Strong alkali (p=0.000), esophageal lesions Zargar 2B (p=0.002) and Zargar 3A (p=0.001), invasive ventilation (P=0.012), oral feeding after 48h (p=0.003) and total parenteral nutrition (TPN) (p=0.000) were independent risk factors for esophageal stenosis. Delay in the oral feeding had a moderate correlation for stricture development (rs=0.422;p=0.00). Corticotherapy (p=0.031) and antibiotic therapy (p=0.001) were not associated with risk reduction. Age, strong acid, intentionality and recurrence of ingestion were not associated with stricture risk (p > 0.05). Multivariate analysis revealed that only strong alkali (OR=18,81), TPN (OR=6,6) and esophageal lesions Zargar-2B (OR=7,18) and Zargar-3A (OR=12,12) maintained statistical significance.

Conclusion: There was a higher risk of esophageal stenosis with strong alkali ingestion and with higher severity of endoscopic lesions. Corticotherapy and antibiotic therapy were not associated with risk reduction. Our study suggests a potential cytoprotection effect of early oral feeding in esophageal stenosis risk reduction.

Disclosure of Interest: None declared

P0129 IS ENDOSCOPIC SUBMUCOSAL DISSECTION FOR SPORADIC NON-AMPULLARY DUODENAL ADENOMA/CARCINOMA ESSENTIAL IN TERMS OF LONG-TERM CLINICAL OUTCOMES?

D. Maruoka¹, M. Arai¹, H. Ishigami¹, K. Okimoto¹, T. Matsumura¹, T. Nakagawa¹, T. Katsuno¹, O. Yokosuka¹

¹Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba City, Japan

Contact E-mail Address: d-maruoka@biscuit.ocn.ne.jp

Introduction: The number of endoscopic submucosal dissections (ESD), as well as endoscopic mucosal resection (EMR), performed for sporadic non-ampullary duodenal adenoma/carcinoma (SNADA) has recently increased. EMR for SNADA is a comparatively safe procedure, but there are concerns regarding local recurrence, due to a non-R0 resection or piecemeal resection. On the other hand, ESD for SNADA is excellent for en-bloc resection; however, the rate of complications in the duodenum, such as perforation, is much higher than that in the rest of the digestive tracts. Moreover, the indications for duodenal ESD are highly controversial. We therefore analyzed the necessity of ESD for SNADA from the perspective of long-term clinical outcomes and complications.

Aims & Methods: We retrospectively evaluated 82 patients, who underwent endoscopic resection, and who were histopathologically diagnosed as SNADA between May 2004 and February 2015 at our institution. Of 87 lesions, the final pathological diagnoses were low-grade dysplasia, high-grade dysplasia, and adenocarcinoma, in 23, 30, and 34, respectively; in all cases of adenocarcinoma, the disease had invaded up to the mucosal layer. The mean size of the lesions was 10.5 ± 5.7 mm. The numbers of lesions resected by polypectomy, EMR, strip biopsy, EMR with a cap-fitted panendoscope (EMR-C), and ESD were 1, 35, 9, 31, and 11, respectively.

Results: Eighty lesions were endoscopically followed up at least once after endoscopic resection (mean follow up period [months], 32.9 ± 28.5; range, 3–111), and 67 were followed up endoscopically for more than 1 year (mean follow up period [months], 38.2 ± 28.2; range, 12–111). The overall rate of R0 resection was 46.0% (40 of 87), and that of en-bloc resection was 77.0% (67 of 87). The rate of intraprocedural perforation was 3.4% (3 of 87), all of which occurred during ESD; the rate of intraprocedural perforation of ESD was 27.3% (3 of 11), which was significantly higher than that of the rest of the procedures (vs. 0% [0 of 76]; p < 0.001, chi-square test). There was only 1 case (1.3%) of local recurrence after resection; this was a case of piecemeal EMR for intramucosal carcinoma in 2 segments, and the recurrent lesion was resected by EMR 3 months after the initial resection, with no re-recurrence. Of the 67 lesions which were endoscopically followed up for longer than 1 year, the recurrence-free rate was 98.5% (66 of 67); the recurrence-free rates for cases of non-R0 and piecemeal resection were 97.5% (39 of 40, 12–95 months) and 91.7% (11 of 12, 12–89 months), respectively. There were no cases of distant recurrence or death from SNADA.

Conclusion: In terms of long-term clinical outcomes, the prognosis of the patients who underwent resection of SNADA with ESD was excellent; the patients who underwent resection of SNADA with non-R0 or piecemeal resection also had a favorable long-term prognosis, because of the rarity of recurrence. We think that reconsideration of the indications for ESD for SNADA is necessary, given the high frequency of complications with ESD.

Disclosure of Interest: None declared

P0130 INTRAGASTRIC MIGRATION OF LAPAROSCOPIC ADJUSTABLE GASTRIC BANDING. ENDOSCOPIC TREATMENT IS ALWAYS FEASIBLE. THE EXPERIENCE OF A SPANISH NON TERTIARY HOSPITAL

D. Collado¹, L. R. Rábago¹, L. Alonso Castillo¹, A. Ortega¹, M. Perez¹, M. Arias¹, J. Vazquez Echarri², N. Herrera²

¹Gastroenterology, ²surgery, Hospital Severo Ochoa, Leganes, Spain

Contact E-mail Address: lrabagot@gmail.com

Introduction: Intragastric band migration is an uncommon complication of Laparoscopic Adjustable Gastric Banding (LAGB) (0.5-11%) usually resolved by a surgical approach. We describe our experience .

Aims & Methods: Since 2001 we treated 127 morbid obese patients (pts) by LAGB. Patients with migration of gastric band into stomach more than 50% of circumference were able to be treated. The procedure was performed under general anesthesia. It is not necessary to use fluoroscopy.

Procedure: The band is cut using the wires from mechanical lithotripsy basket (MTW) or a 0.035 standard guidewire. Second the wire is looped about the visible band, grasped by the alligator forceps and brought out through the patient’s mouth. Then the guidewire two ends are placed into the metal sheath of the mechanical lithotriptor (MTW) in order to cut it. The surgeon excised and removed the tubing and external port. Finally the split band is removed using a polypectomy snare, usually with a gentle pulling back from the esophagus.

Results: We found that 11 out of 127 LAGB (8.6%) become symptomatic due to gastric migration. 88.8% were females with average age of 42.6 yo. The time between the band placement and endoscopic removal was 60.5 months.

The symptoms were epigastric pain and weight regain as a sign of band dysfunction. Three pts were operated, one refused endoscopic treatment and the others were operated by band dysfunction finding out the gastric migration. 7 out of 9 LAGB (77.7%) were endoscopically removed in one session. We had two failures, 1 out of 9 LAGB (11.1%) was not possible to cut and the other (11.1%) was split but not removed due to difficulties with ventilation by excessive gas insufflation. His recovery from the attempt was uneventful and she remains well after 7 years of follow up, waiting for their possible complete migration. No complications were noticed after the endoscopic removal and pts were discharged in average of 2.6 days (17). The band removal was accomplished in three steps: a) cutting the band of silicone in the middle part avoiding the plastic part near the external tube, b) seizing the end of the split band near the external tube, coming from the port and c) pulling the endoscope out steadily and forcefully to liberate the band from the gastric wall.

Conclusion: More than 8.6% of LAGB will have gastric migration and develop symptoms. The endoscopic removal of LAGB is feasible, safe, but not easy, being a good alternative to surgery. We were able to remove 77.7% of LAGB, but the band should be migrated more than 50%. It is important to know very well the removal technique and their tricks. It is not necessary the use of intraoperative fluoroscopy and it seems to be safe to cut the band without its removal.

Disclosure of Interest: None declared

P0131 ENDOSCOPIC TREATMENT OF FISTULAS AFTER BARIATRIC SURGERY: EXPERIENCE OF A SINGLE CENTER

D. F. B. Carvalho¹, R. Loureiro¹, P. Russo¹, C. Bernardes¹, I. Seves¹, R. Rio-Tinto¹

¹Gastroenterology, Hospital Santo António dos Capuchos, Lisbon, Portugal

Contact E-mail Address: dianafbcarvalho@gmail.com

Introduction: Bariatric surgery is the most effective treatment for long-term resolution of obesity and its co-morbidities. The complexity of the procedure and the surgical risk in obese patients is associated with significant morbidity and mortality. Fistulas in suture sites are the most serious complications and their best therapy approach is not yet defined. In the literature there are several small series and descriptions of cases in which self-expandable metallic stents (SEMS) are used for fistulas’ treatment, proving to be an effective and safe alternative to surgery.

Aims & Methods: The authors aim to evaluate the efficacy and safety of SMES in the treatment of fistulas after bariatric surgery.

Retrospective analysis of patients who underwent SEMS (uncovered or partially covered) placement for treatment of fistulas after bariatric surgery between 01/01/2010 and 31/12/2014.

Results: Ten patients (p) were included, 80% women, mean age 40 years (26-62). Sleeve was performed in 9p and gastric-jejunal bypass in one. Mean time between the surgery and fistula diagnosis was 34 days (10-67). In 6p uncovered SEMS was used and in 4p partially covered SEMS. Completed fistula closure in 9p (90%), being necessary to relocate the SEMS in one case and to place a second stent in other. Surgery was performed in one patient in which the fistula persisted 49 days after the stent placement. SEMS remained in situ for a mean time of 70 days (24-105). In the patient submitted to gastric-jejunal bypass stent late migration occurred with obstruction and consequent removing by double-balloon enteroscopy. SEMS withdrawal in the remaining cases was performed by traction (5p) or by placement of a plastic stent with extraction in bloc after 2 weeks (3p), without complications.

Conclusion: The endoscopic treatment of fistulas after bariatric surgery is an effective and safe alternative to surgery, with clinical sucess of 90% in this series.

Disclosure of Interest: None declared

P0132 TOO MANY PREDICTIVE SCORES FOR UPPER GASTROINTESTINAL BLEEDING – SHOULD WE USE THEM AT ALL?

D. Branquinho¹, R. Cardoso¹, C. Gregório¹, C. Sofia¹

¹Gastroenterology, Coimbra University Hospital (CHUC), Coimbra, Portugal

Contact E-mail Address: diogofbranquinho@yahoo.com

Introduction: Despite the irreplaceable role of esophagogastroduodenoscopy (EGD) in the diagnosis of upper gastrointestinal bleeding (UGB), it is frequently hard to establish the ideal timing to perform it. The need of therapeutic intervention and the risk of relapse are also often difficult to predict. Several scores have been described with this purpose, but a comparison between them is seldom considered.

Aims & Methods: To identify clinical predictors of the need to undertake therapeutic endoscopic procedures, the best timing to execute them and the risk of relapse.

From January to April 2014, all patients submitted to EGD due to suspected UGB were included. Clinical and endoscopic variables from 141 patients were collected. Endoscopic scores such as Rockall, Glasgow-Blatchford and AIMS65 were calculated.

Results: A total of 141 patients were included, with an average age of 68.1 ± 16.3 years old, 65.2% being males. Endoscopic therapeutic intervention was needed in 62 patients (44%), 16 had a relapse (10.6%) and 3 eventually died (2.1%).

The need to perform therapeutic maneuvers was bigger in patients presenting with hematemesis (69.4% vs. 38.6%; p=0.003), chronic liver disease (62.2% vs.37.5%; p=0.009), hypoalbuminemia (69.4% vs. 38.6%; p=0.003) e in those with significant rise in blood urea nitrogen (BUN) levels (41.8 ± 24.1 vs. 34.4 ± 26.0mg/dL; p=0.009). In multivariate analysis, only hematemesis and elevated BUN kept their predictive value. In ROC curves, only pre-endoscopic Rockall score had an acceptable performance: AUC 0.664 (CI:0.561-0.768).

As for relapse, multivariable analysis showed that patients presenting with hematemesis (18.5% vs. 3.9%; p=0.005) and hypoalbuminemia (22.2% vs. 2.9%; p=0.001) had considerably bigger risk of rebleeding.

Conclusion: Clinical presentation with hematemesis, a bigger rise in BUN levels and pre-endoscopic Rockall score showed the ability to predict the need of endoscopic therapy. The best predictors of UGB relapse were AIMS65 score, hypoalbuminemia (<3g/dL) and altered mental status.

Disclosure of Interest: None declared

P0133 FLEXIBLE ENDOSCOPIC MYOTOMY IS SAFE AND EFFECTIVE FOR ZENKER'S DIVERTICULUM (ZD): RESULTS FROM A TERTIARY REFERRAL CENTER

C. Leberre¹, M. Le Rhun¹, N. Musquer¹, C. Trang¹, S. Bruley des Varannes¹, E. Coron¹

¹Institut des Maladies de l'Appareil Digestif, University Hospital, Nantes, France

Contact E-mail Address: emmanuel.coron@gmail.com

Introduction: Flexible endoscopic treatment for Zenker's diverticulum (ZD) aims at performing a myotomy of the cricopharyngeal muscle on the septum in symptomatic patients. Because this technique is still not widely spread, data regarding its real efficacy in routine practice are still lacking. Our aim was to assess the feasibility, complication rates and the efficacy of flexible endoscopic treatment in patients referred for symptomatic ZD.

Aims & Methods: Medical records of all patients referred to our Department for flexible endoscopic treatment of ZD were retrospectively reviewed. Procedures were performed with a flexible gastroscope (Fujifilm EG530, Japan or Olympus Gif 180/190, Japan). After performing a diagnostic endoscopy, a soft overtube (ZDO-22-30, Cook, Ireland) was inserted over the scope to stabilize the gastroscope over the septum. Under endoscopic surveillance, a myotomy of the cricopharyngeal muscle was performed using a Zimmon needle connected to a surgical generator. After performing the myotomy, 2 clips were placed on the distal edge of the myotomy to prevent leakage into the mediastinum. Patients were discharged on the following day with oral antibiotics and alimentary recommendations. Patients’ clinical characteristics, occurrence of complications as well as evolution of digestive symptoms were analysed.

Results: Between 2009 and 2014, 16 patients (8M/7F; mean age 73 years, range 54-97years) underwent flexible endoscopic treatment of ZD at the University Hospital of Nantes, France. Mean size of ZD was 36 mm (range 20-60mm). One case of mediastinitis occurred, which was successfully treated with radiological drainage. No other complication was noted. Prevalence of dysphagia, regurgitation and chronic cough dropped from 80%, 67% and 47% of patients to 27%, 27% and 7%, respectively. Odynophagia and/or dysphonia were initially present in 13% of patients and completely disappeared (0%) after endoscopic treatment. In 3 patients, symptoms recurrence (1 to 7 months) led to further treatment, either by 1-2 endoscopic session(s) (n=2) or surgical ZD resection (n=1).

Conclusion: Flexible endoscopic myotomy was relatively safe and effective for Zenker's diverticulum in this single centre study. Provided multicenter studies confirm these results, flexible endoscopic myotomy might be used as a first-line therapy in symptomatic patients in centers performing interventional endoscopy.

Disclosure of Interest: None declared

P0134 EFFICACY AND SAFETY OF ENDOSCOPIC MUCOSAL RESECTION (EMR) IN SUPERFICIAL OESOPHAGEAL SQUAMOUS CELL CARCINOMA (SCC): RESULTS FROM A MULTICENTER STUDY

M. Jacolot-Benestan¹, N. Etchepare², F. Cholet¹, M. Le Rhun², J. Jezequel¹, N. Musquer², Y. Touchefeu³, L. Doucet⁴, M. Robaszkiewicz¹, E. Coron²

¹Department of Gastroenterology and Hepatology, University Hospital, Brest, ²Institut des Maladies de l'Appareil Digestif, ³Institut des Maladies de l’Appareil Digestif, University Hospital, Nantes, ⁴Department of Digestive Pathology, University Hospital, Brest, France

Introduction: Squamous cell carcinoma (SCC) is frequent but data are scarce regarding endoscopic mucosal resection (EMR) in these patients. Data from studies on EMR in Barrett’s oesophagus are specifically different and cannot be transposed to SCC because 1) SCC patients generally have severe specific co-morbidities and 2) SCC lesions have a higher risk of lymph node invasion. Therefore, our aim was to specifically evaluate the complication rate and efficacy of EMR in a large cohort of patients referred for superficial SCC.

Aims & Methods: We retrospectively selected all patients undergoing esophageal EMR for SCC at the University Hospitals of Nantes and Brest, France. EMR was performed on lugol-negative lesions with previous biopsies showing dysplasia or carcinoma. Clinical, endoscopic and histologic data were analyzed using medical records. Complication rates, recurrence and overall survival were reviewed as the main outcome measurements.

Results: In total, 78 patients (62M/16F; mean age 65 years) with SCC were treated by EMR from 1998 to 2014. Three complications occurred (2 perforations, 1 delayed bleeding), which were all successfully managed by endoscopy. Histological assessment of the EMR specimen confirmed epithelial carcinoma (n=27), intramucosal carcinoma (n=8), muscularis mucosae invasion (n=15) or submucosal invasion (n=22). The deep margin was R0 in 78% of cases. Due to submucosal invasion, 4 and 11 patients underwent subsequent surgery or radiochemotherapy, respectively. During follow-up (mean duration 35 months), recurrence occurred in 24% of cases. Overall survival rates at 1, 3 and 5 years were 90%, 74% and 59%. The 3-year disease free survival was 74%. Only 7.7% of patients died from an evolution of the oesophageal cancer.

Conclusion: In our study, EMR had a very low rate of complications and allowed curative resection in more than 75% of cases, with good long-term overall survival and disease-free survival in patients with SCC. In case of submucosal invasion, EMR was also useful to discuss surgery or radiochemotherapy. Therefore, EMR should be considered as a first-line modality to stage and potentially cure superficial SCC. Future prospective studies should establish the exact role of other promising endoscopic techniques such as endoscopic submucosal dissection in comparison with EMR.

Disclosure of Interest: None declared

P0135 SAFETY AND EFFICACY OF GLYCOPYRROLATE AS A PREMEDICATION FOR ENDOSCOPIC SUBMUCOSAL DISSECTION: A PRELIMINARY REPORT (A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY)

E. J. Kim¹, S. Y. Kim¹, J. H. Kim¹, J. W. Chung¹, Y. J. Kim¹, K. A. Kwon¹, D. K. Park¹, K. O. Kim¹

¹Department of Gastroenterology, Gachon University, Gil Medical Center, Incheon, Republic of Korea

Contact E-mail Address: imetkim@gilhospital.com

Introduction: Endoscopic submucosal dissection (ESD) requires a high level of technique as well as a longer procedural time than conventional endoscopic procedures. Occasionally large amount of salivary and bronchial secretion can induce hypoxemia or sudden coughing during endoscopic procedure. Therefore there is a necessity to reduce oral or bronchial secretion. Anti-muscarinic anticholinergics suppress salivary and bronchial secretion and glycopyrrolate is one of the potent anti-muscarinic anticholinergics.

Aims & Methods: In the present study, a double blind, randomized, placebo-controlled trial, we investigated the efficacy and safety of glycopyrrolate premedication for ESD at a single tertiary medical center. A total of 59 patients undergoing ESD at a single tertiary medical center, from December 2014 to April 2015 were randomly allocated to receive one of the two premedications: glycopyrrolate (0.004 mg/kg, IM); or placebo (2.0ml of normal saline solution, IM). All patients received premedication 30 minutes before ESD in double-blind manner. The endoscopist reported the amount of secretions, cough, hypoxemia, procedure time and other procedure related adverse events after the procedure. The secretion assessment of the endoscopist was reported with predefined grading scale from zero indicating no secretion to four indicating large amount of secretion which cannot be controlled with suction.

Results: A total of 28 patients received glycopyrrolate, and 31 patients received placebo. ESD was successfully conducted in all patients without serious adverse events related to sedation or ESD. The proportion of the patients with the secretion score more than three points was lower in the glycopyrrolate group than in control group. (14.3% vs 32.3%), which was not statistically significant (p=0.133). The hypoxemia during ESD was observed in 9.7% of the control group and 10.7% of the glycopyrrolate group, which was not statistically significant (p=1.0). The proportion of the patients with cough during procedure was 41.9% for the glycopyrrolate group and 25% for the control group, which was not statistically significant (p=0.170). No other procedure or premedication related complications were observed in both groups.

Conclusion: In this preliminary report, the use of glycopyrrolate as a premedication for the ESD reduced the salivary and airway secretion, however there was no statistically significant difference between two groups. Similarly incidence of hypoxemia and cough was not significantly different. Further studies with larger sample sizes are necessary to investigate the safety and efficacy of glycopyrrolate as a premedication for endoscopic procedure.

Disclosure of Interest: None declared

P0136 ROUTINE ENDOSCOPIC SCREENING FOR SYNCHRONOUS ESOPHAGEAL NEOPLASM IN PATIENTS WITH HEAD AND NECK SQUAMOUS CELL CARCINOMA: A PROSPECTIVE STUDY

E. J. Gong¹, D. H. Kim¹, J. Y. Ahn¹, K.-S. Choi¹, K. W. Jung¹, J. H. Lee¹, K. D. Choi¹, H. J. Song¹, G. H. Lee¹, H.-Y. Jung¹, J. H. Kim¹

¹Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea, Seoul, Republic of Korea

Contact E-mail Address: gong-eun@hanmail.net

Introduction: Early detection of synchronous esophageal squamous cell neoplasm (ESCN) in head and neck squamous cell carcinoma (HNSCC) patients can significantly affect their prognosis.

Aims & Methods: Subjects who were diagnosed as HNSCC from May 2010 to January 2014 were eligible. All patients underwent conventional white light endoscopic examinations with narrow band imaging and Lugol chromoendoscopy.

Results: Among 458 subjects screened, 28 synchronous ESCN, including 18 dysplasias and 10 squamous cell carcinomas, were detected in 24 patients (5.2%). The incidence of ESCN was greatest in patients with hypopharyngeal cancer (20.9%), followed by laryngeal cancer (3.8%), oropharyngeal cancer (2.8%), and oral cavity cancer (0.9%). In multivariate analysis, pyriform sinus involvement was independent risk factor for developing synchronous ESCN (odds ratio 171.2, p<0.001). Most patients with synchronous ESCN (22/24, 91.7%) were early stage, and 16 patients (66.7%) received treatment with curative intent. During the follow-up period (median, 24 months), the 3-year overall survival rates was significantly lower in patients with ESCN than in patients without ESCN (54.2% vs. 78.3%, p=0.0013).

Conclusion: Routine endoscopic screening for detecting synchronous ESCN should be recommended for patients with HNSCC, especially those with pyriform sinus involvement.

Disclosure of Interest: None declared

P0137 ENDOSCOPIC PAPILLECTOMY: FEASIBILITY, SAFETY AND EFFICACY DATA FROM A SINGLE UK CENTRE

K. Kandiah¹, F. Chedgy¹, A. Kumar¹, R. Bhattacharyya¹, P. Goggin¹, P. Bhandari¹

¹Gastroenterology, Queen Alexandra Hospital, Portsmouth, United Kingdom

Contact E-mail Address: kesavankandiah@gmail.com

Introduction: Endoscopic papillectomy is an alternative to radical surgery (10% mortality risk) in the management of ampullary adenomas. Very few centres in the UK have the expertise or experience of performing this procedure and there is certainly no published literature from the UK.

Aims & Methods: We aim to report outcomes after endoscopic papillectomy in a single tertiary endoscopy unit in the UK. The prospectively collected data of all patients who underwent endoscopic papillectomy between 2005 and 2015 in Queen Alexandra Hospital, Portsmouth were reviewed. All procedures were carried out by PB (papillectomy) and PG (ERCP) using a standard duodenoscope. The pancreatic and biliary ducts were cannulated. A dilute methylene blue dye was injected into the pancreatic duct prior to papillectomy. Submucosal injection was performed in all cases prior to snare resection of the ampullary neoplasia. 5 Fr pigtail pancreatic stent insertion was attempted in all cases after resection of the neoplasia.

Results: A total of thirty-five patients were referred for papillectomy but only twenty-two patients (13 female, median age 72 years) underwent a total of 24 papillectomies. En-bloc resection was achieved in 17 patients (77%) with lesion sizes ranging from 8 - 25mm (Median 16mm). Pancreatic stent placement was successful in 82% of all papillectomies. Three patients experienced complications (12.5%); 2 bleeding and 1 acute pancreatitis. There was no procedure-related deaths and no one required emergency surgery. There were no local recurrences in 77% of patients. Two patients required 2 attempts to achieve complete clearance of their adenomas. Histology of the resected lesions revealed low grade dysplasia (54.6%), high grade dysplasia (27.2%), cancer (9%), gangliocytic paraganglioma (4.6%), and neuroendocrine tumour (4.6%). Of the two patients who were found to have invasive cancer, the first patient went on to have a pancreaticoduodenectomy and subsequently died of post-operative complications and the second patient was palliated. The total curative resection rate was 86%.

Conclusion: This is the largest reported UK series of endoscopic papillectomy. Our data demonstrates that this method is a feasible, safe and efficacious means of treating ampullary neoplasia in expert hands. It obviates the need for pancreaticoduodenectomy with its inherent morbidity and mortality. Complications can be serious and expertise is required to deal with them.

Disclosure of Interest: None declared

P0138 DEVELOPMENT AND VALIDATION OF AN ONLINE TRAINING MODULE IN THE USE OF ACETIC ACID TO DETECT BARRETT’S NEOPLASIA

F. J. Q. Chedgy¹, K. Kandiah¹, R. Bhattacharyya¹, H. Barr², J. De Caestecker³, S. Green⁴, C. Gordon⁵, A. Li⁶, G. Sadler⁷, G. Longcroft-Wheaton¹, P. Bhandari¹

¹Gastroenterology, Queen Alexandra Hospital, Portsmouth, Portsmouth, ²Surgery, Gloucester Royal Infirmary, Gloucester, ³Gastroenterology, Leicester General Hospital, Leicester, ⁴Gastroenterology, Royal Sussex County Hospital, Brighton, ⁵Gastroenterology, Royal Bournemouth and Christchurch Hospital, Bournemouth, ⁶Gastroenterology, Worthing Hospital, Worthing, ⁷Gastroenterology, St George's Hospital, London, United Kingdom

Contact E-mail Address: ferguschedgy@yahoo.co.uk

Introduction: Acetic acid enhances the ability to correctly identify Barrett’s neoplasia and is increasingly used by both expert and non-expert endoscopists. However, despite its increasing use, there is no validated training strategy to achieve competence.

Aims & Methods: The aim of our study was to develop a validated online training tool for acetic acid assisted Barrett’s neoplasia detection and prospectively evaluate its impact and effectiveness. Video libraries of acetic acid assisted chromoendoscopy (AAC) were analysed. The best still images and videos were identified and correlated to histology. These images and videos were validated for quality and accuracy by 3 independent experts in AAC and 3 AAC naïve endoscopists. An online training module was developed.

13 Endoscopists with varying degrees of experience in the use of AAC participated in the study. Participants initially completed an online test consisting of 40 still images and 20 videos of Barrett’s oesophagus with and without neoplasia. No feedback was given. Following this, the participants completed an online training module on the use of AAC. Having completed the training module, participants then repeated the test.

Results: We observed a significant difference in accuracy (p=0.006) between experts (0.93; 95% CI, 0.84-1.00) and novices (0.76; 95% CI, 0.70-0.82) during the validation exercise. The training tool led to a significant improvement in accuracy for all endoscopists with a mean pre-training score of 76% rising to 83% (p=0.013) after training. The training intervention with our tool led to a significant improvement in the confidence of the endoscopist in the use of acetic acid with the mean pre-training confidence level rising from 2.5 (5 point scale) to 3.9 post-training (p < 0.001). The training module led to a significant shift to the willingness of the endoscopists in changing practise from Cleveland clinic protocol to acetic acid guided targeted biopsy protocol with mean pre-training score of 2.6 (5 point scale) rising to 3.8 post-training(p < 0.001).

Conclusion: 1. We were successful in developing and validating an online training and testing tool for acetic acid chromoendoscopy for Barrett’s neoplasia.

2. Low pre-training scores amongst users and non-users demonstrated the need for training tool.

3. Training intervention with our tool improves the accuracy of endoscopists in the use of acetic acid to detect Barrett’s neoplasia proving the efficacy of this tool.

4. The training tool increases the endoscopist’s degree of confidence in the use of AAC.

5. The training tool also leads to shift in attitudes of endoscopists from Cleveland clinic protocol towards AAC guided biopsy protocol for Barrett’s surveillance.

Disclosure of Interest: None declared

P0139 ENDOSCOPIC OVER-THE-SCOPE CLIP SYSTEM FOR TREATMENT OF PERFORATED PEPTIC ULCER: FIRST CLINICAL EXPERIENCES

F. Swahn¹, L. Lundell², F. Hammarqvist², G. Sandblom², U. Arnelo²

¹Department of Surgery, Skane University Hospital, Clinical Sciences Lund, Lund, ²Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden

Contact E-mail Address: fredrik.swahn@ki.se

Introduction: Perforated peptic ulcer disease is a severe surgical emergency that carries high mortality and morbidity rates. The standard treatment has been prompt surgical closure of the perforation and control of extraluminal fluid collections. Hereby we report on 12 patients with gastric or duodenal peptic ulcer perforations who were managed by a novel therapeutic concept, i.e. endoscopic over-the-scope clip (OTSC) system.

Aims & Methods: All patients were treated at the OR under general anesthesia with readiness for laparotomy if endoscopic management would fail. The endoscopic OTSC system (10 mm) was combined with a twin-grasper (Ovesco Endoscopy AG, Tübingen Germany) in order to approximate the edges of the ulcer, whereupon the OTSC was applied. The procedure was supplemented with intra-abdominal lavage using 2 litres of lukewarm saline instilled through an infra umbilical drain and subsequently evacuated. The efficacy of the closure was documented by installing some methylene blue through a naso-gastric tube during the procedure and on the first postoperative day (POD). If there were no signs of blue colour in the drainage at POD 1, the drain and the naso-gastric tube were removed and per oral feeding started. A follow-up endoscopy was performed on POD 4. During 2010-2015 we treated 12 patients (median age 72, range, 33-89; 9 men, 3 women) with intention to treat at the time when CT-scan revealed free air in the abdominal cavity.

Results: Ten out of twelve patients (83%) were successfully treated with endoscopic closure at the first attempt. Two patients were directly converted to surgery due to complex perforation and hard surrounding tissue, which made it impossible to grasp the edges. Follow-up endoscopy at POD 4 demonstrated intact closure in all 10 cases.

In patients (n=5) with a short perforation history and mild degree of abdominal contamination, the postoperative period was smooth and associated with short hospital stay (4-5 days). In elderly and frail patients and in those with extensive abdominal contamination a greater need for additional percutaneous drainage of fluid collections, intensive care and prolonged antibiotic treatment were required. No mortality was recorded.

Conclusion: Endoscopic OTSC closure of perforated peptic ulcer disease can be an alternative in selected cases, particularly in patients with short medical history of perforation irrespectively of comorbidity and age.

Disclosure of Interest: None declared

P0140 SAFETY AND EFFICACY OF A NEW THERAPEUTIC LASER SYSTEM FOR HEMOSTATIC TREATMENTS IN LUMINAL GI ENDOSCOPY – FIRST RESULTS IN AN ESTABLISHED ANIMAL MODEL

G. E. Tontini¹, H. Neumann², L. Carmignani³, B. Bruni⁴, L. Pastorelli¹⁵, F. Cavallaro¹, F. Fagnani⁶, C. Clemente⁴, M. Bottani¹, M. Vecchi¹⁵

¹Gastroenterology and Digestive Endoscopy Unit, IRCCS Policlinico San Donato, Milano, Italy, ²Department of Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany, ³Academic Urology Department, ⁴Pathology and Citodiagnostic Unit, IRCCS Policlinico San Donato, ⁵Department of Biomedical Sciences for Health, University of Milan, Milano, ⁶Surgical Division, Quanta System S.p.A, Varese, Italy

Contact E-mail Address: gianeugeniotontini@libero.it

Introduction: The Thulium laser system is an established therapeutic technology for surgical resection [1-3]. The wavelength of 2μm is strongly absorbed by water present in soft organic tissues, thereby providing constant speed of cutting and vaporization (i.e. “vaporesection”) regardless of vascularization, with high degree of control on the penetration depth (0.2-0.4mm) to reduce the risk of inadvertent deep injury. However, no study has yet reported its use for achieving hemostasis in the luminal gastrointestinal (GI) tract.

Aims & Methods: We conducted a pilot study in an established animal model to test for the first time the safety and efficacy of the Thulium Laser system (Cyber TM®, Quanta System, Varese, Italy) for hemostatic treatment in luminal GI-endoscopy. Therefore, various optical fibers (365 and 550 um) were evaluated with different power settings (10, 15, 20, and 25 watts), and diverse configurations (continued laser shaping or pulse modality). Study endpoint was to assess the impact of the device in terms of depth penetration and lateral tissue damage under a laser exposure prolonged for 3, 5 and 7 seconds at fixed distance (0.5-1 cm) from the mucosal surface. Results were compared to the effect of Argon Plasma Coagulation (APC) generated by an established standard electrosurgery system for hemostatic therapy in the luminal GI-tract with a 2.3 mm catheter using 20, 40 and 60 watts. All procedures were performed using a standard video-gastroscope and digitally recorded. Histopathological analysis based on the whole stomach were performed by an expert GI pathologist.

Results: Neither transmural perforation, nor any muscular layer damage was observed with both systems used. A progressive penetration depth and tissue damage was observed with increased laser power and APC settings, as well as with prolonged tissue exposure. Nonetheless, both the fiber diameter and the configuration modality of the laser system were found to have no impact on depth penetration and tissue damage, with only marginal effect on the lateral spread of vaporization. Overall, the laser system has been correlated with comparable degree of vertical tissue injury (from 0.1 to 2.0 mm), with a much more precise effect on target according to a lower lateral spreading damage (0.1-0.3mm and 0.2-0.7mm using the 365 and 550um fiber, respectively) compared to APC (1.1-1.6 mm).

Conclusion: The Thulium laser system appears to be safe and effective for hemostatic therapy in an ex vivo animal model of the upper GI-tract. In vivo studies should now confirm these initial results in a prospective setting.

Disclosure of Interest: None declared

P0141 ENDOSCOPIC PREDICTION OF RECURRENCE IN PATIENTS WITH EARLY GASTRIC CANCER AFTER MARGIN-NEGATIVE ENDOSCOPIC RESECTION: IS FOLLOW- UP BIOPSY NECESSARY AT ENDOSCOPIC RESECTION SCAR AFTER MARGIN-NEGATIVE RESECTION?

H. K. Na¹, K. D. Choi¹, J. Y. Ahn¹, J. H. Lee¹, D. H. Kim¹, H. J. Song¹, G. H. Lee¹, H.-Y. Jung¹, J.-H. Kim¹

¹Gastroenterology, Asan Medical Center, Seoul, Republic of Korea

Contact E-mail Address: hkna77@naver.com

Introduction: Although follow-up endosocpy is routinely performed after endoscopic resection for early gastric cancer (EGC), it has not been determined which endoscopic findings are suggestive of recurrence and when we take a biopsy at resection scar.

Aims & Methods: We aimed this study to predict local recurrence at resection scar with endoscopic criteria after margin-negative resection of EGC and to determined the necessity of follow-up biopsy at resection site.

Among 3037 cases of margin-negative endoscopic resection (including endoscopic mucosal resection and endoscopic submucosal dissection) for EGC between June 1995 and December 2011, a consecutive 22 patients with recurrent carcinoma at the site of endoscopic resection were identified. For each case, 4 controls were matched by age, sex and resectability (en-bloc or piecemeal). Endoscopic review was performed by consensus of 2 endoscopists based on the characteristic endoscopic criteria categorized as gross morphology (evenly elevated, unevenly elevated and flat), hyperemic change, mucosal defect (erosion or ulcer) and spontaneous bleeding.

Results: The mean age was 63.8 years and male was 72.9%. En-bloc resection was achieved in 100/110 (90.9%) cases. The mean interval between endoscopic resection and the diagnosis of recurrence was 16.8 months. Using endoscopic criteria of ‘elevated gross morphology (both evenly and unevenly) or hyperaemic change at resection scar, the sensitivity, specificity, and positive and negative predictive values of recurrence rate at resection site were 95.5%, 68.2%, 2.6% and 99.94%, respectively. When applying these criteria to histologically differentiated and en-bloc resected EGCs, the values were 100%, 71.4%, 3.0% and 100%, respectively.

Conclusion: Recurrence at endoscopic resection scar after margin negative resection of EGC is very rare. Routine follow-up biopsies may be unnecessary when the follow-up endoscopy shows flat mucosa without hyperaemic changes at the scar especially, for the en-bloc resected and differentiated EGCs.

Disclosure of Interest: None declared

P0142 FIRST STUDY ON A NEW THERAPEUTIC LASER SYSTEM FOR PER-ORAL ENDOSCOPIC MYOTOMY IN AN EX VIVO ANIMAL MODEL

H. Neumann¹, G. E. Tontini², L. Carmignani³, B. Bruni⁴, P. Soriani², L. Pastorelli²⁵, F. Fagnani⁶, C. Clemente⁴, M. Bottani², M. Vecchi²⁵

¹Department of Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany, ²Gastroenterology and Digestive Endoscopy Unit, ³Academic Urology Department, ⁴Pathology and Citodiagnostic Unit, IRCCS Policlinico San Donato, ⁵Department of Biomedical Sciences for Health, University of Milan, Milano, ⁶Surgical Division, Quanta System SpA, Varese, Italy

Contact E-mail Address: gianeugeniotontini@libero.it

Introduction: Therapeutic laser systems are established for surgical and endourlogical interventions [1-2]. Most recently, a new therapeutic laser system with a wavelength of 2μm has been developed to provide constant speed of cutting and vaporization (i.e. “vaporesection”) with a precise control on depth and lateral tissue penetration to avoid inadvertent injury. To date, no study has assessed the efficacy of the new device for luminal gastrointestinal endoscopy.

Aims & Methods: We conducted the first pilot study to test the feasibility of the newly introduced Thulium laser system (Cyber TM®, Quanta System, Varese, Italy) for POEM by using an established experimental setting (EASIE model). The POEM procedure was performed in standard technique. All steps were performed just by using the new Laser system. Subsequent to the endoscopic procedure, specimens were evaluated by an expert pathologist.

Results: A complete POEM by using the Thulium laser took approximately 20 minutes. No perforation to the luminal side (i.e. mucosal) occurred. For laser power settings the most effective choice was 25-35 watts for mucosal excision and 15-25 watts for submucosal and muscular excision. Histopathology confirmed a clean and safe cutting of the different layers.

Conclusion: This is the first study of the newly introduced Thulium laser system showing the safety and efficacy of the new device for performing POEM procedures. These initial results should now be confirmed in additional in vivo studies.

Disclosure of Interest: None declared

P0143 EFFICACY AND LEARNING CURVE OF A NEW SCISSOR-LIKE DEVICE FOR ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD)

H. Neumann¹, S. Löffler¹, M. Neurath¹, A. Nägel¹

¹Department of Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany

Contact E-mail Address: helmut.neumann@uk-erlangen.de

Introduction: ESD has become the standard technique for early cancerous lesions, particularly in Asian countries. However, current limitations of ESD include the complication rate, a distinct learning curve and the need of various devices, resulting in substantial costs of the procedure.

Aims & Methods: Aim was to prospectively assess the efficacy and learning curve of a new alligator scissor-like device for ESD. Accordingly, a prospective ex vivo study was performed in an established experimental setting. Ex vivo porcine models were utilized in the EASIE endoscopic simulator of interventional endoscopy. First, artificial lesions, each 2x2 cm in size, were created in fresh ex vivo porcine stomachs at the fundus, corpus and antrum. Two beginners with less than 10 ESD procedures each participated in the study. All study parameters were independently recorded. ESD was performed after marking of the lesions with the closed ESD-instrument, followed by lifting of the mucosa with submucosal injection of saline. Afterwards, circumferential incision of the lesions was performed with the new ESD-instrument. For resection, the submucosa was grasped with the scissor-like device, elevated and cut. Resection specimens were retrieved to evaluate if all marks were included (R0).

Results: Average size of removed lesions was 35 mm. En-bloc resection rate was 100% and R0 resection rate was 86%. After the initial three cases, R0 resection was achieved in all cases. The total procedure time improved significantly during the study (52.4 minutes versus 21.10 minutes; p < 0.05). One perforation occurred which could be managed with endoclips. Endoscopists satisfaction was high throughout all cases.

Conclusion: The new scissor-like device for ESD appears to be a safe and efficient new instrument for ESD which can relatively easy being learned. Further studies should now focus on in vivo studies to confirm these initial results.

Disclosure of Interest: None declared

P0144 CAPNOGRAPHY DURING SEDATION FOR ENDOSCOPIC TREATMENT USING CARBON DIOXIDE SUPPLY SYSTEM

H. Takamaru¹, Y. Kawaguchi², I. Oda¹, M. Sekiguchi¹, S. Abe¹, S. Nonaka¹, H. Suzuki¹, S. Yoshinaga¹, Y. Saito¹

¹Endoscopy Division, ²Anesthesiology and Critical Care Medicine, National Cancer Center Hospital, Tokyo, Japan

Contact E-mail Address: h.takamaru@gmail.com

Introduction: A respiratory monitoring during sedation for endoscopy has an important role. Pulse oximetry is one of the most common ways for respiratory monitoring, however, unexpected adverse effect may occur with pulse oximetry only. In the cases of deep sedation, visual examination, auscultation and monitoring by capnography may be recommended. However, only few studies reported about the capnography during sedation for endoscopic treatment of lesions located in upper gastrointestinal tract using endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR) technique, with deep sedation and carbon dioxide supply system.

Aims & Methods: The aim of this study is to evaluate the stability of respiratory monitoring by capnography during deep sedation for ESD/EMR using carbon dioxide supply system.

Twenty-six patients with successfully monitored both capnography and respiratory monitoring system by breath sounds (Rad87^®, Masimo, Japan) among 52 consecutive patients who underwent endoscopic treatment (ESD/EMR) under deep sedation without intubation by anesthesiologist from December 2013 to October 2014 were analyzed. Oxygen saturation (SpO₂) was measured by pulse oximetry. Respiratory rate per minute (RR) was measured by side stream capnography and recorded every 8 seconds. RR was also measured from breath sounds by Rad-87^® as gold standard and recorded every 2 seconds. We compared the average value of RR for every 8 seconds with RR by capnography and calculated Pearson's correlation coefficient. We also defined “outlier” when the value of RR by capnography was more or less than RR range of ±50% by Rad87^®.

Results: In this study, 23 of 26 patients were male and median age was 72.5 years old (IQR: 62.5-80.0). Mean BMI was 22.1(±4.5). Patients who had cardiovascular or pulmonary disease were 26.9% and 19.2%, respectively. Location where patients had the lesions was follows; 17 patients have lesions in esophagus, 5 patients in normal stomach, 2 patients in gastric tube, one patient in gastric remnant. Mean size of the resected specimens was 39.3mm (± 8.8mm). Median time of procedure is 126 minutes (IQR: 91.5 – 167.8 min). Anesthesiologist used fentanyl and propofol for all patients. Mean amount of total administered agent is 0.14mg and 1220mg, respectively. The average of SpO₂, RR by Rad87^® and RR by capnography during procedure was 97.6%, 9.6/min and 13.8, respectively. Four cases showed transient hypoxia (SpO2 < 90%). One of four cases showed hypoxemia for few minute, and this adverse effect could be detected by capnography as apnea before pulse oximetry detection. One case showed relatively strong correlation (r=0.511), and three cases showed weak correlation (0.2 < r < 0.4), while other 22 cases showed no correlation between RR measured by capnography and by Rad87^®. Median frequency of outlier for RR by capnograhpy was 35.2% (IQR: 26.5 – 48.8%).

Conclusion: Respiratory monitoring by capnography during deep sedation for endoscopic treatment with carbon dioxide supply system may be unstable and need some improvement in some situation.

Disclosure of Interest: None declared

P0145 THREAD TRACTION WITH A SHEATH OF POLYPECTOMY SNARE FACILITATES ENDOSCOPIC SUBMUCOSAL DISSECTION OF EARLY GASTRIC CANCERS

H. Noda¹, N. Ogasawara¹, A. Koshino¹, S. Fukuta¹, T. Sugiyama¹, S. Noguchi¹, K. Adachi¹, T. Yoshimine¹, Y. Yamaguchi¹, Y. Kondo¹, Y. Ito¹, S. Izawa¹, M. Ebi¹, Y. Funaki¹, M. Sasaki¹, K. Kasugai¹

¹Gastroenterology, Aichi Medical University School of Medicine, Nagakute, Japan

Contact E-mail Address: bisaipan@aichi-med-u.ac.jp

Introduction: Endoscopic submucosal dissection (ESD) has been established as a standard therapy for early gastric neoplasms. During ESD, the mobility of the lesion increases as submucosal dissection proceeds and it becomes difficult to attain effective counter traction. To overcome this problem, various traction methods have been developed. Recently, the thread-traction (TT) method has been developed. However, in TT method, the movement of the thread was interfered with the movement of the endoscopy, and it resulted in disturbing to make the appropriate traction which the operator required. Moreover, in TT method, the lesion can be pulled only to the mouth side but not to the anal side by the thread. Therefore, we modified TT method and developed novel TT method using a sheath of polypectomy snare (TTSPS) method. The TTSPS method enabled the comfortable ESD procedure that did not disturb the thread movement without the interference with the endoscopy and could pull the lesion towards not only to the oral side but also to the anal side regardless of lesion locations.

Aims & Methods: This study aimed to evaluate usefulness of TTSPS method during ESD. Thirty-four consecutive patients who underwent conventional ESD between May 2013 and December 2013 and 54 consecutive patients who underwent ESD with the TTSPS method between January 2014 and March 2015 were included in the study. We compared counter traction ESD with the TTSPS method and conventional ESD that did not involve the new traction system in terms of the duration, the number of times regarding the arterial bleeding and the times regarding the local injection all after completion of circumferential mucosal incision until completion of dissection of the specimen.

Results: The median dissection duration after completion of circumferential mucosal incision until completion of dissection of the specimen for all lesions significantly differed between conventional ESD and ESD with method [conventional ESD, 90 min (range 30-320 min) vs ESD with TTSPS method, 60 min (range 15-160 min); p=0.015]. The median number of times regarding the arterial bleeding after completion of circumferential mucosal incision until completion of dissection of the specimen was significantly less in ESD with TTSPS method than in conventional ESD [conventional ESD, 3 times (range 0-25) vs ESD with TTSPS method, 2 times (range 0-7) ; p=0.015]. The median number of times regarding the local injection after completion of circumferential mucosal incision until completion of dissection of the specimen significantly differed between the two groups [conventional ESD 10 times (range 3-51), vs ESD with TTSPS method, 8 times (range 1-27) p=0.04]. There was no significant difference in complications between conventional ESD and ESD with TTSPS method.

Conclusion: Our study suggests that TTSPS method is straightforward, safe, easy, noninvasive, cost-effective and uses readily available instruments to enhance visualization of cutting lines. Our TTSPS method can be universally applied to conventional ESD.

Disclosure of Interest: None declared

P0146 DEVELOPMENT OF A NOVEL ENDOSCOPIC SUTURING DEVICE USING NEW RECIPROCATING CURVED NEEDLE: AN EX VIVO COMPARISON STUDY

H. S. Choi¹, H. J. Chun¹, I. K. Yoo¹, J. M. Lee¹, S. H. Kim¹, E. S. Kim¹, B. Keum¹, Y. T. Jeen¹, H. S. Lee², C. D. Kim², J. J. Park², S. W. Lee², S. Yoon³, S.-H. Park³, Y. Kim³, B. Kim³, Y. Song³, D. Hong³

¹Internal Medicine, Institute of Gastrointestinal Medical Instrument Research, Korea University College of Medicine, ²Internal Medicine, Korea University College of Medicine, ³Division of Mechanical Engineering, Korea University, Seoul, Republic of Korea

Contact E-mail Address: mdkorea@gmail.com

Introduction: Endoscopic Suturing Device has been developing rapidly for not only Natural orifice transluminal endoscopic surgery (NOTES) but also minimally invasive obesity treatment. However, some issues remain involving the complex approach to the suturing site and the many additional instruments required that render the procedure more difficult. The complex suturing mechanism and tools not only increase the operation time but also decrease the feasibility of minimally invasive surgery. The authors have developed a novel endoscopic suturing devices to continuously suture a viscerotomy of stomach to overcome limitations of previous suturing devices.

Aims & Methods: The goal of this study is to develop an endoscopic suturing device and to demonstrate the feasibility of the device by showing the strength of closure. New endoscopic suture device is composed of main body, suturing-arms, curved needle, protective tube, and control device. This endoscopic closer (EN-closer) device sutures wound with a curved needle using back and forth movement. The endoscopic suturing device with new closure mechanism was compared with two other closure techniques; endoscopic clips and hand-sewn in porcine stomach. After closure, air leakage pressure was used to determine the strength of the perforation closure by an automated pressure gauge.

Results: After the mechanism design and implementation, we carried out a feasibility study on 10 porcine stomach models. In a comparative experiment, each endoscopic clip (endoclip) method and full-thickness stitches involved hand suturing was used 10 times to increase reliability. The average leakage pressure for the En-closer was 43.25mmHg. The average closer strength of the En-closer does not significantly differ from that of the endoclip, but standard deviation of the En-closer is significantly smaller than that of the endoclip treated stomachs. The En-closer that is capable of multiple stitches with a single endoscope insertion had similar closure strength to that of the endoclips but showed a more consistent sequence than the endoclips.

Conclusion: New suture device competently produced a tight, reliable, and consistent closure. Our instrument platform could be an important basis for future developments of not only gastric NOTES devices but also endoscopic bariatric surgery device. This research showed a new approach for endoscopic suturing devices.

Disclosure of Interest: None declared

P0147 WHEN SHOULD WE USE HEMOSPRAY? A SINGLE CENTRE EXPERIENCE

I. Nasr¹, S. De Martino¹, D.-M. Borrow², J. M. Dunn¹

¹Gastroenterology, ²Gastroenteroloy, Guys and St Thomas' NHS Trust, London, United Kingdom

Contact E-mail Address: ikram.nasr@gstt.nhs.uk

Introduction: Hemospray is an inorganic nanopowder produced by Cook Medical and is licensed in Europe and Canada for the management of nonvariceal upper gastrointestinal bleed (NVUGIB). The powder adheres to liquid and forms a coagulum which concentrates clotting factors and stimulates the internal clotting cascade. There are numerous reports of successful haemostasis with hemospray, some reporting success rates of 85%[i]. However, the knowledge of which lesion is most suitable for hemospray use remains unclear. We report our experience at Guys and St Thomas’ NHS trust to establish the lesions most likely to benefit from hemospray either as a primary intervention or an add-on strategy.

Aims & Methods: A retrospective review of endoscopic procedures that required hemospray was performed and the data was extracted from our endoscopy reporting system between December 2013 and February 2015 (14 months). We identified 32 patients who received hemospray, and excluded 2 where hemospray was applied blindly and the bleeding lesion was missed. The primary outcome was achieving primary haemostasis. Cases of recurrent GI bleed requiring further endoscopic or radiological intervention within 72 hours were considered unsuccessful.

Results: The 30 procedures were divided according to the procedure performed.

1. Procedure induced bleeding: 9/30 (7 post Barrett’s endoscopic mucosal resection (EMR), 1 post gastric polypectomy and 1 iatrogenic bleed post nasojejunal tube insertion).

2. NVUGIB: 17/30

3. Enteroscopy small bowel bleed: 2/30

4. Colonoscopy: 2/30

Primary haemostasis was achieved in 77%, of which 7% required further endoscopic procedure or interventional radiological intervention within 72 hours (Table). The coagulum was not seen on second endoscopy.

Abstract number: P0147

Results of hemospray use
	Procedure induced upper GI	Forrest 1a	Forrest 1b	Forrest 2a	Forrest 2b	Distal ileum (Enteroscopy)	Colonic bleed
Primary haemostasis achieved and sustained	9	0	5	2	3	1	1
Haemostasis not sustained	0	2	5	0	0	1	0
Unsuccessful	0	4	1	0	0	1	1

Conclusion: Hemospray provides good hemostasis for post procedure, in particular post EMR bleed, as a single agent or where coagulation alone failed. Bleeding from Forrest 1b, 2a and 2b responded well to hemospray as a second modality, or single modality when the lesion was inaccessible. Forrest 1a had a poor response to hemospray and all cases required further endotherapy or interventional radiology. Further evidence is required to establish the value of hemospray in colonic and variceal bleed.

Disclosure of Interest: None declared

P0149 ENDOSCOPIC MANAGEMENT OF POST-OPERATIVE LEAKAGES AND FISTULAS AFTER ESOPHAGEAL ONCOLOGIC SURGERY: EVALUATION OF EFFICACY IN A LARGE RETROSPECTIVE STUDY

C. Servajean¹, J.-M. Gonzalez¹, M. Gasmi¹, B. X. D'Journo², J.-C. Grimaud¹, M. Barthet¹

¹Gastroenterology, ²Thoracic Surgery, AP-HM, North Hospital, Marseille, France

Contact E-mail Address: jmgonza05@yahoo.fr

Introduction: Anastomotic leakages or fistulas are among the most common and severe complications of esophagectomy for esophageal cancer, with high grade of mortality. Recently the endoscopic management has taken a growing place in the treatment of digestive post-operative complications (1). The aim of this study was to evaluate the effectiveness and the characteristics of the endoscopic management in this indication.

Aims & Methods: This is a monocentric study on consecutive patients treated surgically in our institution between 2010 and 2014 for esophageal carcinomas. During this period, on 126 patients operated, 35 developed post-operative fistulas or leakages (27%), endoscopically managed and included in this study. All the procedures were performed in our endoscopy unit, by interventional endoscopists, in intubated patients under general anesthesia, using a large operating channel gastroscope (3.8mm, Pentax, Japan) and fluoroscopy. The patients were systematically controlled endoscopically 6 weeks after the endoscopic treatment to check the efficacy out and to evaluate the need for an additional treatment. The primary or secondary efficacy, the time between surgery, diagnostic and endoscopy, the number of procedures, the material used (stents, clips, or drains), the complications, and the death rate were recorded, and uni- and multivariate analysis was carried out to determine predictive factors of success.

Results: There were 4 women and 31 men, with a median age of 61.7 years ± 8.9 [43-85]. The surgical techniques were in majority Lewis-Santi for 48.6% of cases, Akiyama for 45.7%. 71.4% patients have undergone neo-adjuvant chemo radiation therapy and 77.1% were hospitalized in intensive care unit. The median delay between surgery and first endoscopy was 8.5 days [6.00-18.25]. 88% of the patients were treated using metallic (double type) esophageal stents, with a removability rate of 100% and a migration rate of 18%. The other ones were treated by Over-the-scope clips, naso-cystic drain or combined approach. The mean number of endoscopy per patient was 2.6 ± 1.57 [1-10], with a mean number of 1.6 ± 1.35 [0-7] stents placed. The primary efficacy of the endoscopic treatment was 48.6%, the final efficacy was 68.6%. The mortality rate in patients endoscopically managed was 17%, none being related to procedures. No predictive risk factor of success or failure of the endoscopic treatment (CRT, type of surgery, fistula size, age…) could be identified in univariate as well as in multivariate analysis.

Conclusion: The endoscopic management of leakages or fistulas after esophageal surgery is feasible, and lead to an overall effectiveness rate of 68.8%. There were no significant complications related to the procedures, and the mortality rate was decreased to 17% compared to 40 to 100% rate in the literature (2). Self-expandable metallic stents are the most common used treatment with a removability rate of 100% and a migration rate of 18%.

Disclosure of Interest: None declared

P0150 CONFOCAL LASER ENDOMICROSCOPY IMAGING OF NEOANGIOGENESIS USING FITC-CD105 ANTIBODIES IN COLORECTAL CANCER: HUMAN IN VIVO TESTING

A. Ciocalteu¹, T. Cartana¹, D. Pirici², C. Georgescu³, I. Cherciu¹, C. Cristea¹⁴, A. Saftoiu¹⁵

¹Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, ²Department of Research Methodology, University of Medicine and Pharmacy of Craiova, ³Department of Pathology, Emergency County Hospital Craiova, Craiova, Romania, ⁴Hepato-gastroenterologie, Hopital Antoine Beclere, Clamart, Ile de France, France, ⁵Gastrointestinal Unit, Copenhagen University Hospital Herlev, Copenhagen, Denmark

Introduction: To date, the determination of neoangiogenic status and its dynamic assessment in real time has been challenging and, therefore, has made treatment optimization in colorectal cancers difficult. One strategy for antiangiogenic therapy is the long-term suppression of forming new blood vessels. Recent developments in endoscopic imaging technologies such as confocal laser endomicroscopy (CLE) have contributed to the progress from macroscopic evaluation to ex vivo molecular experiments and consequently to promising in vivo imaging by using fluorescently labeled antibodies.

Aims & Methods: The aim of this study was to evaluate the feasibility of in vivo acquisition of microscopic images using fluorescent CD105 antibodies for molecular imaging in human colorectal cancer. The current approach builds on our previous study in which we proposed ex vivo CLE examination and CD105 immunostaining of fresh tissue samples as a more reliable tool for evaluation of neoangiogenesis in rectal cancer [1]. Tumor was washed with saline solution and it was evaluated from a stable position using an eCLE system, before undergoing surgery. After excluding the presence of tissue autofluorescence, 1 ml fluorescent antibody solution (FITC-labeled anti-CD105/Endoglin antibody, Exbio, 1:5) was topically administered through a spray-catheter. After 10 min of incubation, the targeted area was analyzed by CLE and images were recorded. The fractal dimension of tumor vessels was calculated offline using “fractal box count” tool in Image J software. Grid method was applied to determine the vessel density. Before in vivo testing, multiple attempts were made at establishing the optimal antibody-tissue contact time using paraffin-embedded tissue sections under fluorescence microscopy conditions. Immunohistochemistry staining with CD105 was used as a gold standard.

Results: In vivo CLE analysis of CD105 expression in human colorectal cancer enabled the study of vascular network, revealing a chaotic structure. Both good and medium quality images were eligible for clinical analysis. Fractal value was 1.57, indicating the chaotic architecture (with 2 being the fractal value for normal vessels). Average vessel density was 46.09± 7.06 vessels/mm².

Conclusion: In vivo molecular imaging of human colorectal cancer neoangiogenesis using CLE and FITC-CD105 antibodies is feasible. Future in vivo applications of immunoendoscopy using CD105 could provide a more specific analysis of tumor microvascular architecture in order to improve diagnosis, patient stratification and monitoring of antiangiogenic therapy.

Disclosure of Interest: None declared

P0151 THE EFFECTIVENESS OF A CUSTOMIZED MOBILE APPLICATION IN COLONOSCOPY PREPARATION: A RANDOMIZED CONTROLLED TRIAL

A. I. Sharara¹, J. M. Chalhoub¹, M. Beydoun¹, A. H. Harb¹, H. Chehab¹, Z. D. El Reda¹, F. H. Mourad¹, F. S. Sarkis¹

¹Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon

Contact E-mail Address: as08@aub.edu.lb

Introduction: Colonoscopy preparations are generally poorly tolerated. Compliance with dietary instructions and proper use of the prescribed purgative solution are essential in achieving an adequate bowel preparation.

Aims & Methods: The study aims at assessing the effect of a customized mobile application (with dietary instructions, illustrations, reminders and push notifications) on the compliance and adherence to instructions and diet and consequently on the quality of bowel cleansing.

Consecutive patients scheduled for elective colonoscopy and having on-hand personal smartphones were randomly assigned to one of two groups. The first group (Paper) received face-to-face detailed paper instructions while the second group (App) received the same paper instructions and had the customized application downloaded onto their phone including the scheduled date and time of their colonoscopy appointment. The preparation consisted of split-dose sodium picosulfate/magnesium citrate (SPS) (Picoprep®, Ferring, Saint-Prex, Switzerland) and a 3-day diet consisting of a low-fiber diet for the first 2 days, and a clear fluid diet on the last day before colonoscopy (day -1). The first dose of SPS was to be taken the eve prior to colonoscopy, and the second dose a minimum of 4 hours before the procedure. Colonoscopy appointments were scheduled between 10 am and 3 pm. Patients were interviewed prior to colonoscopy about compliance with the 3-day diet and use of the SPS solution as well as their assessment of the preparation and the provided instructions. The colonoscopist, blinded to assignment, was asked to grade the bowel cleanliness after the examination using the Aronchick, Ottawa, and Chicago bowel scales. The primary endpoint was overall compliance with dietary and purgative solution instructions. Quality of the preparation was a secondary endpoint.

Results: 160 patients were enrolled (80 in each arm). The average age was 54 (SD = 13), 55.6% were males, and 27.5% of patients had a BMI of ≥30. No difference in overall patient compliance and bowel cleanliness (on all 3 scales) was observed between the Paper and App groups. An adequate bowel preparation defined as either excellent or good on the Aronchick scale was noted in 82.5% and 77.2% of Paper vs. App group respectively (p=0.68). Gender, age, BMI, and time of colonoscopy (am vs. pm) did not influence bowel cleanliness or patient compliance. Full compliance with clear fluids on day -1 was seen in 93.9% of patients with a BMI < 30 vs. 77.3% of those with a BMI ≥ 30 (p=0.009). SPS was very well tolerated by 81.9% of patients as evidenced by their willingness to use it again in the future. The application was deemed user-friendly and helpful/indispensable by 96.2% and 87.3% of patients in the App group respectively.

Conclusion: Split-dose sodium picosulfate with dietary modification is well tolerated and highly effective for bowel cleaning prior to elective colonoscopy. A detailed face-to-face explanation of bowel preparation instructions leads to comparable results regardless of the instruction method used. Customized smartphone applications may replace traditional paper instructions in this information technology era.

Clinicaltrials.gov identifier: NCT02410720

Disclosure of Interest: A. Sharara Financial support for research: Supported by an investigator-initiated grant from Ferring, J. Chalhoub: None declared, M. Beydoun: None declared, A. Harb: None declared, H. Chehab: None declared, Z. El Reda: None declared, F. Mourad: None declared, F. Sarkis: None declared

P0152 EARLY AND LONG-TERM OUTCOME OF A SINGLE-CENTER DATABASE ON ESD FOR COLORECTAL LESIONS WITH SPECIAL EMPHASIS ON LEARNING CURVE IN WESTERN SETTING

A. Murino¹, E. Ferrara¹, C. Ciscato¹, S. Carrara¹, C. Hassan², I. Bravatà¹, A. Loriga¹, S. Sferrazza¹, A. Anderloni¹, A. Repici¹

¹Digestive Endoscopy Unit. Division of Gastroenterology, Humanitas Research Hospital, Rozzano, Milano, ²Department of Gastroenterology, Nuova Regina Margherita, Rome, Italy

Contact E-mail Address: albertomurino@yahoo.it

Introduction: ESD for colorectal lesion is well established in Japan while has limited application in western countries.

Aims & Methods: The aim of present study was to report the early and long-term outcome as well the learning curve of a tertiary referral center that has established a database for colorectal ESD since 2008. Information on all patients who underwent ESD for colorectal lesions at our institution since 2008 have been prospectively collected in a database and patients followed-up with endoscopy on regular basis according to the lesion histology and standard guidelines. Collected data included size, morphology, location, technique of ESD, en-bloc rate, R0 rate, complication and recurrence. Part of these data have been previously reported in 2 papers. Results were compared between three consecutive study periods (2 years each until end of 2014) in order to determine the effect of learning curve on outcome.

Results: Overall data on 286 patients (167M, mean age 68.3 y) were recorded in the data base. Lesions were located in the rectum in 187 cases (68.8%) and mean diameter was 3.9 mm (range 15 to 110). ESD was aborted because of technical difficulties in 29 (10.1) with 12 of these patients switched to multipiece EMR and 17 referred for surgery. Hybdrid-knife technology was used in 105 cases (36%) while different types of knife (Flush-knife, Hook-knife, Dual-knife and Flex-knife) have been used in the remaining cases. Median operative time 108 minutes. En-bloc resection and R0 resection were respectively 82% (235 out of 286) and 72% (208 out of 286). Perforation occurred in 20 patients (6.9%) while bleeding occurred in 7 (2.4%) with all bleeding cases successfully treated with conservative management in 2 cases or endoscopic intervention in 5. Perforation required surgery in 7 cases while was managed conservatively in the remaining. No mortality associated to the procedure was observed. Histology has demonstrated intramucosal cancer or submucosal cancer in 110 cases (38.4%) and surgery was required because of advanced histology in 26 patients (9%). The mean follow-up was 32.7 months with 11 patients lost during follow-up and 4 patients died because of unrelated disease. The overall recurrence rate was 6.2% with most of these patients successfully treated with additional endoscopic therapy and 2 patients requiring surgery. Mean operation time (152 minutes vs 88 minutes, p=0.001), en-bloc resection (62% to 92%, p=0.05), R0 (56% to 85%, p=0.001) significantly improve from period 1 (2008-2010) to period 3 (2012-2014). Perforation rate decreased from 11% in period 1 to 6.5% even though did not reach the statistical significance.

Conclusion: Data coming from a single European center experience confirm that ESD for colorectal lesions can be safely and effectively performed in western setting. However a long-training period with progressive learning curve is required to obtain results comparable with Japanese experts in terms of efficacy and perforation rate.

Disclosure of Interest: None declared

P0153 NON-ANESTHESIOLOGIST ADMINISTERED PROPOFOL SEDATION IN COLONOSCOPY – RESULTS OF A RANDOMIZED CONTROLLED TRIAL

A. O. Ferreira¹, J. Torres¹, E. Barjas¹, J. Nunes¹, L. Glória¹, C. Fidalgo¹, R. Ferreira¹, S. Pereira², M. Rocha², S. Dias¹, A. A. Santos¹, M. Cravo¹

¹Gastroenterology, ²Hospital Beatriz Ângelo, Lisboa, Portugal

Contact E-mail Address: alex.gastrohep@gmail.com

Introduction: Propofol allows the best sedation in colonoscopy. There is only one Randomized Controlled Trial (RCT) comparing Non-Anesthesiologist Administered Propofol Sedation (NAAPS) to sedation by an anesthesiologist.

Aims & Methods: Our goal was to compare the incidence of sedation related adverse events (AE), colonoscopy quality and patient satisfaction between NAAPS and anesthesiologist sedation. We performed a single blinded RCT with two parallel intervention groups (group A – NAAPS; group B – anesthesiologist sedation). The primary endpoint was the incidence of AE as defined by the World SIVA International Task Force on Sedation. Secondary endpoints were propofol dose, patient satisfaction and pain assessed by a 10 point visual analogue scale, procedure and recovery time and colonoscopy quality indicators (cecal intubation rate, withdrawal time, adenoma detection rate). Based on the AE incidence of our preliminary experience a sample size of 320 (1:1) was calculated with a non-inferiority margin of 15% for a power of 90% at a 5% level of significance. Patients aged 18-80 with low anesthetic risk (ASA I-II) were included. Statistical analysis was performed with SPSS version 21. Chi-square, Fischer’s exact, t-tests and logistic regression were used as indicated.

Results: A total of 277 colonoscopies were performed (table 1). The incidence of AE was 39.3% on group A and 39.0% on group B (OR1.013; IC95% 0.622-1.651; p=0.959). There were no severe (sentinel) AE events. The following interventions were necessary: atropine administration (0% vs 5.5%; p=0.004); airway repositioning (8.7% vs 4.7%; p=0.196); increase in O2 administration (6.7% vs 4.2%; p=0.317); increase in fluids rate (2.6% vs 0.8%; p=0.242). Mean propofol dose: group A 215 ± 92 mg vs group B 230 ± 97 mg (p=0.205). Procedure times was 21.59 ± 12.967 and 18.64 ± 9.859 min (p=0.033), withdrawal time was 11.37 ± 9.839 vs 9.84 ± 7.509 min (p=0.154) and recovery time was 58 ± 33 min vs 67 ± 29 min (p=0.032). Patients had no pain (0) in 83.5% vs 88.9% (p=0.208) and reported complete satisfaction with the sedation in 82.4% vs 85.1% (p=0.887). Procedural amnesia was reported in 83.9% vs 90.8% (p=0.093). All but 2 patients (group B) were willing to repeat the colonoscopy under propofol sedation. Cecal intubation rates were 94.7% vs 96.1% (p=0.584), adenoma detection rates were 28.4% vs 23.2% (p=0.331).

	Group A (n=150)	Group B (n=127)
Male sex, n(%)	61 (40.7)	50 (39.4)
Mean age, years(sd)	58.6 (13.8)	55.4 (15.4)
ASA I/II, n	13/137	18/107
Cardiovascular disease, n(%)	20 (13.4)	12 (10.4)
Smoking, n(%)	24 (18.0)	20 (17.5)
Snoring history, n(%)	17 (13.1)	24 (21.8)

Conclusion: NAAPS is equivalent to anesthesiologist sedation in the rate of adverse events in a low risk population. Clinicaltrials.gov (NCT02067065).

Disclosure of Interest: None declared

P0154 IS THERE A RELATION BETWEEN BOSTON BOWEL PREPARATION SCALE AND THE DETECTION RATE OF POLYPS AT SCREENING COLONOSCOPY?

A. Popescu¹, I. Sporea¹, M. Popescu¹, T. Moga¹, C. Ivascu¹, R. Şirli¹, M. Dănilă¹, A. Damra¹

¹Gastroenterology and Hepatology, University of Medicine and Pharmacy Victor Babes Timisoara, Timisoara, Romania

Contact E-mail Address: alinamircea.popescu@gmail.com

Introduction: Colonoscopy is the most sensitive method for colorectal cancer screening, but inadequate bowel preparation can result in both missed pathological lesions and cancelled procedures.

Aims & Methods: We prospectively followed up the quality of colonic preparation at screening colonoscopy and tried to establish if there is a potential association between the bowel preparation and the polyp detection rate in screening colonoscopy.

We evaluated prospectively the bowel preparation during colonoscopy, using the Boston bowel preparation scale (BBPS) (a scoring system applied to the 3 broad regions of the colon: right colon, transverse colon and left colon, each part being evaluated from 0 and 3 as follows: 3 = entire mucosa of the segment seen well, 2 = minor amount of residual staining, 1 = segments not well seen due to residual stool or/and opaque liquid, 0 = unprepared segment), with a maximum of 9 points (perfectly cleaned colon). The bowel preparation was performed either with split or non-split regimens using PEG solution.

Results: We evaluated 2412 patients in whom screening colonoscopy was performed: 1377 women (57%) and 1035 men (43%). The mean BBPS score was 6.6 ± 1.3. Considering an excellent bowel preparation for the colonoscopy a BBPS score of 8 or 9 points, a good bowel preparation a BBPS score ≥7 points, and a score of ?5 points as an inadequate bowel preparation, we obtained the following BBPS score distribution: excellent preparation in 634 (26.3%) patients, good preparation in 1232 (51%) patients, and an inadequate preparation in 144 (6%) patients. In 450 (18.6%) patients we found one or more colonic polyps and in 166 (6.8%) patients significant polyps (polyp ≥1cm). We compared the polyp detection rate and significant polyp detection rate in relation with the BBPS score and we obtained the following results:

Abstract number: P0154

BBPS Score	8-9 (634 p) *	≥7 (1232 p) #	≥5 (2268 p) °	?5 (144 p)?
Number of cases with polyps	163 (25.7%)	219 (17.7%)	420 (18.5%)	30 (20.8%)	* vs. # p=0.0001* vs. ° p=0.0001* vs. ? p=0.2617# vs. ° p=0.5894# vs. ? p=0.4230° vs. ? p=0.5640
Significant polyps (polyp >1cm)	32 (5%)	73 (5.9%)	152 (6.7%)	12 (8.3%)	* vs. # p=0.4871* vs. ° p=0.1438* vs. ? p=0.1761# vs. ° p=0.3953# vs. ? p=0.3416° vs.? p=0.5693

Conclusion: The polyp detection rate increased with the increasing of BBPS score; for significant polyps this association was not found.

Disclosure of Interest: None declared

P0155 MARKED VARIATION IN ENDOSCOPIC MUCOSAL RESECTION OUTCOMES WITHIN THE UK BOWEL CANCER SCREENING PROGRAMME

A. Chattree ^1,2, J. Painter³, J. Silcock⁴, D. Nylander⁵, M. D. Rutter^1,2

¹Gastroenterology, North Tees and Hartlepool NHS Foundation Trust, Stockton on Tees, ²School of Health Sciences, University of Durham, Durham, ³Gastroenterology, Sunderland Royal Hospital, Sunderland, ⁴Gastroenterology, University Hospital of North Durham, Durham, ⁵Gastroenterology, Royal Victoria Infirmary, Newcastle Upon Tyne, United Kingdom

Contact E-mail Address: amitchattree@nhs.net

Introduction: The use of endoscopic mucosal resection (EMR) is established as first-line treatment for the treatment of large non-pedunculated colorectal polyps (LNPCP), with practice now widespread in both the district general and tertiary setting. A large proportion of LNPCPs in the UK are managed within the Bowel Cancer Screening Programme (BCSP)¹ and recent data demonstrating increased variation in endoscopic polypectomy outcomes with increased polyp size² has led to concerns that the quality of endoscopic LNPCP management also varies widely between BCSP clinicians and centres, irrespective of procedure volume, with many patients potentially subject to suboptimal therapy.

Aims & Methods: Retrospective analysis was conducted on LNPCPs [MDR1] managed using EMR in the England Bowel Cancer Screening Programme (BCSP) within the North East region between 2011-14. A comparison of 12 month recurrence, an internationally recognised marker of successful endotherapy³, was made between the four North East screening centres. Statistical analysis was performed using the Fisher’s exact test.

Results: A total of 135 lesions were subject to 12 month surveillance with recurrent/residual polyp (RRP) identified in 8.1% of cases. RRP incidence was 8.4%, 0%, 29.2% and 3.9% at the 4 screening centres respectively, with screening centre location strongly associated with the probability of a finding of unsuccessful endotherapy (p=0.001).

		12 month recurrence (%)		Total (n)
		n	y
Screening Centre	A	91.6	8.4	24
	B	100	0	36
	C	70.8	29.2	24
D	96.1	3.9	51
Total		91.9%	8.1%	135

Conclusion: A vast difference was demonstrated in the quality of endotherapy undertaken within a wide geographical area, with 12 month RRP varying between 0% and 29.2%. The results from this series are especially noteworthy given that the endoscopists concerned were all BCSP accredited, and therefore highly experienced and subject to a strict certification process. These findings indicate that advanced polypectomy is not a universal skill and that endoscopist quality varies markedly irrespective of experience. In addition, they highlight the importance of accurate lesion management and the identification of endoscopists with the requisite expertise to manage these complex lesions.

Disclosure of Interest: None declared

P0156 CAECAL LOCATION IS ASSOCIATED WITH INCREASED LESION RECURRENCE FOLLOWING ENDOSCOPIC MUCOSAL RESECTION OF LARGE NON-PEDUNCULATED COLORECTAL POLYPS

A. Chattree ^1,2, M. D. Rutter^1,2

¹Gastroenterology, North Tees and Hartlepool NHS Foundation Trust, Stockton on Tees, ²School of Health Sciences, University of Durham, Durham, United Kingdom

Contact E-mail Address: amitchattree@nhs.net

Introduction: Large caecal polyps over 2cm in size are considered amongst the most complex lesions to achieve successful endoscopic resection, with recent data suggesting a significantly increased risk of post procedure bleeding and perforation associated with their endoscopic removal compared with elsewhere in the colon.^1,2 There is however a paucity of data assessing whether caecal location affects successful (R₀) clearance of lesions.

Aims & Methods: Retrospective analysis was conducted on large non-pedunculated colorectal polyps (LNPCPs) managed with endoscopic mucosal resection in the English Bowel Cancer Screening Programme (BCSP) between 2011-14. A comparison of 12 month recurrence rates, an internationally recognised marker of treatment success,³ was made between caecal and non-caecal LNPCP groups. Statistical analysis was performed using the chi-squared test.

Results: A total of 135 lesions were identified, with 12 month recurrence identified in 8.1% of cases. Caecal location demonstrated a strongly significant association with recurrence compared with non-caecal location (27.8% vs 5.1%, p=0.007)

		12 month recurrence (%)		Total (n)
		no	yes
Caecal location?		94.9	5.1	117
		72.2	27.8	18
Total		91.9%	8.1%	135

Conclusion: Caecal location was associated with over a 5-fold increase (28.7% vs 5.1%) in the incidence of 12 month recurrence. The results from this series confirm the increased technical demands associated with the endoscopic resection of caecal LNPCPs, and are especially noteworthy considering that our study involved experienced BCSP endoscopists only. In view of the increased risk of endoscopic treatment failure, in addition to the established increased risk of adverse endoscopic events, caecal LNPCPs may benefit from multidisciplinary discussion and managed by a select group of advanced endoscopists.

Disclosure of Interest: None declared

P0157 THE DEVELOPMENT OF A MINIMUM DATASET PROFORMA FOR THE MULTIDISCIPLINARY ASSESSMENT AND MANAGEMENT OF LARGE NONPEDUNCULATED COLORECTAL POLYPS

A. Chattree¹², J. A. Barbour³, S. Dolwani⁴, M. D. Rutter¹², on behalf of British Society of Gastroenterology Large Polyp Working Group

¹Gastroenterology, North Tees and Hartlepool NHS Foundation Trust, Stockton on Tees, ²School of Health Sciences, University of Durham, Durham, ³Gastroenterology, Queen Elizabeth II Hospital, Gateshead, ⁴Gastroenterology, University Hospital of Wales, Cardiff, United Kingdom

Contact E-mail Address: amitchattree@nhs.net

Introduction: The lack of any structured framework internationally for the assessment and management of large non-pedunculated colorectal polyps (LNPCPs) appears to have resulted in a wide variation in decision making with regards to endoscopic and surgical management and suboptimal outcomes.¹ Multidisciplinary team discussion has been advocated to better coordinate management. The development of an evidence based and expert approved minimum dataset proforma may complement this process and encourage optimal management resulting in improved outcomes.

Aims & Methods: Following an extensive literature review, various patient and polyp parameters relevant to LNPCP assessment and management were selected. A 14 person British Society of Gastroenterology (BSG) approved multidisciplinary panel participated in Delphi consensus methodology to vote anonymously on the proposed parameters with ≥80% agreement required for consensus to be achieved. The draft proforma was then assessed on a sample of 20 LNPCP cases, resulting in modification after a further voting round.

Results: The final proforma comprised of 17 parameters encompassing all patient and lesion factors considered essential to the decision making process in LNPCP management. Patient parameters included patient symptoms, treatment preferences and comorbidity. Lesion parameters included morphology and surface characteristics (e.g. Paris classifications and Pit pattern) and the specification of any lesion features associated with increased complexity such an increased risk of malignancy, unsuccessful endoscopic resection or adverse endoscopic events². Parameters regarding relevant histology and radiology results and guidance on obtaining adequate lesion imaging were also agreed.

Conclusion: The development and validation of a BSG/ACPGBI minimum dataset proforma allows for structured and comprehensive multidisciplinary discussion in LNPCP management, ensuring that all important factors are discussed and resulting in more coordinated and robust decision-making. This proforma can be used to structure discussions during a multidisciplinary team meeting and all related discussions such as referral to the tertiary setting, in addition to being used as a checklist for comprehensive lesion assessment.

Disclosure of Interest: None declared

P0158 INCREASED PROCEDURE VOLUME LEADS TO IMPROVED ENDOSCOPIC MANAGEMENT OF LARGE NON-PEDUNCULATED COLORECTAL POLYPS

A. Chattree¹², J. Painter³, J. Silcock⁴, D. Nylander⁵, M. D. Rutter¹²

¹Gastroenterology, North Tees and Hartlepool NHS Foundation Trust, Stockton on Tees, ²School of Health Sciences, University of Durham, Durham, ³Gastroenterology, Sunderland Royal Hospital, Sunderland, ⁴Gastroenterology, University Hospital of North Durham, Durham, ⁵Gastroenterology, Royal Victoria Infirmary, Newcastle Upon Tyne, United Kingdom

Contact E-mail Address: amitchattree@nhs.net

Introduction: Confirmation of lesion eradication at least 12 months after endoscopic mucosal resection (EMR) of large non-pedunculated colorectal polyps (LNPCPs) is an internationally recognised marker of therapeutic success¹. Variable outcomes have been reported in international case series, with reported figures of up to 10% recurrent/residual polyp (RRP)². Whilst various technical factors been attributed to the variable outcomes in treatment success, there is a paucity of evidence linking endoscopist advanced endotherapy procedure volume with successful curative resection of LNPCPs.

Aims & Methods: Retrospective analysis was conducted on LNPCPs managed with endoscopic mucosal resection in the North East NHS Bowel Cancer Screening Programme (BCSP) between 2011-14. A comparison of 12 month RRP was made between high volume (≥30 procedures per year) and low volume (<30 procedures per year) endoscopist groups. Statistical analysis was performed using the chi-squared test.

Results: A total of 135 lesions were identified, with 12 month RRP identified in 8.1% of cases. The incidence was higher in the low volume endoscopist group (12.3% (9) vs 3.2% (2),p=0.064).

		12 month recurrence (%)		Total (n)
		no	yes
Endoscopist procedure number	≥30	96.8	3.2	62
	<30	87.7	12.3	73
Total		91.9	8.1	135

Conclusion: A level of 12-month RRP comparable with international series (8.1%), suggests effective LNPCP management within the NHS BCSP. Whilst no statistical association was found between endoscopic volume and curative resection, an almost four-fold increase in failed curative resection was seen in the low volume endoscopist group (12.3% vs 3.2%). It can be argued that our study may be underpowered and that the results indicate clinical relevance. These outcomes also indicate that limiting advanced endotherapy to a select number of experienced therapeutic endoscopists may result in a further improvement in outcomes.

Disclosure of Interest: None declared

P0159 ENDOSCOPIC REMOVAL OF DEFIANT COLORECTAL LESIONS: A RETROSPECTIVE STUDY IN A TERTIARY MEDICAL CENTER

A. Koutsoumourakis¹, G. Lazaraki¹, D. Tzilves¹, I. Pilpilidis¹, K. Soufleris¹, O. Abraam¹, S. Mparmpanis², A. Tarpagkos¹

¹Department of Gastroenterology, ²Department of Histopathology, Theagenio Cancer Hospital, Thessaloniki, Greece

Contact E-mail Address: koutsoumourakis@gmail.com

Introduction: Endoscopic mucosal resection [(EMR) en-block and piecemeal] has been recognized as an effective and less invasive curative endoscopic treatment procedure for large and nonpedunculated colorectal lesions (LNLs) > 20 mm.

Aims & Methods: The aims of the current study were to evaluate EMR complete resection and complication rate for LNLs > 20 mm and to estimate the long-term local recurrence rate afterwards. Data were collected retrospectively by use of the Electronic Endoscopy Report Data Base at our center. A total of 158 patients (84 men, 71.1 ± 7.52 years and 74 women, 70.58 ± 7.49 years) with 158 LNLs > 20 mm were enrolled. All endoscopic resections were performed by experienced endoscopists. All patients underwent standardized follow-up colonoscopy after 3.23 ± 2.43 months and 9.58 ± 6.26 months based on the lesion diameter, location, configuration, histopathology, type of EMR and endoscopic assessment of complete resection, respectively. The resection was regarded as incomplete if histopathologic examination revealed a residual/recurrent adenomatous tissue at the EMR scar site.

Results: En block resection was performed in 43/158 LNLs (27.21%) and piecemeal resection in 115/158 LNLs (72.78%). LNLs mean size was estimated at 34.9 ± 14.5 mm. Histological examination of LNLs showed 30 tubular adenomas (18.98%), 5 villous adenomas (3.26%), 102 tubular-villous adenomas (64.55%), 1 serrated adenoma (0.63%) and 20 adenocarcinomas (12.65%). High-grade dysplasia was detected in 35 LNLs (22.15%) and low-grade dysplasia in 123 LNLs (77.84%). The first follow-up demonstrated 40/102 LNLs (39.21%) with residual/recurrent adenomatous tissue at the EMR scar site while the second revealed 23/87 LNLs (26.43%). The overall post-polypectomy complication rate was 4.43% (major complications 0.63%, one case of bowel perforation, minor complications 3.79% two cases of minor bleeding and three cases of postpolypectomy syndrome). Although, there was no statistically significant correlation between the size of the LNLs and the rate of residual/recurrent neoplasia after the first surveillance colonoscopy (t-test, P= 0.052324, p< 0.05), subsequent statistical analysis showed a strong correlation between the initial size of LNLs and the total rate of late recurrent and residual lesions after the second follow-up examination (t-test, P= 0.0249, p< 0.05). Finally, the use of chi-square test indicated that piecemeal resection is equally effective to en-block resection in LNLs related to recurrent/residual lesions at the previous EMR scar site (χ2 test, P= 0.083, p< 0.05).

Conclusion: EMR is safe and effective for treatment of LNLs > 20 mm. Nonetheless, a substantial portion of residual/recurrent adenomas at the previous EMR scar site can be detected. Therefore, an appropriate very strict follow-up surveillance colonoscopy protocol is necessitated in order to obtain biopsies from previous polypectomy scar sites.

Disclosure of Interest: None declared

P0160 EUROPEAN COLONOSCOPY QUALITY INVESTIGATION GROUP: IMPROVING STANDARDS IN COLONOSCOPY THROUGH A PRACTICE LEVEL AUDIT TOOL

J. F. Riemann¹, I. Demedts², A. Agrawal³, R. Jover⁴, A. Ono⁵, P. Amaro⁶, E. Toth⁷, P. Eisendrath⁸, A. Naidoo⁹

¹Emer. Dir., Klinikum Ludwigshafen, Ludwigshafen, Germany, ²UZ Leuven, Leuven, Belgium, ³Doncaster Royal Infirmary, Doncaster, United Kingdom, ⁴Hospital General Universitario de Alicante, Alicante, ⁵Virgen de la Arrixaca University Hospital, Murcia, Spain, ⁶Coimbra University Hospital, Coimbra, Portugal, ⁷Skåne University Hospital, Malmö, Sweden, ⁸Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium, ⁹Norgine Limited, Uxbridge, United Kingdom

Contact E-mail Address: anaidoo@norgine.com

Introduction: Colorectal cancer is a major cause of morbidity and mortality worldwide. Colonoscopy remains the investigation of choice for both diagnosis and screening, and many countries have implemented screening programmes to allow for early detection. The European Society of Gastrointestinal Endoscopy quality in colonoscopy position statement highlights key quality indicators in colonoscopy and concluded that the success of screening programmes is related to the prompt provision of high quality, patient centred colonoscopy service. The European Colonoscopy Quality Investigation (ECQI) group of leading European clinicians developed a practical tool to enable audit of current clinical practice across Europe to assess whether quality standards are being achieved, and to identify, test, and implement practical ways of improving quality in colonoscopy.

Aims & Methods: The aim was to understand how quality is evaluated in current clinical practice via the development and implementation of an online tool to audit colonoscopy practice. At the inaugural meeting in 2013, the ECQI group recommended a clinical practice level audit tool to be developed to enable colonoscopists to audit their own practice. The audit tool was designed to encourage improvement in overall outcomes (e.g. adenoma detection rate), and to ensure consistency and high standards across clinical practice, within countries and across Europe, and was validated by the group in September 2014. A phase 1 pilot to test this tool was performed in November 2014, with early outputs discussed by the group in December 2014. The audit tool was further revised to improve usability via a collaborative iteration process.

Results: The online audit tool was piloted at centres across 10 European countries with 313 patient visits recorded on the initial questionnaire during a 1-week period. Questions included: patient demographics, the status and experience of the practitioner performing the endoscopy, details of the bowel preparation procedure used and the quality of bowel cleansing achieved, colonoscopic findings, and follow up arrangements. Following the review of the phase 1 pilot, consensus from the ECQI group resulted in the refinement of the tool to create an updated version which included three separate sections: Practitioner, Centre and Patient level questionnaires to improve efficiency of use. This will form part of a second phase pilot planned for 2015.

Conclusion: The creation of the ECQI Group enabled the development of a validated, practice level audit tool to enable clinicians to audit their own practice. This tool will be tested in a second pilot phase, and its value will be further evaluated by the Group in order to make recommendations for its use across Europe. The range of experience and geographical spread of the participants allows for quality evaluation to be compared across practices and countries. The longer term aim of this project is to enhance the quality of colonoscopy at a practice level by enabling clinicians to be involved in improving their own practice.

Disclosure of Interest: J. Riemann Consultancy: Advisory board participant for Norgine, I. Demedts Consultancy: Advisory board participant for Norgine, A. Agrawal Consultancy: Advisory board participant for Norgine, R. Jover Consultancy: Advisory board participant for Norgine, A. Ono Consultancy: Advisory board participant for Norgine, P. Amaro Consultancy: Advisory board participant for Norgine, E. Toth Consultancy: Advisory board participant for Norgine, P. Eisendrath Consultancy: Advisory board participant for Norgine, A. Naidoo Conflict with: Employee of Norgine

P0161 UNDERWATER ENDOSCOPIC MUCOSAL RESECTION: THE THIRD WAY FOR EN BLOC RESECTION OF COLONIC LESIONS? A CASE SERIES

A. Amato¹, F. Radaelli¹, S. Paggi¹, E. Rondonotti¹, G. Spinzi¹

¹Gastroenterology, Valduce Hospital, Como, Italy

Contact E-mail Address: arnamato@gmail.com

Introduction: Underwater endoscopic mucosal resection (UEMR) has been described since 2012 for removing large colorectal non polypoid lesions^1,2,3,4; it is based on filling the colonic lumen with water and it differs from traditional endoscopic mucosal resection since it does not require sub-mucosal injection.

Aims & Methods: To evaluate the reproducibility of this new endoscopic technique in terms of ease of implementation, safety and efficacy. UEMR prospectively performed in a community hospital were gathered.

Results: From September 2014 to February 2015 20 colorectal non polypoid lesions (median size 24.7 mm, range 10-50mm) have been removed in 20 patients (12 women; median age 62.2 years). Two of the lesions were adenomatous recurrences on scar of previous resection and one was a recurrence located on a surgical anastomosis. Five lesions were located in the cecum, seven in the ascending colon, two in the transverse colon, one in the descending colon, one in the sigmoid colon and three in the rectum.

In 16 lesions (80%) the resection was performed en bloc, whereas 4 (20%) were removed by piece-meal resection. At the pathological examination six lesions had non advanced histology, 10 lesions had advanced histology and 4 were SSA, one of which with high grade dysplasia.

Complete resection was observed in all the sixteen lesions removed en bloc.

A complication (intra-procedural bleeding, endoscopically managed with no consequences) was observed in the first two UEMR.

Conclusion: UEMR appears an easy, safe and effective technique also in community setting. Further studies comparing UEMR and conventional EMR in terms of complete resections and evaluating the early and late recurrence are needed.

Disclosure of Interest: None declared

P0162 IS WATER-ASSISTED COLONOSCOPY SUPERIOR TO CARBON DIOXIDE ASSISTED STANDARD COLONOSCOPY: RESULTS OF AN OBSERVATIONAL STUDY

A. K. Kurup¹, S. Shetty¹, S. Ishaq¹

¹Gastroenterology, Russells Hall Hospital, Dudley, United Kingdom

Contact E-mail Address: drarunkumar_uk@hotmail.com

Introduction: Water-assisted colonoscopy [WAC] is known to reduce patient discomfort and improve the adenoma detection rate [ADR] [1]. In this retrospective observational study, we compared water assisted colonoscopy against standard colonoscopy [SC] using CO2 in a bowel cancer screening positive population.

Aims & Methods: This was a retrospective review of prospectively collected data. The population studied was undergoing colonoscopies following a positive faecal occult blood test as part of the bowel cancer screening programme [BCSP]. Endoscopist A preferred to intubate the caecum using the water exchange method and endoscopist B would insufflate the bowel using carbon dioxide. Sedation and analgesic use was at the discretion of the endoscopist. The primary outcome was the adenoma detection rate and the comfort scores in the two groups. Secondary outcomes included caecal intubation rate, mean withdrawal time, sedation use and polyp retrieval rate.

Results: Data from two hundred and seven colonoscopies performed from April 2014 to December 2014 [9 months] were analyzed. 102 colonoscopies were performed using the water exchange method [group A] and 105 colonoscopies were performed using CO2 [group B].

Primary outcomes:

Adenoma detection rate [ADR] in group A was 53% compared to of 36% in group B.This was statistically significant [difference in rate =-0.1868 [95% CI 0.0052- 0.3685 p=0.0438].

The proportion of patients experiencing none [score 1] or minimal [score2] discomfort [based on modified Gloucester comfort score] were more in group A [n=74] compared to group B [n=62]. This was found to be statistically significant [Z= 2.046, p=0.0408].

Secondary outcomes:

Indicator	Group A	Group B
Caecal intubation rate	95%	97%
Mean withdrawal time	8.4 minutes	7 minutes
Polyp retrieval rate	93%	95%
Intravenous sedation	68	87
Entonox only	30	13

Conclusion: Our finding of a significant improvement in ADR and better tolerability in the WAC group supports similar conclusions by Hsieh et al. This may have potential implications for the bowel cancer screening programme since the perception of colonoscopy can influence public participation and improve uptake in the BCSP. Improved ADR may be due to combination of factors like improved bowel preparation, flattening of mucosal folds and floating effect of polyps with water irrigation.

Disclosure of Interest: None declared

P0163 EFFECT OF HIGH BMI ON ADEQUACY OF BOWEL PREPARATION & COLONOSCOPY PERFORMANCE

A. Hussain¹, M. Al-Ansari¹, N. Smith¹, A. Zad¹, A. Tung¹

¹Gastroenterology, Ballarat Hospital, Ballarat, Australia

Contact E-mail Address: drasifhussain@hotmail.com

Introduction: There is limited evidence regarding the effect of high body mass index (BMI) on colonoscopy performance. Given the prevalence of high BMI in regional communities, this association may impact on the already limited resources within regional hospitals [1,2].

Aims & Methods

Objective: To determine if there is an effect of high BMI on bowel preparation and colonoscopy performance.

Design: A single centre prospective study at a teaching hospital in Ballarat, Victoria, Australia between May 2012 and November 2014. Patients undergoing colonoscopy for any indication were included.

Method: Patients were divided into two groups, BMI ≥25 or BMI <25. Colonoscopies were performed by 17 experienced endoscopists and the data collected by trained endoscopy nurses. Bowel preparation was assessed using the Ottawa Bowel Preparation Scale. Colonoscopy performance was assessed using caecal intubation times (short up to 6 minutes, intermediate = 7-9 minutes and long ≥ 10 minutes). Chi-square statistical analysis was used to determine significance (p = <0.05).

Main outcome measurements: Adequacy of bowel preparation and caecal intubation time.

Results: A total of 2026 colonoscopies were performed during the study period. 74% of participants had a BMI ≥25. Both the low BMI and the high BMI groups has similar adequacy of bowel preparation (93%, p = 0.16). Short caecal intubation time (up to 6 minutes) was 29% for patients with normal BMI, and 35% for patients with high BMI. 28% of patients with a normal BMI had an intermediate caecal intubation versus 23% for patients with high BMI. For patients with a long caecal intubation time, 41% had a normal BMI, compared to 42% of patients with a high BMI, which was not statistically significant (p= 0.37).

Discussion: In this study we found that high BMI is extremely prevalent in the Ballarat population. However, high BMI did not contribute to a statistically significant difference in the quality of bowel preparation or colonoscopy performance. This prospective study, showing important negative results, has a good sample size and was conducted by 17 experienced colonoscopists. However being a single-centre study, the generalizability of the results is limited.

Conclusion: The study has shown that there is no correlation between high BMI and colonoscopy performance. A multicentre study may be helpful in further establishing significance of high BMI and colonoscopy performance.

Disclosure of Interest: None declared

P0164 PROSPECTIVE RANDOMIZED COMPARISON OF THE SAFETY AND EFFECTIVENESS OF ANESTHESIOLOGIST-ADMINISTERED PROPOFOL ALONE VERSUS PROPOFOL AND NALBUPHINE DEEP SEDATION FOR OUTPATIENT COLONOSCOPY

B. Gellert¹, L. Madacsy², M. Murányi², I. Hritz²

¹Department of Gastroenterology, Semmelweis University, Budapest, ²Department of Gastroenterology, Endo-Kapszula Endoscopy Unit, Székesfehérvár, Hungary

Contact E-mail Address: endomabt1@gmail.com

Introduction: Colonoscopy is nowadays routinely carried out under propofol deep sedation. Nalbuphine is a widely used major analgetics and is an ideal drug to reduce the given propofol dose during outpatient colonoscopy. The aim of our present prospective, randomized study was to evaluate the safety and effectiveness of 397 ambulatory colonoscopies carried out under propofol versus propofol and nalbuphine deep sedation with respect to endoscopic success rate, complications and patient satisfaction.

Aims & Methods: 190 patients received nalbuphine and propofol and another 207 patients received propofol alone in a randomized manner. The cecal intubation rate, the incidence of major and minor cardiovascular and respiratory complications during deep sedation in terms of the mean of the highest and lowest blood pressure and heart rate values were prospectively measured (BPmax and BPmin mean, Pmax and Pmin mean) as well as changes in oxygen saturation (SpO2) were calculated. The propofol induction and total dose, the time from induction to spontaneous awakening, the recovery time and Post Anesthetic Discharge Scoring System (PADSS) were also compared.

Results: No significant differences in the cecal intubation rate was demonstrated in the nalbuphine and propofol vs. propofol groups: 98.4% vs. 96.8% (p=0.4). No major cardio-respiratory complications lasting more than 2 minutes occurred. The induction propofol dose was 40 ± 13 mg vs. 74 ± 45 mg, and the corresponding mean total doses of propofol was 80.5 ± 32.7 mg and 142.9 ± 88.1 mg in the two groups, respectively (p < 0.05). Comparison of patients groups with nalbuphine and propofol versus propofol administration alone depicted no significant differences regarding to the mean awakening time 30.4 min ± 10.7 vs. 29.3 min ± 9.4, (p=0.3), and the mean recovery time 51.7 min ± 23.3 vs. 68.1 min ± 29.5 (p=0.4). However, and the results of PADSS was significantly different, and demonstrated more gastrointestinal symptoms to prevent timely patient discharge in some of patients in the nalbuphine group (p < 0.05).

Conclusion: Colonoscopy procedures implemented in propofol deep sedation administered by an anesthesiologist turned out to be completely safe procedure, with excellent coecum intubation rate and optimal patient satisfaction. Low-dose nalbuphine combined with propofol is an effective and economic alternative in the reduction of propofol needs, but gastrointestinal side effects of morphine agonists significantly reduce the PADSS and may prevent timely patient discharge.

Disclosure of Interest: None declared

P0165 RELATIONSHIP BETWEEN THE POSITION OF THE ILEOCAECAL VALVE IN THE COLONIC CIRCUMFERENCE AND THE FEASIBILITY OF ITS INTUBATION

B. Velayos¹, L. Del Olmo¹, N. Alcaide¹, M. F. Muñoz², J. M. González¹

¹Department of Gastroenterology, ²Investigación Unit, Hospital Clínico de Valladolid, Valladolid, Spain

Contact E-mail Address: benitovelayos@hotmail.com

Introduction: Ileal intubation is an important goal in colonoscopy practice.

We have studied if the position of the ileocaecal valve in the colonic circumference can determine a feasible and prompt ileal intubation.

Aims & Methods: We randomized 177 consecutive patients (mean age: 56 yrs; range: 13-87 yrs; 52% males) in which we reached a clean caecum to supine (62.7%) and right-lateral decubitus posture (37.3%).

This two postures resulted in different positions of the ileocaecal valve: 5.7% in the quadrant I (2 o'clock: 2.3%, 3 o'clock: 1.1% and 4 o'clock: 2.3%); 20.3% in the quadrant II (5 o'clock: 3.4%, 6 o'clock: 5.6% and 7 o'clock: 11.3%); 43.5% in the quadrant III (8 o'clock: 7.9%, 9 o'clock: 15.3% and 10 o'clock: 20.3%) and 30.5% in the quadrant IV (11 o'clock: 20.9%, 12 o'clock: 7.3% and 1 o'clock: 2.3%).

With the scope shortened and de-looped we moved it back to the ileocaecal valve, trying to get into the ileum (at least 3 cm) with the tip.

Results: Successful ileal intubation was achieved in the first attempt (16.9%), in the first three attempts (71.7%), or in the first five attempts (89.2%).

We did not find statistically significant difference in accomplishment ileoscopy in the first attempt depending on quadrant (p=0.158) nor o`clock position (p=0.189), because of the low percentage of success in this case, but we did for the first three attemps (p=0 for quadrant; p=0 for o´clock position) and for the first five attemps (p=0.005 for quadrant; p=0 for o`clock position).

Quadrant III and 10 o`clock position were the best locations for a quick ileoscopy.

Conclusion: The exact position of the ileocaecal valve in the colonic circumference, a modifiable condition by changing the patient's posture, can determine success in its intubation and promptness to get it.

This is a scarcely analyzed point that could improve safety and comfort for patients undergoing in colonoscopy.

Disclosure of Interest: None declared

P0166 PREDICTORS OF INADEQUATE BOWEL PREPARATION FOR COLONOSCOPY: A PROSPECTIVE STUDY

C. Leitão¹, H. Ribeiro¹, J. Pinto¹, A. Caldeira¹, R. Sousa¹, J. Tristan¹, A. Banhudo¹

¹Serviço de Gastrenterologia, Hospital Amato Lusitano - Unidade Local de Saúde de Castelo Branco, Castelo Branco, Portugal

Contact E-mail Address: catia.f.leitao@gmail.com

Introduction: Inadequate bowel preparation remains a common problem on our daily clinical practice and is associated with canceled procedures, prolonged procedure time, incomplete examination, but most importantly, with missed pathology.

Aims & Methods: This prospective study was designed to assessment the quality of intestinal preparation and evaluate potencial factors associated with an inadequate level of bowel preparation.

Methods: We prospectively studied consecutive outpatients who had colonoscopies performed at our hospital between March and December 2013. Patients’ data were analyzed and a questionnaire was applied to the gastrenterologist after the examination. The grade of intestinal preparation was evaluated using the Aronchick preparation assessment scale.

Results: A total of 196 patients were enrolled into the study (51.2% male; with a mean age of 64 ± 13 years). Only 10.6% of patients were not able to follow the bowel preparation instructions and 34.0% described a poor tolerability to the bowel preparation. An excellent or good bowel preparation was achieved in 61.7% and a fair, poor or inadequate intestinal preparation was reported in 38.3% of observed colonoscopies. An earlier colonoscopy start time (p < 0.034), age greater than 65 years (p < 0.014), male gender (p < 0.001) and higher weight (p < 0.034) were independent predictors of an inadequate intestinal preparation. There was no significant difference in the quality of bowel preparations among the types of bowel preparations administered to the patient, the tolerability of bowel preparation and the quality of preparation instructions (p > 0.05).

Conclusion: This prospective study identified several factors that may predict inadequate bowel preparation irrespective of bowel preparation type, compliance with preparation instructions and tolerability. This information may help to identify patients at an increased risk for inadequate colonic preparation for whom the personal education would be appropriate.

Disclosure of Interest: None declared

P0167 COLORECTAL ENDOSCOPIC SUBMUCOSAL DISSECTION IN A WESTERN TERTIARY REFERRAL CENTRE. ANALYSIS OF 173 CASES: LONG-TERM RESULTS AND IDENTIFICATION OF POSSIBLE RISK FACTORS FOR TECHNICAL DIFFICULTY

C. Snauwaert¹, H. Piessevaux¹

¹Gastroenterology and Hepatology, Cliniques Universitaires Saint-Luc, Brussels, Belgium

Contact E-mail Address: christophe.snauwaert@hotmail.com

Introduction: Colorectal endoscopic submucosal dissection (CR-ESD) enables en-bloc resection of lesions > 2 cm which would otherwise require piecemeal removal. However, CR-ESD is still considered as a technically challenging procedure and is not widespread outside Asian expert centres.

Aims & Methods: Our aim was to assess efficacy, safety and long-term results for CR-ESD and identify possible risk factors for technical difficulty. We analysed charts from 173 consecutive patients who underwent CR-ESD between May 2006 and July 2013. Efficacy and safety endpoints were complete en-bloc resection rates, endoscopic and histological remission and post-procedural complications.

Results: Median age of patients was 67 years (IQR 58-76). Lesions were located throughout the colon with predominance for the caecum and rectum: ileo-anal pouch (1.2%), ileo-caecal valve (4.6%), caecum (21.4%), ascending colon (11.6%), hepatic flexure (6.9%), transverse colon (4%), splenic flexure (2.3%), descending colon (1.7%), sigmoid colon (6.4%) and rectum (39.9%). Median longest and perpendicular diameter of lesions was 35mm (range 10-150mm) and 30mm (range 8-130mm) respectively. Most lesions were classified as Paris 0-IIa (45.1%), 0-Is (29.5%) and 0-IIb (17.3%). Forty-eight percent of lesions were classified as LST-NG according to the Japanese classification. In 15.6% of cases a previous resection had been attempted elsewhere. Full ESD was performed in 117 (68%) patients; the remainder was treated using a hybrid technique of circumferential submucosal incision, dissection and finally followed by en-bloc snare resection. Median procedure duration was 109 minutes (IQR 70-157). The en-bloc resection rate was 74.6% (129/173). Previous attempt at resection was a significant risk factor for en-bloc resection failure (40.8% vs. 22.7%; p < 0.05). Twenty-one (12.1%) perforations occurred during ESD, which were all successfully managed by endoscopic clip closure. One or more post-procedure complications occurred in 46 patients (26.9%) of which 15 delayed perforations (8.6%). The complication rate decreased significantly with growing experience (e.g. 14 delayed perforations for the first 87 cases vs. 1 for the last 86 cases; 16% vs. 1%; p < 0.05). Two patients required surgery for post-procedural perforation salvage. Median hospital stay was 2 days (IQR 2-2). The majority of lesions (114/173; 65%) contained high-grade dysplasia or more advanced histopathology (Table 2). Free vertical margins were achieved in 92% (160/173) of patients. Fourteen patients underwent additional surgical resection because of incomplete resection or unfavourable histology. Endoscopic follow-up was available in 154 patients. During the median follow-up period of 13 months (IQR 3-24), 2 small mucosal recurrences occurred which were resected endoscopically.

Conclusion: CR-ESD is effective with very low local recurrence rates. Previous attempts at snare resection are predictive for en-bloc resection failure. In general, post-procedural course is favourable with short hospitalisation stays. Complications (especially delayed perforation) have to be considered, but usually can be managed conservatively. A growing level of experience significantly reduces the post-procedural complication rate.

Disclosure of Interest: None declared

P0168 THE USEFULNESS OF BALLOON OVERTUBE-ASSISTED COLORECTAL ENDOSCOPIC SUBMUCOSAL DISSECTION WITH A RUBBER BAND TISSUE TRACTION DEVICE

D. Ide¹, S. Saito¹, S. Kamba¹, H. Inomata¹, N. Tamai¹, K. Sumiyama¹

¹The Jikei University Hospital, Tokyo, Japan

Contact E-mail Address: dei0405@jikei.ac.jp

Introduction: The gastroscope is often used even for colorectal ESD on a priority basis because operational performance is suitable to procedure in our facility. However, anatomic variability in the colon may hinder any endoscopic intervention. In cases which access to the lesion with a gastroscope was difficult, we used a balloon overtube as an endoscopic channel for colorectal ESD. In addition, to enable a more safe and efficient procedure, we combined balloon overtube- assisted ESD with a rubber band tissue traction device (RTD), designed to be fixed on freed edges of a mucosal overlay with clips to deflect the diseased mucosa away from the dissection plane.

Aims & Methods: We aimed to evaluate the utility of balloon overtube- assisted colorectal ESD with a RTD as needed. At The Jikei University Hospital from April 2012 to December 2014, we performed ESD in colorectal lesion for 311 patients. In the preoperative evaluation of accessibility with a gastroscope, thirty one patients were identified as difficult, and were enrolled in the balloon overtube- assisted ESD and retrospectively examined.

Abstract number: P0168

	Ratio of the use of RTD	M or SM slightly cancer/SM deeply cancer	Protoruded/ Flat elevated/ Others	Cecum/Right colon/Left colon/Rectum	Mean size of specimen	Mean time of procedure	Ratio of curative resection	Ratio of complication Perforation/Bleeding
Standard (n: 280)	33.2%	261/19	114/158/8	27/115/64/74	39.9mm (18-150)	62.8min (5-560)	91.1%	1.4%/2.9%
Overtube (n: 31)	29.0%	30/1	12/18/1	10/21/0/0	40.1mm (25-71)	63.7min. (20-212)	83.8%	0%/0%

Conclusion: There were little practical differences between the standard ESD method using a gastroscope without the overtube and the balloon-assisted ESD method in term of outcome for therapy. This result suggested that use of the balloon overtube is an effective for colorectal ESD, when lesions are located at difficult positions in the right side colon. Furthermore, as the situation demands, using the RTD for colorectal ESD was also suggested to effective procedure.

Disclosure of Interest: None declared

P0169 CECAL INTUBATION RATE (CIR) CORRELATES WITH ADENOMA DETECTION RATE (ADR) BUT HAS NO IMPACT ON ADVANCED ADENOMA DETECTION RATE (AADR)

D. Sallinger¹², E. Waldmann¹², P. Jeschek¹², I. Gessl¹², M. Britto-Arias¹², B. Majcher¹², A. Dokladanska¹², M. Gschwantler², M. Trauner¹², M. Ferlitsch¹²

¹Div. of Gastroenterology and Hepatology, Dept. of Internal Medicine III, Medical University of Vienna, ²Quality Assurance Working Group, Austrian Society of Gastroenterology and Hepatology (OEGGH), Vienna, Austria

Contact E-mail Address: daniela.sallinger@meduniwien.ac.at

Introduction: Incomplete screening colonoscopy can result in missing precancerous lesions, such as adenomas. By a study of Kaminski et al., cecal intubation rate (CIR) as a major quality indicator, showed to be not associated with higher risk of interval cancer.

Adenoma detection rate (ADR) is considered a main quality measure in screening colonoscopy and should be at least 20%. Advanced adenomas (AA) carry greater risk for progression to cancer than non-advanced adenomas and should be detected early.

Because of lack association between CIR and the risk of interval cancer, our primary aim was to investigate whether there is a correlation between CIR and ADR. Further we wanted to assess if CIR correlates with AADR and if findings differ between high (≥95%) and low CIR-group (<95%).

Aims & Methods: Within the Austrian quality assurance program, 148.284 colonoscopies performed by 197 endoscopists were analyzed. Spearman rank-order was used to assess correlation between CIR and ADR, as well as AADR.

Results: Median CIR was 97.38% [Interquartile range (IQR)=94.24%>98.65%] and ranges from 72.95%>100%. Median ADR was 21.37% (IQR=16.25%>27.78%) with a minimum of 4.45% and a maximum of 43.06%. Median AADR was 5.43% (IQR= 3.71%>8.40%) with a range from 0.00% to 20.93%.

Spearman rank order coefficient (r_s) of 0.222 showed a significant correlation between CIR and ADR (p < 0.001). AADR was independent of CIR (R_s=-0.024; p=0.735) within both groups of endoscopists, those with CIR <95% (r_s=0.152; p=0.251; n=59) as well as within high (≥95%) CIR-group (r_s=-0.036; p=0.679; n=138).

Conclusion: CIR correlates with ADR but has no impact on participants’ detection of advanced adenomas, which could explain the lack of impact of CIR and the risk of interval cancer in the study of Kaminski et al.

Disclosure of Interest: None declared

P0170 IDENTIFICATION OF COLONOSCOPY COMPLICATIONS RATE IN 6 SPANISH COLORECTAL CANCER SCREENING PROGRAMMES

D. Salas¹, I. Portillo², M. E. Oceja³, M. De la Vega⁴, F. Pérez-Riquelme⁵, J. A. Espinàs⁶, E. Pérez-Sanz¹, M. Vanaclocha¹, J. Ibañez¹, A. Molina-Barceló¹, on behalf of CRIBEA group

¹Department of Public Health and Foundation for the Promotion of Health and Biomedical Research in the Valencian Region, FISABIO – Public Health, Valencia, Spain, Ministry of Health of Valencian Region, Valencia, ²O Central Osakidetza., P.Vasco, ³DG.Salud Pública, Cantabria, ⁴DG.Progr. Asistenciales, Canarias, ⁵DG. Salud Pública, Murcia, ⁶P.Director Oncología, Cataluña, Spain

Contact E-mail Address: salas_dol@gva.es

Introduction: In Spain, colorectal cancer screening programmes (CRCSP) are being progressively implemented, with 28% coverage (for all Spanish population) in 2014. The regions of Canarias, Cantabria, Cataluña, Murcia, País Vasco and Valencia participate in the CRIBEA Project with the aim to identify CRC screening benefits and warms (FIS PI12/00944, financed by FEDER funds). The programmes are directed at men and women between 50 and 69 years of age with the aim to reduce CRC incidence and mortality. The screening test is a biennial faecal occult blood test (FOBT), and the confirmation test is a colonoscopy. Colonoscopy complications are one of the adverse effects of screening, and could be immediate (during the exploration) or deferred (post-exploration). Immediate complications are easy to identify and register but deferred ones not, because of ignorance of the time that occurs.

Aims & Methods

Aim: To estimate the severe complications rate (immediate and deferred at 30 days) in the context of further investigation colonoscopies (after positive FOBT) in the context of 6 Spanish CRCSP according to the European definition of severe complication (severe bleeding that requires transfusion, intestinal perforation, severe vagal syndrome, similar to peritonitis syndrome).

Method: Retrospective population-based cohort study, defined by the population with colonoscopy performed in 6 regions of Spain with CRCSP from 2000 to 2012. Information sources: the screening information system and the Minimum Set Basic Data (MDS) information system (mandatory in all hospitals). The identification process of complications is managed by crossing the personal identifiers of people with screening colonoscopy and the hospital admissions 30 days after the colonoscopy performance. Matched people are identified using CIE-9 codes.

Results: A total of 2.15413 million invitations and 959 249 people participated in these regions. People with positive FOBT were 52.913, and 47.008 colonoscopies were performed. The complication rate for both sexes was 5.02 per thousand colonoscopies (236/47008), men being 5.51% (151/27402) and women 4.34% (85/19606). Complication rate for the age group 50-59 was 3.76%, and for 60-69 was 4.57%.

Conclusion: A significant number of deferred screening colonoscopy complications need to be identified in hospital registries. The severe complications rate is 5.02 per 1000 colonoscopies. The complication rate was higher in men versus women and in the age group of 60-69 years versus 50-59.

Disclosure of Interest: None declared

P0171 THE IMPACT OF “BEHIND FOLDS VISUALIZING” COLONOSCOPY – A POOLED ANALYSIS OF RANDOMIZED BACK-TO-BACK TANDEM COLONOSCOPY STUDIES

E. C. Brand¹, V. K. Dik¹, M. G. van Oijen¹², P. D. Siersema¹

¹Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, ²Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands

Contact E-mail Address: P.D.Siersema@umcutrecht.nl

Introduction: The Third Eye Retroscope, Full Spectrum Endoscope (FUSE) and EndoRings have been developed to improve visualization behind colonic folds and have individually been shown to reduce overall adenoma miss rates. Using a pooled analysis, we evaluated for which adenoma characteristics and in which patient subgroups “behind folds visualizing” techniques are most optimal to reduce miss rates.

Aims & Methods: Data of three independent multicentre randomized trials (NCT01044732; NCT01549535; NCT01955122) were combined. Patients underwent same-day, back-to-back tandem examinations with both standard colonoscopy and Third Eye Retroscope, FUSE or EndoRings colonoscopy, respectively. In a pooled analysis we determined adenoma miss rates stratified by adenoma characteristics and patient subgroups.

Results: A total of 650 patients (60% male, mean age 57.5 ± 9.7 years) were randomized, of which 320 patients underwent standard colonoscopy first and 330 patients underwent “behind folds visualizing” colonoscopy first. Adenoma miss rates with “behind folds visualizing” colonoscopy were significantly lower compared to standard colonoscopy for proximally and distally located adenomas, for ≤5mm and 6-9mm adenomas, for sessile, flat and tubular adenomas, and for serrated lesions (Table). The miss rates were not statistically significantly different for ≥10mm, pedunculated, (tubulo)villous and advanced adenomas. Adenoma miss rates were significantly lower with “behind folds visualizing” colonoscopy independent of gender and indication, and in all persons ≥50 years.

Abstract number: P0171 Table. Ade.

noma miss rate per adenoma characteristic and patient subgroup.

Adenoma characteristics		Standard colonoscopy	“Behind folds visualizing” technique
		Missed/total (%)	Missed/total (%)	P-valuea
All adenomasb		93/255 (36)	37/264 (14)	<0.001
Localization	Proximal colon Distal colon	51/135 (38) 42/119 (35)	21/156 (13) 16/108 (15)	<0.001  < 0.001
Adenoma size	≤5mm 6-9mm  ≥ 10mm	71/189 (38) 19/43 (44) 3/23 (13)	34/203 (17) 3/38 (8) 0/23 (0)	<0.001  < 0.001 0.233
Morphology	Pedunculated Sessile Flat	3/24 (13) 73/195 (37) 14/27 (52)	1/39 (3) 34/209 (16) 1/11 (9)	0.150 < 0.001 0.014
Histology	Tubular(Tubulo)villous	84/223 (38) 4/19 (21)	35/238 (15) 0/16 (0)	<0.001 0.109
Advanced adenomasc		6/35 (17)	1/32 (3)	0.108
Serrated lesionsd		4/8 (50)	1/14 (7)	0.039
Patient subgroups
Gender	Female Male	27/61 (44) 66/194 (34)	11/61 (18) 26/203 (13)	0.002  < 0.001
Age	<50 years 50-60 years  > 60 years	4/11 (36) 40/103 (39) 49/141 (35)	3/18 (17) 14/102 (14) 20/144 (14)	0.375  < 0.001  < 0.001
Indication	Screening Surveillance Diagnostic workup	30/103 (29) 43/98 (44) 20/54 (37)	18/113 (16) 15/111 (14) 4/40 (10)	0.020  < 0.001 0.003

^aCalculated using chi-square or Fisher’s exact test where appropriate. ^bIncluding 2 adenocarcinomas. ^cAny adenoma with villous features, high-grade dysplasia or ≥10mm. ^dSerrated lesions are counted separately from adenomas.

Conclusion: “Behind folds visualizing” colonoscopy reduces miss rates in all segments of the colon for 1-9mm adenomas; no significant differences were found for larger (≥10 mm) and advanced adenomas. Whether the detection of more small (<10mm) adenomas indeed reduces CRC incidence and mortality remains to be determined.

Disclosure of Interest: E. Brand: None declared, V. Dik: None declared, M. van Oijen: None declared, P. Siersema Conflict with: is in the advisory board of EndoAid Ltd.

P0172 ENDOSCOPIC SUBMUCOSAL DISSECTION LEARNING CURVE: EXPERIENCE OF A LARGE VOLUME COLONOSCOPY CRC ITALIAN SCREENING CENTER

E. Rosa-Rizzotto¹, E. Guido¹, D. Caroli¹, A. Dupuis¹, M. Lo Mele², M. Rugge², P. Pilati³, F. De Lazzari¹

¹Gastroenterology Unit, ²Surgical Pathology and Cytopathology Unit, ³Surgery Unit, Padova, Italy

Introduction: endoscopic submucosal dissection (ESD) is an advanced endoscopic technique that allows for curative resection of superficial neoplasms in GI tract. The vast majority of experience and guidelines for ESD resection comes from Japan, wehere this technique was developed more than 10 years ago. In East countries the training curve is done on gastric GI lesions with expert supervision before starting on esophageal and colon lesions. In West countries EGC is a rare desease and expert guidance is not commonly available, so the learning courve of this tecnhique has to be developed in a different way.

Aims & Methods: To demonstrate that the ESD learnig curve performed on rectal lesions is a good way to practice on these difficult procedure in European countries. We retrospectovely included in the study all the ESD performed in our Endoscopy Unit in Padua from february 2012 to april 2015. None neplastic lesions come frome other endoscopy units. We considered the learning curve of a single dedicated endoscopist that before starting on humans performed 10 ESD on in vivo animal models under expert guidance. All the dissections were performed using Hybridknife needle and ERBEJET2 (ERBE^®). Complications after procedure like bleeding and perforation were managed with hemoclips, Over the scope clips and hemostatic forceps. ESD was performed if the neoplastic lesion was considered susceptible to ESD regardless to the size. T test for unpaired data and Pearson chi-test were used for ststistical analysis.

Results: 40 ESD were performed, 22M(55%) and 18F(45%), mean age 63yr. 27 rectum (68%), 9 sigmoid tract (23%), 1 trasverse colon (2%), 3 ascending colon (7%). The neoplastic lesions were: 31 laterally spreading tumors (77%), 2 polipoid lesions 0-Is (5%), 3 recurrent tumor on scar (8%), 4 polipoid lesion 0-Isp(10%). Mean polyp area was 17.5 cm². Mean intervention time 107 min. En-bloc dissection was successful in 25/40 (63%) and R0 was reached in 18/24 (75%). Polyps hystological features were: 10 LGD (25%), 21 HGD (53%), 6 pT1 (15%), 3 pT2 (7%). Procedural complications accurred in 12/40 (30%): perforation in 8/40(20%), delayed bleeding 2/40(5%), rectal stenosis 2/40(5%). No deaths or surgical interventions followed the procedural complications. From the 12^th procedure onwards the en-bloc performance became acceptable 22/27(81%) vs 3/12(25%) (p < 0.001). From the 30^th procedure onwards the en-bloc performance became good 9/10 (90%, p < 0.05) and the mean execution time was significantly lower 55 vs 122 min (p < 0.0001) with no significant difference in the mean area of the lesions 15.6 vs 18.2 cm² (p=ns). Only 1 complication occurred after the 30^th procedure (p=ns).

Conclusion: In our experience to reach an acceptable confidence with ESD procedure starting the training from in vivo animal model (at least 10 procedures) and then to colo-rectal neoplasms no less than 12 procedures had to be performed, but we still probably havent yet reached the learning curve plateau also after 40 procedures.

Disclosure of Interest: None declared

P0173 A NEW TECHNIQUE IN TREATMENT OF GIANT LATERAL SPREADING TUMORS WITH ENDOSOCPIC SUBMUCOSAL DISSECTION; POCKET CREATION TUNNELING METHOD

F. Aslan¹, Z. Akpınar¹, E. Alper¹, B. Ünsal¹

¹Gastroenterology, Katip Celebi University Ataturk Training and Research Hospital, Izmir, Turkey

Contact E-mail Address: drfatihaslan@hotmail.com

Introduction: Endoscopic submucosal dissection (ESD) has been widely accepted as an effective and minimally invasive treatment for patients with premalignant lesions. ESD allows en-bloc resection of a lesion, irrespective of the size lesion. However, en-bloc resection of large laterally spreading tumors (LST) with ESD is difficult technically because of anatomical features of the colon including its longer length, narrower lumen, and thinner walls and needs longer procedure time in the colon. The pocket-creation method (PCM) is a new technique in overcoming these difficulties of ESD in the treatment of colorectal lesions ≥3cm in size. But for larger lesions both the vascular structures and submucosal area to be dissected is larger. We investigated the efficacy of pocket creation tunneling method (PCM-t) in giant (≥5 cm) LSTs.

Aims & Methods: A total of 345 ESD procedures, which were performed in the esophagus, stomach, colorectum and duodenum between April 2012 and April 2015, were recorded prospectively before and after the procedure. 191 ESD procedures were performed in the colorectum. Lesions <5 cm in size and those removed with PCM were excluded from the study. The data of the rest 35 patients with lesion size ≥5cm were analyzed retrospectively. The patients were divided in to two groups; namely the ESD and PCM-t, according to the technique performed. The en-bloc and complete resection rates,complications, size of lesions, pathological results, length of procedure and dissection speed, and frequency of hemostatic forceps use in both groups were compared.

Results: Standard ESD was performed in 20 patients and PCM-t in 15 patients. There were no statistically significant differences between the two groups regarding age, gender, duration of procedure, size and type, endoscopic view, localization and pathological results of the lesions (p > 0.05).The dissection rate was higher in the PCM-t group and the frequency of hemostatic forceps use was less (p=0.046 and 0.044, respectively). En-bloc and complete resection rates were higher in PCM-t group and complication rate was less.

Abstract number: P0173

	Standard Group (n=20)	PCM-t Group (n=15)	p
Lesion size, (median;range),mm	58.5; 50-104	66; 51-170	0.364
Tissue size, (median;range),mm	68.5; 50-123	74; 58-198	0.131
Time of procedure, (median;range),min	104; 46-321	107; 47-540	0.987
Dissection speed, (median;range),mm2/min	26.6; 11-65.3	33.7; 22-78.2	0.046
Hemostatic Forceps Use	5;3-15	4;0-21	0.044
En-Bloc Resection, n(%)	18(90)	15(100)	0.319
Complete Resection, n(%) R0 Resection R1 Resection Rx Resection	18(90) 1(5) 1(5)	15(100) 0(0) 0(0)	0.451
Complication,n Delayed bleeding Perforation	0 1	1 0	0.241
Localization,n Rectum Sigmoid colon Descending colon Transverse colon Hepatic Flexura Ascending colon Ceacum	11 0 3 1 2 1 2	9 3 0 0 0 2 1	0.155
Pathology,n Carcinoma -Intramucosal -Sm1 invasion Tubular Adenoma Tubulovillous Adenoma Villous Adenom	11 10 1 1 5 4	7 0 0 0 7 1	0.46 5

Conclusion: The dissected lesion can completely block the lumen as the diameter of colon is small and generally the lesions are more vascular. This may lead to difficult dissection and a long procedure time.When the lesion diameter is large, dissection of the submucosal area as a tunnel helps in dissecting with control by providing a better notice of the vascular area.Using PCM-t in giant colorectal lesions can increase en-block resection rate, help in controlled dissection, decrease use of forceps besides decreasing the length of duration and increasing dissection rate.

Disclosure of Interest: None declared

P0174 ENDOSCOPIC SUBMUCOSAL DISSECTION IN COLORECTAL LESIONS: EXPERIENCE OF 191 CASES FROM A TERTIARY REFERENCE CENTER IN TURKEY

F. Aslan¹, Z. Akpınar¹, N. Ekinci², E. Alper¹, C. Çekiç¹, B. Ünsal¹

¹Gastroenterology, ²Pathology, Katip Celebi University Ataturk Training and Research Hospital, Izmir, Turkey

Contact E-mail Address: drfatihaslan@hotmail.com

Introduction: Endoscopic submucosal dissection (ESD) is a minimally invasive technique, providing en-bloc resection of premalignant lesions and early stage gastrointestinal (GI) cancers. This procedure is commonly used in Far East countries like Japan and Korea; however, it has come into use in western countries in recent years. Additionally, ESD is not as widely performed in the colorectum compared with gastric ESD. In the present study, we present our results of colorectal ESD procedures.

Aims & Methods: A total of 345 ESD procedures, which were performed in the esophagus, stomach, colorectum and duodenum between April 2012 and April 2015, were recorded prospectively before and after the procedure. Patient data were analyzed retrospectively. We began to perform colorectal ESDs after 30 gastric ESD procedures and proximal colon segment procedures were performed only after 15 rectal ESD procedures had been completed. The results of 191 ESDs performed in colon and rectum were analyzed retrospectively.

Results: In a total of 185 patients, 191 colorectal ESDs were performed. The overall en-bloc and complete resection rates were 90.1% and 88.5%, respectively. Histopathology revealed carcinoma in 80, adenoma in 108 and neuroendocrine tumor in 3 patients. Complete resection was not achieved in 8.4% patients with positive vertical border. Perforation occurred in 4 patients which were treated successfully with endoscopic clip without the need for surgery except for one patient with delayed perforation (Table). Although cover type knife was generally preferred during the first cases non-cover type knife was used for later procedures. Surgical treatment was performed in all patients with deep submucosal (sm2) invasion, however neoplasia was observed in none of these patients.Table.Demographic data and colorectal ESD results Lesion (N)=191

Abstract number: P0174

Gender, Male/Female, n	103/82
Age, years, mean (SD) (median; range)	62.16 (11.55) (63; 26-88)
Lesion size, mm, mean (SD) (median; range)	37.88 (22.72) (33; 7-170)
Tissue size, mm, mean (SD) (median; range)	45.52 (24.58) (40; 10-198)
Duration of procedure, min, mean (SD) (median; range)	78.49 (70.11) (61; 6-540)
Dissection speed, mm2/min, mean (SD) (median; range)	21.49 (13.92) (17.66; 1.74-79.55)
En-Bloc Resection , N (%)	172 (90.1)
Complete Resection, N (%) R0 Resection R1 Resection Rx Resection	169 (88.5) 16 (8.4) 6 (3.1)
Paris Classification, N (%) 1s 1s + 2a 2a 2a + 2c SMT	3 (1.6) 101 (52.9) 58 (30.4) 26 (13.6) 3 (1.6)
Adverse Events, N (%) Delayed bleeding Perforation	2 (1.0) 5 (2.6)
Localization, N (%) Rectum Sigmoid colon Descending colon Splenic Flexura Transverse colon Hepatic Flexura Ascending colon Cecum Ileocecal valve	86 (45.0) 31 (16.2) 14 (7.3) 6 (3.1) 8 (4.2) 18 (9.4) 13 (6.8) 11 (5.8) 4 (2.1)
Pathology, N (%) Carcinoma -Intramucosal -Sm1 invasion -Sm2 invasion Tubular Adenoma Tubulovillous Adenoma Villous Adenoma Serrated Adenoma Neuroendocrine tumor	80 (41.9) 61 (31.9) 3 (1.6) 16 (8.4) 16 (8.4) 68 (35.6) 14 (7.3) 10 (5.2) 3 (1.6)
Dysplasia, N (%) None Mild Moderate Severe	3 (1.6) 5 (2.6) 11 (5.8) 172 (90.1)

Conclusion: ESD is a safe and effective method to provide en-bloc and curative resection of premalign or malign colorectal lesions.

Disclosure of Interest: None declared

P0175 SALVAGE ENDOSCOPIC RESECTION OF SCARRED POLYPS AFTER FAILED PREVIOUS ENDOSCOPIC RESECTION ATTEMPT: SENSE STUDY

F. J. Q. Chedgy¹, R. Bhattacharyya¹, K. Kandiah¹, G. Longcroft-Wheaton¹, P. Bhandari¹

¹Gastroenterology, Queen Alexandra Hospital, Portsmouth, Portsmouth, United Kingdom

Contact E-mail Address: ferguschedgy@yahoo.co.uk

Introduction: Current standard of care for recurrent/residual polyps after previous endoscopic resection is surgery which can be associated with significant morbidity and cost.

Aims & Methods: This study analyses the outcomes of salvage endoscopic resection of polyps with severe scarring following a previously failed endoscopic resection. Prospective cohort study of patients referred to a Tertiary-centre for resection of scarred polyps with failed previous endoscopic resection attempts. Resection techniques: ESD knife & Snare combination (Knife Assisted Resection, KAR) or Snare & APC assisted resection (SAR).

Results: We identified 64 consecutive patients referred to us following a previously failed endoscopic resection attempt. All these patients had severely scarred polyps which were being considered for surgery at the referring centre. The mean polyp size 46mm (20-150mm). 83% were left-sided and 17% right–sided. 67% of resections were performed by KAR with mean polyp size 50mm. 33% of resections were by SAR with mean polyp size 38mm.

Referral to surgery: 2/64 for technically difficult so no attempt made, 5/64 for cancer.

Endoscopic follow up & cure: mean follow up of 3 years (range: 1-8 years), 97% overall cure rate which was the same for left and right sided lesions as well as KAR and SAR. The only complication was bleeding seen in 3 patients (4.6%).

Cost saving: Had all 64 patients been sent for surgery the total cost would have been £343,224. The total cost of the endoscopic approach, including the cost of patients requiring surgery, was £149,820 representing an average cost saving of £3021.94 per patient.

Conclusion: Severely scarred polyps due to failed previous endoscopic mucosal resection attempts can be successfully treated by experts. The techniques of KAR and SAR are equally effective when used for appropriate polyps. The complication rate is low. Further recurrence after first salvage resection can be treated successfully. Surgery can be avoided in most patients and an endoscopic approach is very cost effective. We would therefore, advocate an aggressive endoscopic resection strategy over surgery when dealing with severely scarred polyps.

Disclosure of Interest: None declared

P0176 COLON CLEANSING FOR COLONOSCOPY IN PATIENTS WITH IBD COLITIS: EFFICACY AND ACCEPTABILITY OF 2 LITER PEG VS 4 LITER PEG

G. Manes¹, P. Fontana², G. de Nucci¹, F. Radaelli³, C. Hassan⁴, S. Ardizzone⁵

¹Gastroenterology, G. Salvini Hospital, Garbagnate Milanese, Milano, Italy, Garbagnate Milanese, Milano, ²Gastroenterology, Sacco University Hospitla, Milano, ³Gastroenterology, Valduce Hospital, Como, ⁴Gastroenterology, Nuovo Regina Margherita Hospital, Roma, ⁵Gastroenterology, Fatebenefratelli Hospital, Milano, Italy

Contact E-mail Address: gimanes@tin.it

Introduction: Low-volume preparations are gaining attention for higher acceptability, but their use in IBD patients has never been evaluated. This study compares the efficacy, safety and tolerability of a 2L PEG solution plus bisacodyl with a 4L PEG solution in patients with ulcerative colitis.

Aims & Methods: This is a multicenter, randomized, single-blind, non-inferiority study. Adult outpatients with ulcerative colitis undergoing colonoscopy received either 2L PEG plus bisacodyl or 4L PEG. Bowel cleansing was assessed using the Ottawa Scale and rated as adequate if the score was ≤2 in each colon segment. Patient acceptance, satisfaction, and related symptoms were recorded.

Results: 211 patients were included. Overall, preparation was adequate in 80% patients without any differences between groups. Mean Ottawa scores for whole and right colon were similar in the two groups. As concern tolerability, 83% patients in 2L PEG bisacodyl arm and 44.8% in 4L PEG arm reported no/mild discomfort (p < 0.0001) and 94.3% and 61.9% expressed their willingness to repeat the preparation (p < 0.001). Palatability was better with 2L PEG-bisacodyl, whereas related symptoms occurred more frequently with 4L PEG. Regardless of preparation, split dosage was associated to better cleansing. Further predictors of poor cleansing were moderate/severe discomfort during preparation, and more than 6 hrs between end of preparation and colonoscopy. Extension and severity of colitis did not influence quality of preparation.

Conclusion: Low-volume PEG plus bisacodyl is not inferior to 4L PEG for bowel cleansing in IBD, but it is better tolerated and accepted by patients. The time interval from solution intake and colonoscopy is the most important factor affecting quality of cleansing also in IBD.

(ClinicalTrial.gov number NCT02248337).

Disclosure of Interest: None declared

P0177 COMPUTER-ASSISTED INSTRUCTION BEFORE COLONOSCOPY IS AS EFFECTIVE AS NURSE COUNSELLING, A CONTROLLED TRIAL

G. Veldhuijzen¹, M. Klemt-Kropp², C. Noomen², T. van der Ploeg³, J. Drenth⁴

¹Gastroenterology, Radboudumc, Nijmegen, ²Gastroenterology, Medical Center Alkmaar, ³Foreest Medical School, Alkmaar, ⁴Gastroenterology, Radboudumc, Nijmegen, Netherlands

Contact E-mail Address: Govert.Veldhuijzen@radboudumc.nl

Introduction: Better patient education prior to colonoscopy, for instance through nurse counselling, improves adherence to instructions for bowel preparation and probably leads to cleaner colons. We hypothesized that computer assisted instruction (CAI) supported by video and 3D animations improves the effectiveness of nurse counselling, with potential operational advantages.

Aims & Methods: To assess the effectiveness of CAI for patient education prior to colonoscopy in terms of bowel cleanliness and patient knowledge, comfort and anxiety.

We included patients >18 years who were referred for colonoscopy in an endoscopy unit in a general teaching hospital in the Netherlands. Exclusion criteria were illiteracy in Dutch and audiovisual handicaps. Patients were divided into two consecutive groups, one which received nurse counselling and one which received CAI, followed by a brief contact with a nurse shortly before colonoscopy. The CAI had been reviewed by expert endoscopists. For the main outcome measure, cleanliness of the colon during examination, data was collected using a physician questionnaire including the Ottawa Bowel Preparation Scale (OBPS) and the Boston Bowel Preparation Scale (BBPS). We assessed patient anxiety, patient comfort and general information using three questionnaires validated by expert consensus, which were issued after counselling or CAI and shortly before and after colonoscopy. We assessed knowledge of information provided earlier through a pre-colonoscopy test consisting of 10 questions. Statistical analyses were performed, including Mann-Whitney and T-test.

Results: We included 385 patients, 197 in the nurse counselling group and 188 in the CAI group. Overall response rates for the three patient questionnaires were 99%, 76.4% and 69.9% respectively. The physician questionnaire had an overall response of 60.8%. Baseline characteristics were similarly distributed among groups. Bowel cleanliness did not differ significantly between the two groups; on the OBPS, the counselling group scored 6.07 (SD 2.53) and the CAI group 5.80 (SD 2.90), and on the BBPS the scores were 6.54 (SD 1.69) and 6.42 (SD 1.62) respectively. Anxiety scores did not differ significantly. Patient comfort scores were significantly lower after CAI only. But in combination with a brief nurse contact comfort scores were significantly higher shortly before the colonoscopy. Scores on the knowledge test were similar, with 7.08 (SD 1.17) and 7.31 (SD 1.11).

Conclusion: CAI is a safe and practical modality for instructing patients before colonoscopy. This study found no difference in bowel cleanliness and patient knowledge with respect to the two groups. However, brief personal contact yielded significantly better patient comfort scores. We therefore recommend the combination of CAI with a brief nurse contact for daily practice.

Disclosure of Interest: None declared

P0178 SAFETY AND EFFICACY OF A NOVEL BALLOON SYSTEM FOR DIFFICULT COLONOSCOPY

H. Neumann¹, T. Rath¹, A. Nägel¹, M. Neurath¹, M. Vieth², K. Mönkemüller³

¹Department of Medicine I, University of Erlangen-Nuremberg, Erlangen, ²Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany, ³Basil Hirschowitz Endoscopic Center of Excellence, University of Alabama at Birmingham, Birmingham, United States

Contact E-mail Address: helmut.neumann@uk-erlangen.de

Introduction: Colonoscopy is the gold standard for colorectal cancer screening. However, total colonoscopy may be impeded by several factors, including extensive diverticulosis, elongated transverse colon, female gender, low body mass index, or prior abdominal or pelvic surgery.

Aims & Methods: Aim was to evaluate the safety and efficacy of a novel balloon system which will be introduced at UEGW 2015 for difficult colonoscopy. Therefore, patients (mean age 75 years; Range 21-78 years; 40% female) referred for colonoscopy after failure of previous colonoscopy were prospectively enrolled in a pilot cohort study whose primary end point was device safety. Other study endpoints included success rate and time of cecum intubation, withdrawal times, total procedure times, and success of therapeutic procedures.

Results: Among the enrolled patients one was excluded due to a technical problem of the device. Ileocolonoscopy was performed in all (100%) patients using the novel balloon-system without any complications. Cecal intubation rate was 100%. Mean times to reach the cecum, withdrawal, and total procedure times were 11.05 minutes, 15 minutes, and 32 minutes, respectively. All therapeutic endoscopic interventions that were required were performed without any complications. Success rate of therapeutic procedures was 100%.

Conclusion: The novel introduced balloon-system for difficult colonoscopy appears safe and effective to use. Final data will be presented at UEGW.

Disclosure of Interest: None declared

P0179 PROSPECTIVE 1:1 RANDOMIZED STUDY TO ASSESS THE PERFORMANCE CHARACTERISTICS OF COLORECTAL FULL SPECTRUM ENDOSCOPY (FUSE)

H. Neumann¹, G. Tontini¹, M. Vieth², T. Rath¹, M. Grauer¹, I. Gralnek³, M. Neurath¹

¹Department of Medicine I, University of Erlangen-Nuremberg, Erlangen, ²Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany, ³Department of Gastroenterology, Technion-Israel Institute of Technology, Haifa, Israel

Contact E-mail Address: helmut.neumann@uk-erlangen.de

Introduction: The newly introduced Full Spectrum endoscope (FUSE) provides a 330° field of view thereby potentially allowing endoscopists to see more anatomy of the colon as compared to standard forward viewing endoscopes (FVE). Recent data has indicated that FUSE significantly reduced adenoma miss rates.

Aims & Methods: The aim of this prospective randomized study was to assess the performance characteristics of FUSE in comparison to FVE. Therefore, patients were randomly assigned at a one-to-one ratio to undergo colonoscopy with FUSE or FVE after a previous sample size calculation. Performance characteristics including time to cecum, withdrawal time, total examination time, medication, patient and endoscopists’ satisfaction, and polyp detection rates were recorded.

Results: Among 109 patients, 19 patients were excluded (11 inadequate bowel preparation; 5 hemicolectomy, 2 stenosis, 1 severe inflammation). 90 patients were finally randomized at a 1:1 ratio to undergo FUSE or FVE. Time to cecum (minutes, mean ± SD) was 4.05 ± 0.68 minutes for FUSE and 5.48 ± 0.67 minutes for FVE (P < 0.001). Withdrawal times were 12 ± 4.16 minutes and 15 ± 4.28 minutes for FUSE and FVE, respectively (p <0.01). Total examination time was 16.30 ± 4.72 minutes in the FUSE group and 20.48. ± 4.39 minutes in the FVE group (p < 0.001). Sedation was less required in the FUSE group as compared to FVE (mean propofol dosage, 170 mg vs. 200 mg). Significantly more patients needed analgesia in the FVE group (meperidine; P = 0.002). Patient and endoscopists satisfaction were high throughout the cases and not different between both groups. Polyps were detected in 36% and 24% of patients in the FUSE and FVE group, respectively.

Conclusion: Advancement times of the scope to the cecum and withdrawal times were faster with the FUSE scope as compared to standard FVE. Satisfaction rates of patients and endoscopists were similar in both groups while patients needed more sedation and analgesia in the FVE group. Although more polyps were found in the FUSE group the study was not designed to compare adenoma detection rates between both groups.

Disclosure of Interest: None declared

P0180 RISK FACTORS FOR POSTPOLYPECTOMY BLEEDING AND ITS ASSOCIATION WITH HEPARIN BRIDGE THERAPY

H. Ishigami¹, M. Arai¹, K. Okimoto¹, D. Maruoka¹², T. Matsumura¹, T. Nakagawa¹, T. Katsuno¹, O. Yokosuka¹

¹Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, ²Clinical Research Center, Chiba University Hospital, Chiba, Japan

Contact E-mail Address: the-god-of-stone14@nifty.com

Introduction: Postpolypectomy bleeding (PPB) is the most common complication of colonic polypectomy. The risk of PPB is associated with increasing age, anticoagulation therapy, hypertension, large polyp size, proximal location, and polyp morphology. According to American Society for Gastrointestinal Endoscopy (ASGE) and Japanese Society of Gastrointestinal Endoscopy (JSGE) guidelines, for patients taking anticoagulants (e.g. warfarin), bridge therapy with unfractionated heparin (UFH) or low molecular weight heparin (LMWH) is recommended to reduce the risk of thromboembolic events during high-risk procedures like polypectomy. However, little is known about the risk of PPB with heparin bridge (HB) therapy. We investigated the association between HB therapy and PPB.

Aims & Methods: We retrospectively reviewed 1659 polypectomies performed on 906 patients from January 2007 to December 2014 at our institution. A total of 728 patients did not take any antithrombotic agents (control group), and 45 patients underwent colonic polypectomy while receiving HB therapy (HB group). We analyzed the risk factors for PPB related to both the patients and the polyps, and we determined the rate of PPB in the HB group.

Results: PPB occurred in 33 lesions (2.0%) of 30 patients (3.3%). Eleven of 30 (36.7%) PPB patients were in the HB group (p < 0.0001), and the incidence of PPB in the HB group was 24.4% (11 of 45 patients). Polyp size ≧10 mm (20 of 33 [60.6%] vs. 639 of 1626 [39.3%], p= 0.015), pedunculated polyps (12 of 33 [36.7%] vs. 288 of 1626 [17.7%], p =0.012), and location in the cecum (10 of 33 [30.3%] vs. 111 of 1626 [6.9%], p <0.0001) were significant risk factors for PPB. In the control group, size ≧10 mm, pedunculated polyps, and location in the cecum were also significant PPB risk factors (p = 0.0042, p = 0.014, and p = 0.0029, respectively), although in the HB group, these were not significant (p = 0.39, p = 1.0, and p = 0.053, respectively). PPB in small polyps (≧10 mm) was higher in the HB group (15.4%, 10 of 65 lesions) than in the control group (0.73%, 7 of 963 lesions) (p < 0.0001), as was the recurrent bleeding rate (27.3% [3 of 11 patients] vs 0% [0 of 15 patients], respectively) (p = 0.064).

Conclusion: HB therapy, polyp size ≧10 mm, pedunculated polyps, and location in the cecum are risk factors for PPB. The incidence of PPB was higher in the HB group, and PPB occurred even if the polyp size was small (≧10 mm).

Disclosure of Interest: None declared

P0181 THE VALIDITY AND SAFETY OF THE COLORECTAL ESD FOR THE LESIONS SPREADING TO THE APPENDICEAL ORIFICE

H. Chiba¹, D. Kurihara¹, T. Suto¹, N. Kawano¹, M. Kaai¹, K. Ashikari¹, S. Seki¹, A. Takahashi¹, I. Tomonori¹, T. Morohashi¹, T. Goto¹

¹Gastroenterology, Omori Red Cross Hospital, Tokyo, Japan

Contact E-mail Address: h.chiba04@gmail.com

Introduction: Colorectal ESD has not been widely performed for colorectal tumors because of the high frequency of complications. Especially, ESD for the lesions spreading to the appendiceal orifice needs higher skill because of the confrontation to the muscle layer, narrow working space or spontaneous fibrosis. It is still unknown about the validity or effective strategy for these lesions.

Aims & Methods: 163 consecutive cases who underwent ESD in Omori Red Cross Hospital from 2012 April to 2015 March were analyzed. We use needle knife (Flex or Dual knife, Olympus Co Tokyo, Japan) for colorectal ESD. The main strategy for the lesions in the appendiceal orifice was shown as follows; we do the first injection from the tip of the vermiform appendix so that the tumor does not sink to the end of the vermiform appendix. This first injection should be minimum volume, and we make an enough endpoint around the appendiceal orifice as soon as possible. After this, we can continue ESD while using a counter traction of the gravity. We assessed the clinical findings and outcomes of ESD for the 6 lesions spreading to the appendiceal orifice (group A), compared to the other 157 lesions as control (group B).

Results: Mean age, sex, antithrombotic agents and past history were similar between two groups and there was no case of post appendicitis in group A. All ESD in group A was performed by one experienced endoscopist (≧150 colorectal ESD cases).Tumor shape was Is0/LST-G5/LST-NG1 in group A, and Is8/LST-G58/LST-NG84/SMT4 in group B, respectively. In addition, tumor size, specimen size, the area of the resected specimen, rate of en-bloc resection, and rate of curative resection were also similar: 35.8mm, 41.8 mm, 1187.9 mm², 6/6(100%), and 6/6(100%) in group A, and 28.4mm, 36.8mm, 1022.7mm², and 156/157 (99.4%) in group B, respectively. The number of mild or sever fibrosis was more often in group A (non; 3, mild; 3) than in group B (non; 127, mild; 25, severe; 5) (p=0.077), but the mean operation time (group A: 42.5min, group B: 42.9min) was about the same. Pathological findings were adenoma2/M3/SM-slight 1 in group A, and adenoma71/M73/SM-slight3/SM-massive6/SMT4 in group B, respectively. The number of post bleeding or perforation was no case in group A and 2 perforations in group B. After ESD, WBC(/μl), CRP(mg/dl), a number of having a high fever(≧38°C), and taking a painkiller had no significant difference.

Conclusion: ESD for the lesions spreading to the appendiceal orifice was safe and there were no significant differences of outcomes, compared to the lesions in the other positions. Our strategy for these lesions will be appropriate. However, the existence of the spontaneous fibrosis around appendiceal orifice is not a little and the working space is very narrow, so we have to understand the characteristics of the appendiceal orifice.

Disclosure of Interest: None declared

P0182 PITFALL OF PIT PATTERN DIAGNOSIS AND MAGNIFYING ENDOSCOPY WITH NARROW BAND IMAGING -PREDICTION OF THE DEPTH OF SUB MUCOSAL INVASION FOR COLORECTAL NEOPLAS

H. Osumi¹, Y. Tamegai¹, T. Kishihara¹, A. Chino¹, M. Igarashi¹

¹Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

Contact E-mail Address: hiroki.osumi@jfcr.or.jp

Introduction: In Japanese Society for Cancer of the Colon and Rectum guidelines 2014, the intramucosal or superficial submucosal (depth of invasion <1000 μ m:T1a) invasion is important to determine appropriate for ESD. On the other hand, size and macroscopic type both do not matter. So it is important for us to evaluate the depth of submucosal invasion because there have been reports of significantly increased risk factors for lymph node metastasis of early colorectal cancers in cases where the lesions invaded the deep submucosa (depth of invasion ≥ 1,000 μ m:T1b). When we evaluate the depth of invasion for colorectal cancer, we usually use pit pattern classification and magnifying narrow band imaging (NBI) adding white light observation and magnifying chromo-endoscopy.

Aims & Methods: The aim of this study is to evaluate diagnostic accuracy in estimating the depth of submucosal invasion of colorectal neoplasms using both pit pattern classification and NBI, and to extract endoscopic features for misdiagnosis patients. We enrolled the 522 patients who performed colorectal ESD from January 2011 to December 2014. Among them, 286 patients (57.3%, 164 men, 42.7%, 122 women, Median age ±SD: 66 ±11.3 years) that we could confirm type V pit pattern were enrolled for this study. Type V pit patterns include areas with irregular crypts (type V_I) and areas of apparent non-structure (type V_N). Type V_I pit patterns are further subdivided into areas of mild irregularity (type V_I mild) and areas of severe irregularity, which exhibit destroyed and damaged pits (type V_I severe). We evaluated the ability of differential diagnosis between Tis-T1 cancer and T1b cancer using type V pit pattern and NBI, and extract endoscopic features for misdiagnosis patients.

Results: In macroscopic type, polyploid type was 31.1% (88/286), and depressed or laterally spreading type were 68.9% (LST-G:106?LST-NG and depressd:92). In the relationship between type V pit pattern and the depth of invasion, sensitivity, specificity, and accuracy were 96.0%, 33.3%, and 88.1%, respectively. On the other hand in the relationship NBI and the depth of invasion, sensitivity, specificity, and accuracy were 89.4%, 32.3%, and 82.5%, respectively. Endoscopic features of misdiagnosis patients of type V mild shrunk in size of villous component, depressed area, and more than 30mm in max diameter. Furthermore, expansiveness, constitutive of the focal fold, and white spots in the polyploid type appeared with higher frequency than in the depressed or laterally spreading type. In contrast, the frequency features of a large nodule in the depressed lesion or laterally spreading type was higher than in the polyploid type. For the patients of type V severe, 5 patients had loss of dyeing and this was the factor of over diagnosis. The remaining 5 patients high frequency of endoscopic features were severe redness, elevation, depressed component, and the area of type V severe within 5mm in diameter.

Conclusion: Endoscopic findings suggest that there are some limitations of the diagnosis of the depth of submucosal invasion for colorectal cancer using pit pattern classification and NBI. We should utilize the findings of the lesions invaded with deep submucosa in the white light and chromo-endoscopic observation and evaluate submucosal fibrosis of the cancer when performing ESD.

Disclosure of Interest: None declared

P0183 A VISIBILITY STUDY USING NARROW BAND IMAGING IN THE COLORECTAL FLAT AND DEPRESSED LESIONS

H. Nakamura¹, H. Ikematsu¹, S. Osera¹, K. Shinmura¹, T. Hombu¹, K. Takashima¹, M. Imajo¹, T. Kadota¹, T. Katoh¹, H. Morimoto¹, Y. Yoda¹, Y. Oono¹, M. Kojima², A. Ochiai², K. Kaneko¹

¹Department of Gastroenterology, Endoscopy Division, ²Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Japan

Contact E-mail Address: hirosnak@east.ncc.go.jp

Introduction: Background: In conventional observation using white light, miss rate of adenoma was 10–30% through colonoscopy. It is difficult to detect flat lesions, especially laterally spreading tumors of non-granular type (LST-NG) and depressed lesions with higher malignant potential. In many detection studies for all colorectal lesions including polypoid, flat, and depressed lesions, no significant difference as seen in detection rate between narrow band imaging (NBI) and white light imaging, however, there have been no reports regarding visualization of LST-NG and depressed lesion in NBI observation.

Aims & Methods

Aim: To investigate the visibility of LST-NG and depressed lesions by using NBI.

Methods: We intended consecutive patients with LST-NG and IIc lesions that were endoscopically or surgically resected in our hospital between August 2011 and July 2013. These lesions were classified into four groups as followed: “Brownish area (BA)”, “Brown of only margins (O-ring sign)”, “Same color as normal mucosa (SC)” and “Whitish area (WA)” by appearance of NBI, and reveal each ratio. Furthermore, we compared pathological findings in individual groups of LST-NG and IIc lesions.

Results: Result: A total of 19 IIc lesions and 180 LST-NG lesions were analyzed. In IIc lesions, BA was 6 lesions (31.5%), O-ring sign was 11 lesions (57.9%), SC was 1 lesion (5.3%) and WA was 1 lesion (5.3%). In LST-NG lesions, BA was 120 lesions (66.7%), O-ring sign was 26 lesions (14.4%), SC was 34 lesions (18.9%) and WA was no lesions. The pathological findings of IIc lesions as followed: in BA, 1 lesion (16.7%) of high grade dysplasia (HGD), and 5 lesions (83.3%) of low grade dysplasia (LGD). In O-ring sign, 2 lesions (18.1%) of invasive cancer, and 9 lesions (81.9%) of LGD. In SC and WA, LGD were 1 lesion (100%). The pathological findings of LST-NG lesions as followed: in BA, 25 lesions (20.8%) of invasive cancer, 45 lesions (37.5%) of HGD, and 50 lesions (41.7%) of LDG. In O-ring sign, 8 lesions (30.8%) of invasive cancer, 4 lesions (15.4%) of HGD, and 14 lesions (53.8%) of LGD. In SC, 3 lesions (8.8%) of invasive cancer, 8 lesions (23.6%) of HGD, and 23 lesions (67.6%) of LGD.

Conclusion: Conclusions: Since most of IIc lesions were visualized as brown by NBI, there would be clinical benefit for the visibility. On the other hands, approximately 20% of LST-NG lesions were recognized in same color as surround normal mucosa, so the visibility was inferior to that of IIc lesions.

Disclosure of Interest: None declared

P0184 USEFULNESS AND SAFETY OF COLD SNARE POLYPECTOMY FOR REMOVING COLONIC POLYPS IN JAPANESE PATIENTS

H. Noda¹, N. Ogasawara¹, H. Hoshino¹, T. Nagoya¹, A. Koshino¹, Y. Kondo¹, Y. Ito¹, S. Izawa¹, M. Ebi¹, Y. Funaki¹, M. Sasaki¹, K. Kasugai¹

¹Gastroenterology, Aichi Medical University School of Medicine, Nagakute, Japan

Contact E-mail Address: bisaipan@aichi-med-u.ac.jp

Introduction: Colorectal cancer is a major health problem worldwide. Polypectomy of small colonic polyps has been an effective procedure for reducing the risk of colon cancer development by interrupting the progression of adenoma to carcinoma. Cold snare polypectomy (CSP) which can treat small colonic polyps without electrocautery has been recently reported to be useful for removing small colonic polyps in European countries, and CSP has become one of the common procedures for resecting colonic polyps. In Japan, CSP has been gradually utilized although endoscopic mucosal resection (EMR) has been a most common method for removing small colonic polyps. However, there has been few reports regarding the usefulness and safety of CSP in Japanese patients.

Aims & Methods: To verify the usefulness of CSP, we analyzed the complete resection rate and the complication between EMR and CSP. Subjects were 423 consecutive patients with 1010 lesions (ranges of polyp sizes, 3 mm-15 mm; average of polyp size, 6.8 mm; macroscopic type, Is or Isp) resected by EMR, and 106 patients with 175 lesions (ranges of polyp sizes, 3 mm-10 mm; average of polyp size, 5.0mm; macroscopic type, Is or Isp) resected by CSP at Aichi Medical University School of Medicine between May 2014 and February 2015. Moreover, 175 lesions resected by CSP were divided into two groups; 58 lesions resected by CSP using short snare (diameter of the snare, 13 mm) and 117 lesions resected by CSP using long snare (diameter of the snare, 27 mm). The complete resection rate was histologically compared between the two groups.

Results: There was no significant difference in complete resection rate between EMR (99.5%) and CSP (99.4%). There were no significant difference related with complications such as perforation and post-operative bleeding between EMR (perforation: 0, post-operative bleeding: 2) and CSP (perforation: 0, post-operative bleeding: 0). Histological examination revealed that complete resection rate of CSP using short snare (60.3%) is significantly higher than that of CSP using long snare (33.7%) (p<0.05). There were no significant difference in complications between CPS using short-snare and CPS using long-snare.

Conclusion: CSP is a safe method for removing colonic polyps without complication. The complete resection rate in CPS using short snare is significantly higher than that in CPS using the long snare. Our study demonstrates that the short snare is considered to be useful for removing colonic polyps compared with the long snare in CPS. Thus, CSP using the short snare should become widely applicable to Japanese patients.

Disclosure of Interest: None declared

P0185 DEVELOPMENT OF NOVEL TECHNIQUE FOR IDENTIFICATION OF COLONOSCOPE SHAPE USING ULTRATHIN SHAPE SENSOR: A PILOT STUDY

I. K. Yoo¹, H. J. Chun¹, S. H. Kang¹, J. H. Lee¹, S. H. Kim¹, J. M. Lee¹, H. S. Choi¹, E. S. Kim¹, B. Keum¹, Y. T. Jeen¹, H. S. Lee¹, C. D. Kim¹

¹Department of Internal Medicine, Korea University College of Medicine, Institute of Gastrointestinal Research and Medical Device Development, Division of Gastroenterology, Seoul, Republic of Korea

Contact E-mail Address: ikyoo82@hanmail.net

Introduction: During colonoscopy, procedural completion, accuracy, comfort, and safety are important factors. Uncontrolled looping of the colonoscope shaft during insertion can cause abdominal pain and could lead serious complications. Scope guided endoscopy using ultrathin shape sensor can reduced unnessessory tactile pressure or torque.

Aims & Methods: The aim of this study is to simulate 3D structure of colonoscope using ultrathin shape sensor. We conducted a prospective pilot study. Three-dimensional (3D) shape of the colonoscope shaft was obtained by using ultrathin shape sensor of fiber Bragg gratings. It detect strains and bending angles and provides real-time continuous 3D imaging of the colonoscope without radiation hazard. We reconstructed the shape of colonoscope and measured bending curvature and error of tip position.

Results: Total 10 patients underwent colonoscopy using ultrathin shape sensor. The results show that the shape sensor is reliable at a maximum bending curvature of 80mm⁻¹. The average tip position error was 1.722 ± 1.678mm, which corresponds to 1.50 ± 1.46% of the total length of the sensor.

In this approach, the endoscopists performance may enhanced by providing using a kinetic model that provides information such as the shape of the scope, direction of the colon and forces.

Conclusion: Scope guided endoscopy using FBG sensor can be successfully used to display colonoscope configuration by reconstruction of the high curvature bending and low tip position error. This Flexible, thin and almost weightless shape sensor would be a novel technique for identification of colonoscope shape.

Disclosure of Interest: None declared

P0186 PROSPECTIVE, OBSERVATIONAL STUDY TO EVALUATE THE ACCURACY OF ELECTRONIC ISCAN CHROMOENDOSCOPY TO PREDICT HISTOLOGY OF COLORECTAL LESIONS IN NON-EXPERT HANDS

N. Vallejo-Senra¹², M. Díaz-López¹², R. Ferreiro-Iglesias¹², J. E. Domínguez-Munoz¹²

¹Foundation for Research in Digestive Diseases, ²University Hospital of Santiago de Compostela, Santiago de Compostela, Spain

Contact E-mail Address: info@fienad.org

Introduction: Accurate detection and characterization of colorectal lesions are important for optimal treatment and follow-up strategies. Electronic chromoendoscopy may be helpful in this setting, but scientific evidence is inconclusive. The usefulness of chromoendoscopy may differ according to the expertise of endoscopists. We hypothesized that i-Scan, the electronic chromoendoscopy available in Pentax endoscopes, improves the characterization of colorectal lesions in non-expert hands.

Aims & Methods: Aim of the present study was to assess the impact of different iScan profiles for the accurate characterization of colorectal lesions in non-expert hands.

Material and methods: A prospective, observational study of colorectal lesions detected in patients referred to our Endoscopy Unit for diagnostic colonoscopy from February to April 2015 was designed. Three experienced endoscopists collected four images from every lesion by applying HD-white light (HDWL) and three different iScan profiles (iScan1, iScan2 and iScan3), respectively before endoscopic removal for histological evaluation. Total collected images from all lesions were presented unlabeled in a randomized order to a young staff member with a two years’ experience in diagnostic and therapeutic endoscopy, and with a limited experience in advanced imaging, for predicting histological diagnosis. The accuracy to predict histology with the different iScan profiles compared to HDWL was calculated according to the size of the lesions. The prediction confidence was also evaluated and classified as low and high. Statistical analysis was performed using the chi-square test and Fisher exact test, as appropriate.

Results: A total of 444 images from 111 lesions were analyzed. Final histological diagnosis was adenoma in 73 cases and serrated lesions in 38 cases. Global accuracy for predicting histology increased from 69.4% with HDWL to 85.6% with iScan (p < 0.05). Accuracy was similar with any of the three iScan profiles (75.7%, 80.2% and 82.9% for iScan 1, 2 and 3, respectively) (n.s.). For non-serrated adenomas, accuracy to predict histology was 57.5% for HDWL compared to 82.2% with iScan (p < 0.05). Again, no statistical difference was observed among different iScan profiles, although accuracy tended to be higher with iScan3 (69.8%, 76.7% and 79.4% for i-Scan1, 2 and 3, respectively) (n.s.). Accuracy for serrated lesions was equal with HDWL and i-Scan (92.1% in both cases). Usefulness of iScan was greater for predicting histology in case of diminute and small lesions (19.3% and 11.9% diagnostic improvement with regard to the accuracy with HDWL, respectively) (p < 0.05). iScan also allowed to increase significantly the prediction confidence, and high prediction confidence was more frequent with iScan (78.4%) than with HDWL (51.3%) (p < 0.05).

Conclusion: i-Scan allows improving significantly the accuracy of optical diagnosis of colorectal lesions compared to HDWL in non-expert hands. This is mainly true for diminute and small adenomatous lesions. iScan also helps to increase the prediction confidence of these lesions.

Disclosure of Interest: None declared

P0187 THE FACTORS ASSOCIATED WITH COMPLETE ENDOSCOPIC RESECTION OF COLORECTAL ADENOMAS IN EXPERTS AND FELLOW-TRAINEES

J. M. Choi¹, C. Lee², S.-J. Koh³, J. P. Im¹, J. W. Kim³, J. S. Kim¹, B. G. Kim³, K. L. Lee³

¹Internal medicine, Seoul National University Hospital, ²Internal medicine, Seoul National University Hospital Healthcare System Gangnam Center, ³Internal medicine, Seoul National University Boramae Hospital, Seoul, Republic of Korea

Contact E-mail Address: skyjimin@hanmail.net

Introduction: The complete removal of adenomatous polyps is important for reducing the incidence and mortality of colorectal cancer. However, little information is available on the rate of incomplete polypectomy for intermediate sized lesions (5–20 mm) in clinical practice and on the affecting factors, and there are no guidelines addressing the issue of incomplete resection.

Aims & Methods: The aims of this study were to identify factors affecting the completeness of colonoscopic polypectomies and to evaluate the experience level of fellows who achieve competence compared with that of experts. Medical records of the patients who underwent at least one polypectomy for an adenomatous polyp at a single tertiary hospital between March 2011 and February 2013 were retrospectively reviewed. The lateral and deep margins of the resected polyps were evaluated to check the resection completeness.

Results: A total of 3,671 adenomatous polyps from 1,945 patients were included. Of these polyps, 1,591 (43.3%) were removed by three experts and 2,080 (56.7%) were removed by seven fellows. In the expert-treated group, polyp size ≥ 20 mm (odds ratio [OR] 3.07, 95% confidence interval [CI] 1.87-5.05, P < 0.001), right-sided location (OR 1.35, 95% CI 1.09-1.67, P = 0.006), and sessile type (OR 1.67, 95% CI 1.10-2.54, P = 0.017) was associated with incomplete resection. In the fellow-treated group, not only polyp characteristics (right-sided location [OR 1.41, 95% CI 1.18-1.69, P < 0.001]), but the cumulative number of procedures was also related to resection completeness. After 300 consecutive polypectomies, the complete resection rate of the fellows was comparable to that of the experts.

Conclusion: In the fellow-treated group, the level of procedure experience was closely associated with the outcome of colonoscopic polypectomy. Meticulous attention is critical to ensure the completeness of polypectomies performed by trainee endoscopists during the training program.

Disclosure of Interest: None declared

P0188 THE NICE, SANO AND WASP CLASSIFICATION IN SMALL COLONIC POLYPS EVALUATED WITH BLUE LASER IMAGING (BLI)

J. Dreanic¹, R. Coriat¹, S. Leblanc¹, F. Prat¹, V. Abitbol¹, M. Dhooge¹, M. Camus¹, M. Barret¹, B. Terris², S. Chaussade¹

¹Gastroenterology and endoscopy unit, ²Anatomopathology, Hopital Cochin - APHP, Paris, France

Contact E-mail Address: johann.dreanic@cch.aphp.fr

Introduction: The accuracy in the differentiation of colonic polyps would allow a “resect and discard” strategy for small colonic lesions. Recently, the ESGE suggested “that virtual chromoendoscopy can be used for real-time optical diagnosis of diminutive (<5 mm) colorectal polyps to replace the histopathological diagnosis”. Blue Laser Imaging (BLI), is a new endoscopic system (Fujifilm-Japan) associated with magnification, which can potentially further improve the differentiation of polyps. The aim of this study was to measure the diagnostic accuracy of polyp assessment (adenomatous versus hyperplastic) in small (6-9mm) and very small polyps (≤5mm), to allow a “resect and discard strategy” predict using BLI and zoom magnification.

Aims & Methods: Colonic polyps <10 mm were prospectively included in the study. Each polyp was evaluated with white-light, standard BLI, BLI-bright, with and without magnification (Zoom). Photos and video were performed for each polyp. Expert endoscopists reviewed all pictures and videos blindly, and classified polyps using size and the Paris, NICE, WASP and Sano classifications. Histological findings were correlated with clinical and endoscopic findings. Polyps were classified according the histopathological diagnosis between neoplastic lesions (adenoma n=46, Sessile Serrated Adenoma SSA/Ps n=4, and no invasive carcinoma) and non-neoplastic lesions (hyperplastic polyps n=11 and polypoid expansion of normal colonic mucosa n=15).

Results: A total of 76 lesions <10mm (n=33 of 6-9mm; n=43 of ≤5mm) were detected in 29 patients, and their median size was 5mm (IQR 3-7). Morphologies of the lesions were: 19 polypoid (0-I) and 57 slightly elevated (0-IIa). No slightly depressed without ulcer lesion (0-IIc) was observed. Pathological type of the polyp was predicted and polyp management decided upon for all 76 detected lesions. Polyps’ location was splenic flexure to cecum (proximal colon) and rectum to descending colon (distal colon) in 56% and 44% respectively. The overall sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy of BLI with magnification for the endoscopic diagnostic of neoplastic polyps were 0.88 (95% CI = 0.76-0.95), 0.58 (95% CI = 0.37-0.77), 0.80, 0.71 and 88%, respectively. Diagnostic accuracy of in vivo polyp assessment in 6-9mm and ≤5mm polyps were 92% and 83% respectively. Considering the adenoma detection, the accuracy of the NICE, Sano and WASP classifications was 64%, 64% and 92% (p=0.0013) respectively.

Conclusion: At the era of BLI and zoom magnification, small polyps identification using NICE and Sano classifications was not sufficient to allow a “resect and discard” strategy. The 90% agreement in assignment of post-polypectomy surveillance intervals recommended by the ESGE was not reached with NICE and SANO classifications. The diagnostic accuracy using the WASP classification is a promising technique to pass the 90% cut-off identified by the ESGE.

Disclosure of Interest: None declared

P0189 OPTICAL DIAGNOSIS OF COLONIC POLYPS: WHICH CLASSIFICATION SHALL WE USE AT THE EDGE OF THE BLUE LASER IMAGING (BLI) TECHNIQUE? THE WASP AND THE SANO CLASSIFICATION’ ACCURACY

J. Dreanic¹, R. Coriat¹, S. Leblanc¹, F. Prat¹, V. Abitbol¹, M. Dhooge¹, M. Camus¹, E. Sion¹, M. Barret¹, S. Chaussade¹

¹Gastroenterology and endoscopy unit, Hopital Cochin - APHP, Paris, France

Contact E-mail Address: johann.dreanic@cch.aphp.fr

Introduction: Accurate endoscopic differentiation of colonic polyps would allow resect and discard strategy for small colonic lesions. Blue Laser Imaging (BLI), a new endoscopic system has been validated to detect adenoma. The accurate endoscopy differentiation remained a challenge and new classifications have been developed to better identify adenoma from hyperplastic polyps. Recently, a classification system based on narrow band imaging (NBI) was validated for endoscopic differentiation of small and diminutive adenomas, hyperplastic polyps and Sessile Serrated Adenoma/polyps (SSA/Ps): the Workgroup serrAted polypS and Polyposis (WASP) classification. In addition, the SANO classification was validated in the same conditions using the pit pattern and the vascularization of the lesion. We herein stressed the WASP and the SANO classifications in optical diagnosis polyps using BLI and magnification.

Aims & Methods: 117 colonic polyps were studied in 45 patients in real-life colonoscopy, and prospectively included in the study. Each polyp was evaluated with white-light, standard BLI, BLI-bright, with and without magnification (Zoom). Experts endoscopists reviewed all pictures and videos blindly using WASP and Sano classifications. Polyps were classified according the histopathological diagnosis between adenoma (n=72), hyperplastic polyps (n=13), SSA/Ps (n=14), polypoid expansion of normal colonic mucosa (n=15) or invasive lesion (n=3). Histological findings were correlated with clinical and endoscopic findings. The diagnosis accuracy was evaluated considering histology, size, WASP and SANO classifications. A discrepancy between SANO and WASP classification was considered as the most advanced type of lesions.

Results: 117 polyps were resected by endoscopic submucosal resection (EMR) with a mean size of 12.8mm (1–60mm). Polyps location was splenic flexure to cecum (proximal colon) and rectum to descending colon (distal colon) in 57% and 43% respectively. The overall sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy of BLI with magnification using WASP classification for the endoscopic diagnostic of colorectal adenomas were 0.76 (95% CI = 0.66-0.85), 0.42 (95% CI = 0.25-0.63), 0.80, 0.36 and 76%, respectively. The overall sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy of BLI with magnification using SANO classification for optical diagnosis of advanced polyps were 0.91 (95% CI = 0.84-0.96), 0.67 (95% CI = 0.51-0.81), 0.86, 0.78 and 90%, respectively. The diagnostic accuracy of SANO and WASP classifications to predict SSA/Ps were 79% and 85%, respectively. Neither SANO nor WASP classifications were superior to detect SSA/Ps from adenoma (p = 0.82).

Conclusion: BLI and magnification are advanced endoscopic images that challenges optical diagnosis. SANO classification permits better endoscopic differentiation of small adenomas and non-neoplastic lesions than WASP classification. We observe a trend to better optical diagnosis of SSA/Ps by WASP classification. Acquisition of basic knowledge in BLI and magnification endoscopy could permit to improve endoscopic optical diagnosis of SSA/Ps using the new WASP classification.

Disclosure of Interest: None declared

P0190 CONSTIPATION; TO SCOPE OR NOT TO SCOPE? THAT IS THE QUESTION: A LARGE DISTRICT GENERAL HOSPITAL STUDY

J. Segal¹, C. Kanagasundaram¹, A. Vaziri¹

¹Gastroenterology, Lister Hospital, Stevenage, United Kingdom

Contact E-mail Address: jonathansegal@doctors.org.uk

Introduction: The European Society of Gastrointestinal Endoscopy and the British Society of Gastroenterology offer no specific guidelines on performing colonoscopy for constipation. The American guidelines advise to colonoscope those with constipation if new onset and over 50 years of age without prior bowel screening or in those with other alarm features (1). In Two US-Based Population retrospective case control studies, one suggested constipation had an increase Odds Ratio of 2.36 for colorectal cancer in those with bowel opening less than 3 times a week (2). The other study suggesting an increase Odds Ratio of 2.0 if needed laxatives 12-51 times in a year to 4.4 if laxative use was greater than 52 times in a year (3). A meta analysis of 8866 patients found that constipation as a primary indication was associated with colorectal cancer in 5.2% of patients which had a lower odds ratio of 0.56 when compared with other indications (4).

Aims & Methods: To determine if performing endoscopy in patients with constipation could detect cancers. All colonoscopies and flexible sigmoidoscopies performed for “ constipation” between January 2012 and December 2014 at the East and North Hertfordshire NHS trust were looked at using an endoscopy database. Cancer pick-up rate in this cohort was assessed with histology followed up following the procedure for confirmation of cancers. Cancer detection rates were then compared with the 4 most common other indications for colonoscopy at the NHS trust. Two tailed T tests were used to compare cancer detection rates with p value set at (<0.05).

Results: There were 298 endoscopies performed (165 Colonoscopies, 133 Flexible Sigmoidoscopies). There were 5 new cancers found on colonoscopy (3%) and 6 cancers found on flexible sigmoidoscopy (4.5%). When compared to the other top 4 indications for undergoing a colonoscopy there was no significant differences in cancer detection rate at (p < 0.05). “Diarrhoea” had a cancer detection rate of 0.8% which was significantly lower than for constipation detection rates. 3 New cancers were found with constipation as the primary indication with 5 cancers found for constipation with an abnormal CT scan.

Conclusion: As an indication for endoscopy, the indication “Constipation” remains a contentious issue without clear guidelines of when it is appropriate to scope. Our study has highligted that constipation as an only indication can still yield cancers as a rate similar to other important indications. This study has also highlighted the importance of imaging in those that are constipated. In those presenting with constipation a non invasive test first such as a CT scan to help rule out significant pathology.

Disclosure of Interest: None declared

P0191 STARTING ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) IN CLINICAL PRACTICE: A MODEL TO PREDICT THE NEED FOR A P-EMR

J. C. Marín-Gabriel^1,2, J. B. Díaz-Tasende¹², P. Cancelas-Navía³, S. Rodríguez-Muñoz¹, A. J. del Pozo-García¹, M. Pérez-Carreras¹, M. Alonso-Riaño⁴, Y. Rodríguez-Gil⁴, G. Castellano-Tortajada⁵

¹Department of Gastroenterology. Endoscopy Unit., Hospital Universitario 12 de Octubre, ²Department of Gastroenterology. Endoscopy Unit., Hospital Universitario Madrid Norte Sanchinarro, ³Department of Clinical Epidemiology, ⁴Department of Pathology, ⁵Department of Gastroenterology, Hospital Universitario 12 de Octubre, Madrid, Spain

Contact E-mail Address: josecarlos.marin@salud.madrid.org

Introduction: To improve the quality of ESD outcomes with the initial cases, it is crucial that factors predicting the need to end the procedure with a piecemeal endoscopic mucosal resection (pEMR) are evaluated.

Aims & Methods: The aim of our study was to prospectively assess what factors were associated with changing the initially planned ESD to pEMR and to develop a predictive model to anticipate the need for a piecemeal resection. We prospectively enrolled the first 122 cases referred for an ESD from September 2008 to April 2015.

Results: Endoscopic treatment was aborted in five cases. Finally, 117 lesions were included in the intention-to-treat analysis (95.9%). A pEMR was necessary in 40 (34.2%). Factors significantly associated with the need for a pEMR were: experience ≤ 40 ESDs (OR: 4.01; IC 95%: 1.77 – 9.06; p= 0.001), location out of the stomach (OR: 3.93; CI 95%: 1.55 – 9.63; p= 0.003), procedure time > 180 minutes (OR: 2.62; CI 95%: 1.16 – 5.92; p= 0.03) and size > 3 cm (OR: 5.15; CI 95%: 2.24 – 11.82; p<0.0001). In the logistic regression model, the factors independently associated with changing technique to a pEMR were: size of the lesion > 30 mm (OR: 4.80; CI 95%: 1.81 – 12.72; p= 0.002) and experience ≤ 40 ESDs (OR: 5.98; CI 95%: 2.18 – 16.42; p= 0.001). The value of the area under the ROC curve of the predictive model for a pEMR [logodds= 1.87 x (size > 3 cm) + 1.66 x (first 40 cases) + 1.07 x location out of the stomach – 2.90] was 0.81 (CI 95%: 0.73 – 0.89). A cut-off point of ≥ 0.34 for predicting pEMR showed the following diagnostic performance: sensitivity: 82.5% (CI 95%: 81.2 – 83.8); specificity: 70.1% (CI 95%: 69.4 – 70.8).

Age (mean ± SD)	69.8 ± 11.9
Male / Female n;%	67 / 50 (57.3 / 42.7)
Tumor location n; %
Esophagus	1 (0.85)
Stomach	42 (35.9)
Rectum	45 (38.4)
Colon	29 (24.8)
Mean tumor size, mm (mean ± SD)	31.6 ± 16.1
En bloc resections (n; %)	77 (65.8)
Piecemeal resections (n; %)	40 (34.2)
Histopathology (n; %)
Mucosal low grade neoplasia	31 (26.5)
Mucosal high grade neoplasia	71 (60.7)
Curative submucosal invasion	3 (2.5)
Non-curative submucosal invasion	7 (0.6)
Other (subepithelial tumors, carcinoids…)	5 (4.3)
Procedure time (mean ± SD)	190 ± 82
Delayed bleeding (n;%)	12 (10.3)
Perforations (n;%)	17 (14.5)

Conclusion: A scoring system combining the size and location of the lesion and the experience in ESD provided good diagnostic performance to predict the need for a p-EMR.

Disclosure of Interest: None declared

P0192 EFFECTIVENESS OF A SOFTWARE APPLICATION IN IMPROVING APPROPRIATENESS OF COLONOSCOPY PRESCRIPTION

J. Díaz-Tasende¹, J. C. Marín-Gabriel¹, P. Cancelas-Navia¹, P. Ruiz-López², J. Ferrándiz-Santos³, S. Rodríguez-Muñoz¹, M. Pérez-Carreras¹, F. Sánchez-Gómez¹, A. Del Pozo-García¹, G. Castellano-Tortajada¹

¹Gastroenterology, ²Quality and Patient^¨s Safety, Hospital Universitario 12 de Octubre, ³Primary Care Management, Comunidad de Madrid, Madrid, Spain

Contact E-mail Address: jose.diazta@salud.madrid.org

Introduction: There is evidence that a significant proportion of colonoscopies performed worldwide do not comply with clinical guidelines. This inadequacy on the medical prescription has important consequences on its diagnostic performance, the patient´s safety and costs. Results of educational interventions have been inconsistent in previous studies. The development of software tools, incorporated in the electronic medical record, might have a role in improving prescriptions' appropriateness.

Aims & Methods

Aims: To evaluate the effectiveness of a software application, integrated in the colonoscopy electronic request form of an university hospital and designed as prescription aid, to decrease colonoscopy prescription inadequacy.

Methods: Observational prospective study. An electronic colonoscopy request form has been designed including the algorithms and the recommendations for follow up on its most relevant indications and providing real time information on the procedures appropriateness on each clinical context. Six hundred colonoscopy prescriptions were evaluated before (PRE period) and after (POST period) software implementation. The colonoscopy was considered “appropriate” if it met the recommendations of any of the following guidelines with a six month difference or less: Spanish Gastroenterological Association Colorectal Cancer Prevention Guideline, European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis or European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE II) categories “appropriate and necessary”, “appropriate” or “uncertain”.

Results: 1084 prescriptions were included in the analysis, 519 PRE / 565 POST, (average age 59.5 +- 14.6 y.o., 49.32% females). There is a significant reduction in the inapropriateness rate after the implementation of the software: PRE 21.19% VS POST 9.20% (p < 0.001). This improvement is statistically significant in the follow-up after surgical treatment of colorectal cancer and endoscopic resection of early colorrectal neoplasia (table).

TABLE.

INAPPROPRIATENESS in PRE (n = 519) and POST (n = 565) PERIODS, disaggregated by indication. Data are shown as n(%).

Indication	PRE	POST	p
Anemia	1 (2.70)	0 (0)	0.21
Hematochezia	1 (3.23)	2 (3.03)	0.96
Constipation	1 (5.56)	2 (7.41)	0.81
Abdominal pain	2 (11.76)	3 (37.50)	0.13
Diarrhea	3 (8.11)	0 (0)	0.01*
Inflammatory bowel disease	4 (5.71)	1 (2.17)	0.36
Surveillance after endoscopic resection	59 (49.17)	26 (33.33)	0.03*
Surveillance after surgical resection of cancer	21 (35.00)	7 (15.22)	0.02*
Screening (high risk population)	6 (13.04)	5 (10.64)	0.72
FOBT +	0 (0.00)	1 (2.94)	0.48
Others	12 (18.18)	5 (6.42)	0.03*

Conclusion: The implementation of a decision-making aid software tool improves appropriateness of colonoscopy prescription.

Disclosure of Interest: None declared

P0193 IMPACT OF BOWEL PREPARATION QUALITY ON ADENOMA IDENTIFICATION DURING COLONOSCOPY AND OPTIMAL TIMING OF SURVEILLANCE

J. S. Kim¹, S. H. Kang¹, H. S. Moon¹, S. H. Kim¹, J. K. Sung¹, H. Y. Jeong¹

¹Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea

Contact E-mail Address: showsik@hanmail.net

Introduction: Present guidelines stating the surveillance interval after index colonoscopy are all based on optimal bowel preparation. However, in the case of poor bowel preparation, appropriate timing of repeat colonoscopy is not clear.

Aims & Methods: We compared adenoma detection rate and missing rate according to the status of bowel preparation in order to determine the appropriate timing of repeating colonoscopy in cases of poor bowel preparation. The medical records of patients who underwent colonoscopy in the last 5 years were retrospectively analyzed. Index colonoscopy was defined as the first colonoscopy in patients who received at least twice during the study period. Adenoma miss rate (AMR) was calculated by dividing the number of patients where at least one adenoma was detected during repeated colonoscopy by the total number of patients who received repeated colonoscopy. Bowl preparation quality was defined as optimal, fair, and poor.

Results: The overall adenoma detection rate (ADR) was 39.1% (95% confidence interval [CI], 38.0–40.1). However, the detection rate was significantly different based on bowel preparation status (optimal; 46.8%, fair; 25.6%, poor; 21.6%, P < 0.001). AMR was also significantly increased with poor bowel preparation (optimal; 27.3%, fair; 48.1%, poor; 69.6%, P < 0.001). We compared the AMR of optimal bowel preparation group with fair and poor bowel preparation groups on the basis of the repeat colonoscopy interval. When compared with the optimal bowel preparation group, AMR was significantly increased in both the poor and fair bowel preparation group for repeated colonoscopy within 2 years (poor group: OR 6.25; 95% CI, 3.76–11.83, fair group: OR 3.67; 95% CI, 2.19–6.16); however, there was no difference after 2 years.

Conclusion: Bowel preparation quality significantly affects AMR. Repeated colonoscopy should be performed within 2 years in patients who have received colonoscopy under suboptimal bowel preparation conditions.

Disclosure of Interest: None declared

P0194 ENDOSCOPIC MUCOSAL RESECTION OF COLORECTAL LESIONS LARGER THAN 2 CM: THE EXPERIENCE IN A DISTRICT HOSPITAL

J. Pinho¹, D. Martins¹, P. Sousa¹, E. Cancela¹, R. Araújo¹, A. Castanheira¹, P. Ministro¹, A. Silva¹

¹Centro Hospitalar Tondela Viseu, Viseu, Portugal

Contact E-mail Address: julianapinho18@gmail.com

Introduction: Endoscopic mucosal resection (EMR) has been shown to be useful in the removal of large lesions of the gastrointestinal tract. The aim of this study was to evaluate the experience of our hospital on the efficiency and safety of EMR in colorectal lesions, using inject and cut technique.

Aims & Methods: We did a retrospective study based on the EMR performed between June 2009 and June 2013. Resected lesions ≥20 mm in diameter were selected. The histological characteristics, complications, follow up and surgical needs were evaluated.

Results: During the study period, we performed 266 EMRs; 114 EMRs were performed in lesions ≥20 mm in diameter among 110 patients (64 men and 46 women) with an average age of 67.7 ± 11.8 years. The lesions average size was 30.9 mm, having 58% been located in the colon and 42% in the rectum. According to the Paris classification, the lesions were classified as: Is-77; IIa-33; IIb-3; IIa + IIc-1. Piecemeal resection was performed in 76% of cases. A complete endoscopic resection was achieved in 93% of the cases. Post-EMR argon plasma coagulation was applied in 18 lesions (16%). The histopathological results revealed: adenoma with high-grade dysplasia - 57; adenoma with low-grade dysplasia - 34; adenoma with focal adenocarcinoma - 13; invasive adenocarcinoma - 5; serrated adenoma - 6. Complications occurred in 4.4% of the procedures (1 intra-procedural bleeding; 2 delayed bleedings; 2 perforations). Until now, 226 follow up colonoscopies were performed in 94 patients. The average follow up time was 21.2 months, with endoscopic control ranging from 1 to 64 months post-EMR. Local recurrence occurred in 25 patients (22%), and the majority (88%) was managed with polypectomy or new EMR. Ten patients (8.8%) were referred for surgery, 50% because of histological evidence of invasive adenocarcinoma.

Conclusion: EMR is a safe and effective technique for colorectal lesions larger than 2 cm, with low risk of recurrence and complications. Local recurrences were successfully treated with endoscopic resection, avoiding the need for surgery in 88% of cases.

Disclosure of Interest: None declared

P0195 INCREASED INSULIN RESISTANCE IS AN INDEPENDENT RISK FACTOR FOR POST-ERCP PANCREATITIS

A. R. Koksal¹, S. Boga¹, H. Alkim¹, M. Bayram¹, M. Ergun¹, C. Alkim¹

¹Gastroenterology, Sisli Etfal Education and Research Hospital, Istanbul, Turkey

Contact E-mail Address: arkoksal@gmail.com

Introduction: The relationship between insulin resistance and post-ERCP pancreatitis (PEP) was not known. We aimed to determine whether increased pre-ERCP insulin resistance is associated with an increased risk of PEP or not, and to evaluate the relationship of insulin resistance with well-established risk factors of PEP.

Aims & Methods: Consecutive patients who underwent ERCP with the diagnosis of choledocolithiasis between July and December 2013 were enrolled to this prospective study. Pre-procedural insulin resistance state and other risk factors were evaluated according to PEP development.

Results: Pancreatitis developed in 16 (11.3%) of 141 ERCP procedure. HOMA-IR (3.37 ± 0.8 vs 2.38 ± 1.4, p < 0.001) levels was found statistically significantly higher in patients who developed PEP than the ones who didn’t. According to logistic regression analysis HOMA-IR ≥ 2.5 (OR:3.92), pancreatic duct cannulation (OR:4.09), procedure time (per minute OR:1.09), common bile duct diameter (per millimeter OR:0.80) and age (per year OR:1.05) were the important factors increasing PEP risk.

	PEP	Non-PEP	p value
Age	60 ± 15	58.8 ± 16.1	0.97
BMI kg/m2	29.8 ± 3	27.9 ± 4.4	0.44
ALT (U/L)	99.6 ± 83	72.9 ± 71.7	0.03
MPV (fl)	8.9 ± 0.9	9.7 ± 1.2	0.01
Platelet Count (/mm3)	237168 ± 68029	294259 ± 112605	0.05
Total Bilirubin (mg/dl)	1.5 ± 0.9	1.8 ± 1.8	0.69
HOMA IR	3.37 ± 0.8	2.38 ± 1.4	<0.001
Procedure time (min.)	33.5 ± 9	27.9 ± 7.2	0.006
CBD diameter (mm.)	10.1 ± 4	13.4 ± 4.5	0.01

Conclusion: According to our results, presence of insulin resistance is an independent risk factor for the development of PEP and increases the risk at least similar to the known risk factor of pancreatic canal cannulation.

Disclosure of Interest: None declared

P0196 COMPARATIVE STUDY ON THE SAFETY AND EFFICACY OF PROPOFOL INDUCED CONSCIOUS SEDATION DURING ERCP BETWEEN ANAESTHESIOLOGIST AND OTHER (NON - ANAESTHESIOLOGISTS) APPROPRIATELY TRAINED PHYSICIANS

A. Koutsoumourakis¹, G. Lazaraki¹, D. Tzilves¹, I. Pilpilidis¹, K. Soufleris¹, O. Abraam¹, S. Anisoglou², A. Tarpagkos¹

¹Department of Gastroenterology, ²Department of Anaesthesiology, Theagenio Cancer Hospital, Thessaloniki, Greece

Contact E-mail Address: koutsoumourakis@gmail.com

Introduction: During the last years, propofol has become the preferred short-acting sedation agent offering an alternative to the benzodiazepine midazolam anaesthetic induction agent during diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP).

Aims & Methods: The aim of this retrospective study was to compare the safety and efficacy of propofol-induced conscious sedation in patients class I (normal healthy subjects), II (subjects with mild systemic disease) and III (subjects with non-incapacitating severe systemic disease,) according to the American Society of Anaesthesiologists ASA Physical Status Classification, undergoing ERCP administered either by anaesthesiologists or other (non-anaesthesiologists) appropriately trained physicians. Data from 2012-2014 were collected retrospectively by use of the Electronic Endoscopy Report Data Base at our center. A total of 195 patients (98 men, 69.61 ± 14.05 years and 97 women, 69.21 ± 13.78 years, respectively) were divided into propofol sedation group A under the supervision of the anaesthesiologist (N=122, 62 men, 69.21 ± 13.78 years and 60 women, 69.73 ± 13.36 years, respectively) or into propofol sedation group B under the supervision of the non-anaesthesiologist appropriately trained endoscopist (N=73, 36 men 70.77 ± 13.40 years and 37 women, 68.24 ± 14.51 years, respectively). Blood pressure, pulse, and oxygen saturation were measured. Propofol was administered either by the anaesthesiologist or by the endoscopist and titrated to the patients' response during ERCP to a maximum dose of 1-2 mg per kg.

Results: There was no significant statistical differences between two groups with respect to median age (p=0.618), to sex (p= 0.639), to ASA classification (p= 0.612), to indication for ECP (p= 0.451), to serum bilirubin level (p= 0.984) and to endoscopist experience (p= 0.538). The mean required propofol during the procedure in the group A and B were 354.15 ± 210.74 mg and 217.5 ± 93.3 mg, respectively (t-difference: 7.342; p> 0.05). Furthermore, there was no statistical difference in selective cannulation of the common bile duct (86% versus 89%, p= 0.597) between the two groups. Only three patients (1/62 men and 2/60 women) developed sedation-related cardiorespiratory complications in group A and no patient in group B (p=0.14).

Conclusion: Appropriately trained endoscopist-directed administration of propofol is totally safe and effective for providing propofol sedation in patients ASA Class I, II and III during ERCP.

Disclosure of Interest: None declared

P0197 PREDICTIVE FACTORS FOR POST-ERCP PANCREATITIS: ABOUT A LARGE MONOCENTRIC STUDY

B. Bouchabou¹, A. Oukaa¹, O. Daboussi¹, N. Bibani¹, H. Elloumi¹, D. Trad¹, D. Gargouri¹, J. Kharrat¹

¹Gastroenterology, Habib Thameur Hospital, Tunis, Tunisia

Contact E-mail Address: oussama_dab@hotmail.fr

Introduction: Pancreatitis is the most common and serious complication of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). Prevention strategies targeting risk factors could be important to reduce the rate of post-ERCP pancreatitis. However, the risk factors for post-ERCP pancreatitis (PEP) are still debated.

Aims & Methods

Aim: This systematic review ananalysis was performed to determine the prevalence of PEP and to identify its risk factors.

Methods: We conducted a retrospective study in a single center by reviewing all consecutive cases in which ERCP was performed between January 2010 and January 2015. The existence of pancreatitis before the procedure was an exclusion criteria. All patients remained in the hospital for at least 24 hours after the procedure to monitor them for clinical manifestations of pancreatitis. Serum amylase and lipase levels were measured at 4 and 24 hours (the next morning) after ERCP. We evaluated 8 variables, including patient-related factors and procedure related factors that could be analyzed in detail based on information in the patients’ charts.

Results: A total of 1794 patients were included in our study.Therapeutic ERCP had been performed in all cases. 73% of cases were for common bile duct stones and in 27% of cases for biliary stent . Thirty five patients developed PEP with a prevalence of 1.95%. On univariate analysis, precut sphincterotomy (p = 0.008) and pancreatic duct cannulation (p = 0.002) were found to be significantly associated with PEP. On multivariate analysis, significant risk factors were: at least two pancreatic duct injections (p = 0.05) and age younger than 75 years (p = 0.01).

Conclusion: History of acute pancreatitis, precut sphincterotomy and pancreatic duct cannulation were all identified as independent risk factors for PEP.

Disclosure of Interest: None declared

P0198 PRECUT FISTULOTOMY: CANNULATION EFICIENCY AND RISK OF POST ERCP COMPLICATIONS IN A NOVEL TERTIARY HOSPITAL IN LIMA PERU

C. F. Gutierrez¹, V. F. Parra¹, H. Nuñez¹, J. R. Flores¹

¹Gastroenterologia, Hospital Nacional Hipolito Unanue, Lima, Peru

Contact E-mail Address: fernagut@hotmail.com

Introduction: Precut sphincterotomy (PS) has controversial data about its performance and complications that are not fully elucidated. There are different types os PS. Precut Fistulotomy (PF) is a type of PS that employs a needle knife to create an incision at the level of the intraduodenal segment of the common biliary duct avoiding papillary orifice. Recent data show low risk of PEP for this technique in expert hands.

Aims & Methods

Aims: To evaluate success and safety of Precut Fistulotomy(PF), and the risk of complications, specially post ERCP pancreatits (PEP).

Methods: Between June 2012 and November 2013 a single-center prospective cohort study with retrospective analysis on 167 consecutive patients with native papillas referred for ERCP was conducted. Patients elegible were those referred for first ERCP at hospital over 18 years old. All patients were hospitalized 48h before and at least 48h after procedure. The major Indication for ERCP were choledocolithiasis suspected (88%). We intent a selective wire guided cannulation (WGC) in all patients. After 15 minutes of unsuccessfully cannulation or 2 unintentional guidewire advance into pancreatic duct (PD) the endoscopist realize PF by protocol. Success in cannulation was defined as deep placement of a catheter into the common bile duct. A diagnosis and severity of complication was made according to Cotton´s classification. 4 endoscopists were involved in study (more than 200 ERCP each one 50 ERCP per year) but less than 5 year of experience. Complications were retrospectively evaluated.

Results: We collect 167 patients in the study time with a median age of 49.18 + 18.27. Female patients were 118 (72.39%).The main diagnosis post ERCP were: choledocolithiasis 114 (69.93%) oddities 22(13.50%) stone migration (6.13%) benign biliary stricture or bile leak 11 (6.75%) biliary malignancy (1.78%). WGC was successful in 119 patients (71.25%). Success cannulation with PF was reach in 163 patiens (97.6%). The overall incidence of PEP for PF patients was 20.5% vs 3.5% in those without PF (p = 0.001 RR 6.03). Unintentional pancreatic cannulation was the other significant factor for PEP (40.8% vs 4% p< 0.001 RR 8.40). These factors maintain its relation with PEP in de logistic regression model. There is no difference about bleeding rate between patients with PF or not (2.33% vs 2.52% p=0.59).

Conclusion: Precut Fistulotomy is a useful technique that importantly improve successful cannulation. PF does not increase bleeding risk in our cohort but in this novel center we found a slightly increased risk of PEP. Future trials must evaluate if PF could be a risk factor for PEP in centers with low-volume ERCP biliary endoscopists.

Disclosure of Interest: None declared

P0199 EFFICACY OF ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY IN PANCREATIC FISTULAS

E. Rodrigues-Pinto¹, P. Pereira¹, P. Moutinho-Ribeiro¹, A. Ribeiro¹, J. A. Sarmento¹, F. Vilas-Boas¹, G. Macedo¹

¹Gastroenterology, Centro Hospitalar São João, oPorto, Portugal

Contact E-mail Address: edu.gil.pinto@gmail.com

Introduction: Pancreatic fistulas (PF) may result from surgical resection, pancreatic trauma or chronic pancreatitis. Endoscopic retrograde cholangiopancreatography (ERCP) allows a faster resolution of PF, by performing pancreatic sphincterotomy (S) and/or placement of pancreatic stents (PS) with 5/7Fr.

Aims & Methods: Assess the role of ERCP in the treatment of PF. Cross-sectional study of patients referred for ERCP due to PF.

Results: Fifteen patients (10 males) had PF in pancreatogram, 5 in the cephalic portion, 1 in the neck, 6 in the body and 3 in the tail. Ten patients (66.7%) had undergone previous surgery, with the remaining being secondary to pancreatitis (n=3; 20%) or traumatic transection (n=2; 13.3%). Six of the operated patients had splenectomy. Median time to ERCP was 23 days. Fourteen patients (93.3%) placed PS and 8 (53.3%) performed S. Eleven patients (73.3%) resolved PF endoscopically, 24 days (8 – 401) after ERCP; 1 patient repeated ERCP, with the 3 remaining requiring surgery. Splenectomy was associated with endoscopic failure (50% vs 0%, p=0.048). PS >5cm and/or 7Fr were associated with a trend towards higher endoscopic resolution, respectively, 87.5% vs 66.7% (p=0.348) and 100% vs 72.7% (p=0.198). Time till endoscopic resolution was tend shorter when surgical fistulas (28 days vs 34 days, p=0.270), when PS with 7Fr (22 days vs 28 days, p=0.203) or >5cm (14 days vs 34 days, p=0.301).

Conclusion: ERCP with PS and S is effective in 75% of patients with PF. PS >5cm or 7Fr may be more effective. Associated splenectomy is associated with endoscopic resolution failure.

Disclosure of Interest: None declared

P0200 LIMITATIONS OF PLASTIC STENTS IN MALIGNANT BILIARY DRAINAGE OF BILIARY OBSTRUCTION CAUSED BY PANCREATIC ADENOCARCINOMA

E. Rodrigues-Pinto¹, P. Pereira¹, P. Moutinho-Ribeiro¹, A. Ribeiro¹, J. A. Sarmento¹, F. Vilas-Boas¹, J. Santos-Antunes¹, G. Macedo¹

¹Gastroenterology, Centro Hospitalar São João, oPorto, Portugal

Contact E-mail Address: edu.gil.pinto@gmail.com

Introduction: Plastic stents (PS) are cheaper, however, have lower patency than metal stents in pancreatic adenocarcinoma (PA).

Aims & Methods: Assess patency of different stents in biliary drainage of biliary obstruction condition by PA. Cross-sectional study of patients referred for endoscopic retrograde cholangiopancreatography (ERCP) for biliary drainage of biliary obstruction conditioned by PA.

Results: Seventy-nine patients underwent biliary drainage. Adjuvant therapy was performed in 49%, carried out prior to drainage in 41% of cases. PS were placed in 57% of patients, of which, 82% were 10Fr/11.5Fr and 22% were >7cm. ERCP was repeated in 29% of the patients. In patients with survival longer than 30 days, ERPC was repeated when adjuvant therapy was performed after ERCP (45% vs 7%, p=0.009, OR 10.8) and when PS were placed (49% vs 10%, p=0.001, OR 8.3). There was a tendency to repeat ERCP when stents had a smaller caliber (83% vs 43%, p=0.067). In the multivariate analysis, ERCP repetition was higher in PS (OR 9.5, p=0.002). Stents patency was 76 days (IQR: 42 – 164), being lower in PS (p=0.001) and in these, when smaller caliber (42 days vs 133 days, p=0.017) or bigger dimensions (59 days vs 133 days, p=0.024). Number of hospital admissions and ERCP repetition due to stent dysfunction was higher in PS (respectively, 49% vs 12%, p < 0.001, OR 7.2 and 42% vs 6%, p < 0.001, OR 11.6).

Conclusion: ERCP repetition is more common in PS. Patency is lower in PS, and in these, when smaller caliber or bigger dimensions.

Disclosure of Interest: None declared

P0201 IS PLASTIC BILIARY STENTING IN CHOLEDOCHOLITHIASIS A LONG TIME SAFETY PROCEDURE? A RETROSPECTIVE MULTICENTRIC STUDY

E. Quintanilla¹, A. Castillo¹, M. Delgado², J. L. Castro¹, A. Repiso³, M. L. Arias¹, M. Pérez¹, L. Rábago¹

¹Gastroenterology Department, Hospital Universitario Severo Ochoa, Leganés, Madrid, ²Gastroenterology Department, Hospital Universitario Infanta Elena, Valdemoro, Madrid, ³Gastroenterology Department, Hospital Virgen de La Salud, Toledo, Spain

Contact E-mail Address: elviramquintanilla@hotmail.com

Introduction: Plastic biliary stenting in patients with choledocholithiasis is suitable until a second ERCP or surgery. This option has demonstrated the fragmentation and dissapearence of large size bile duct stones. Also, it is a simple and safe method for high-risk surgical patients.

Aims & Methods

Objective: To study the effectiveness of plastic biliary stenting in patients with incomplete choledocholothiasis removal, as final technique or as a bridge for additional endoscopic or surgical intervention.

Materials and Methods: Retrospective and multicentric study based on a review of ERCP performed between October 2005 and January 2015.

Results: 72 ERCP were enrolled (52 patients), 26 male and 26 female (50%).

The therapeutic indications were: incomplete removal (n43, 82.69%), intradiverticular papilla (n4, 7.7%) and others (n5, 9.6%). In most cases, they had anaesthetic risk (n36, 69.23%) and the endoscopic procedure was suspended due to severe oxygen desaturation in 3 patients.

The size of plastic biliary stent usually used was 7 or 10 cm and 8,5Fr or 10Fr. In general, patients with 10Fr stent showed less complications than patients with 8,5Fr stent (38.8% vs 62.5%)

We established three groups of patients:

1. Plastic biliary stenting as definitive technique (n15, 28.8%) with an average age of 82.07 ± 12.38. 33.3% of patients delivered biliary disease (4 cholangitis, 1 biliary colic) in an average time of 15.6 months, without migration of stent. In these cases, we changed the stent in 3 patients and stone clearance with removal the stent in 2. After this, these patients were asymptomatic. Five patients died of causes not related and carried the stent during an average time of 10.6 months.

2. Plastic biliary stenting as a brigde for surgical intervention (n9, 17.3%). 33.3% of patients showed biliary disease (1 cholecystitis 6 months after initial placement, 1 pancreatitis 1 month after placement and 1 biliary colic, 18 months after). These patients underwent elective cholecystectomy. Surgical intervention was carried out in an average time of 2.75 months.

3. Patients with additional ERCP (n28, 53.8%). 22 patients (78.2%) needed 2 ERCP getting stone fragmentation and/or removal in most cases (n17, 77.2%). 6 patients (21.5%) needed more than 2 ERCP to successfully resolve the bile duct obstruction in 83.3% (n5). Only 3 patients (10.7%) required a surgical intervention for the resolution of choledocholithiasis.

Conclusion: According to these results, the effectiveness of plastic biliary stenting are directly related with placement time. Plastic stent as a final option needs to be replaced annually. As a bridge for surgical intervention, this procedure should be carried out before 3 months. In patients with additional ERCP, it is an effective measure. However further studies are required to confirm this data.

Disclosure of Interest: None declared

P0202 POST-ERCP PANCREATITIS (PEP) – DOES ROUTINE USE OF RECTAL INDOMETHACIN AFFECT OUTCOMES? A HIGH-VOLUME SINGLE-CENTRE EXPERIENCE FROM THE UK

F. Abid¹, M. T. Huggett¹, J. M. Hutchinson², S. M. Everett¹, M. H. Davies², R. E. England³

¹Gastroenterology, ²Hepatology, ³Radiology, St James University Hospital, Leeds, Leeds, United Kingdom

Contact E-mail Address: faisal.abid@nhs.net

Introduction: Post-ERCP pancreatitis (PEP) is a common but potentially life-threatening complication of ERCP with an incidence of up to 10% in unselected patients in large international series¹. A number of prospective trials have shown that administration of rectal indomethacin is beneficial in reducing the incidence of PEP in high-risk patients². We aimed to compare the rate and severity of PEP in an unselected group during the pre and post-indomethacin era at our hospital, which has one of the largest ERCP practices in the UK.

Aims & Methods: A retrospective analysis of a prospectively-collected ERCP database in all adult patients undergoing ERCP from January 2011 to December 2014. In 2011 no rectal indomethacin was given, whilst in 2014 all patients recieved it. In 2012-13 only high-risk patients recieved indomethacin. Therefore, the unselected patient cohorts from 2011 (pre group) and 2014 (post group) were compared. PEP was diagnosed and categorised into mild, moderate and severe according to Cotton’s 1991 consensus guidelines³.

Results: 1432 patients were included. Of 717 patients in the pre group, 27 (3.7%) developed pancreatitis, 11 (1.5%) mild, 10 (1.4%) moderate and 6 (0.8%) severe with 4 deaths. Of 715 patients in the post group, 21 (2.9%) developed PEP; 15 (2%) mild, 4 (0.6%) moderate and 2 (0.3%) severe with 1 death. There was no difference in the overall incidence of pancreatitis between the post and pre groups [OR 0.77; p=0.38], but the combined incidence of moderate and severe PEP was significantly lower in the post group [OR 0.37; p=0.03]. There was no difference in haemorrhage rates in post 7 (0.9%) vs pre group 5 (0.7%)[OR 1.45; p=0.56].

Conclusion: We observed that in our cohort of patients the unselected use of rectal indomethacin did not significantly reduce the incidence of PEP, however there was a significant reduction in moderate to severe PEP. This study therefore suggests a beneficial effect of the routine use of rectal indomethacin in unselected patients, consistent with current European Society of Gastrointestinal Endoscopy (ESGE) recommendations.

Disclosure of Interest: None declared

P0203 COMPARISON OF CONVENTIONAL DUODENOSCOPE AND SINGLE-BALLOON ENTEROSCOPE TO PERFORM ERCP IN PATIENTS WITH BILLROTH II GASTRECTOMY

G. Mbatshi¹, T. Aouattah¹, R. Yeung¹, E. Macken², B. Roth², H. U. De Schepper², H. Piessevaux¹, P. H. Deprez¹, T. G. Moreels¹

¹Gastroenterology & Hepatology, Cliniques Universitaires Saint-Luc, Brussels, ²Gastroenterology & Hepatology, Antwerp University Hospital, Antwerp, Belgium

Contact E-mail Address: tmoreels@gmail.com

Introduction: Billroth II partial gastrectomy precludes conventional endoscopic retrograde cholangiopancreatography (ERCP) because of altered anatomy. It renders ERCP more difficult because of the intubation of the afferent limb and the orientation of the intact papilla.

Aims & Methods: Comparison of ERCP procedures performed with the conventional duodenoscope and the single-balloon enteroscope (SBE) in Billroth II patients in 2 university endoscopy units. 34 Billroth II patients underwent 64 ERCP procedures between 2006 and 2014. Technical aspects, therapeutic success and complications were recorded.

Results: Male/female ratio was 20/14 (59/41%) with a mean age of 72 ± 1 (48-91) years. The initial choice of endoscope type was at the endoscopist’s discretion. 29 (45%) ERCPs were started using a duodenoscope of whom 25 (86%) were successful and 3 were completed using SBE. 21 (33%) ERCPs were started using SBE of whom 16 (76%) were successful and 2 were completed using a pediatric colonoscope. 5 (8%) ERCPs were started using a pediatric colonoscope of whom 4 were completed with a duodenoscope and 2 with the SBE. In total 9 (14%) procedures needed a change of endoscope type in order to complete the procedure. Overall therapeutic success rate using a duodenoscope was 87% vs 81% using SBE (P > 0.05; Chis-square), whereas success rate using a pediatric colonoscope was only 43% (P < 0.05; Chi-square). Complication rate using a duodenoscope was 7% (pancreatitis; embolism) vs 14% (pancreatitis; biliary leak) using SBE (P > 0.05; Chi-square), without mortality. The use of a duodenoscope allowed complete sphincterotomy and both plastic and metallic stent placement, whereas the use of SBE often needed to combine sphincterotomy with additional sphincteroplasty (8-15 mm) and only 7 Fr plastic stent placement was possible due to the 2.8 mm working channel diameter. However, SBE allowed easy access to the papilla in the afferent limb and sphincteroplasty often allowed direct cholangioscopy using SBE. Indications were bile duct stones (55%), chronic pancreatitis (26%), cholangitis (16%), livertransplantation (3%).

Conclusion: Therapeutic ERCP success rate is high in patients with Billroth II gastrectomy using either a conventional duodenoscope or the SBE, with an acceptable and comparable complication rate. The choice of endoscope may depend on the endoscopist’s experience, postoperative anatomy (gastrojejunostomy and length of afferent limb) and therapeutic indication (metallic stent placement and direct cholangioscopy).

Disclosure of Interest: None declared

P0204 BALLOON CATHETER VERSUS BASKET CATHETER FOR ENDOSCOPIC BILE DUCT STONE EXTRACTION: A MULTICENTRE, PROSPECTIVE RANDOMISED CONTROLLED TRIAL

H. Ishiwatari¹, H. Hisai², K. Yane³, M. Onodera⁴, T. Hayashi¹, K. Eto⁵, S. Haba⁶, T. Okuda⁷, H. Ihara⁸, T. Kukitsu⁹, R. Matsumoto¹⁰, K. Kawakubo¹¹, K. Kitaoka¹², M. Ono¹, H. Kawakami¹¹, A. Katanuma³, T. Sonoda¹³

¹Department of Medical Oncology and Hematology, Sapporo Medical University, Sapporo, ²Japanese Red Cross Date General Hospital, Date, ³Teine-Keijinkai Hospital, Sapporo, ⁴Abashiri-Kosei General Hospital, Abashiri, ⁵Tomakomai City Hospital, Tomakomai, ⁶NTT East Japan Sapporo Hospital, Sapporo, ⁷Oji General Hospital, Tomakomai, ⁸KKR Sapporo Medical Center Tonan Hospital, Sapporo, ⁹Rumoi City Hospital, Rumoi, ¹⁰Obihiro-Kosei General hospital, Obihiro, ¹¹Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, ¹²Otaru Ekisaikai Hospital, Otaru, ¹³Department of Public Health, Sapporo Medical University, Sapporo, Japan

Contact E-mail Address: ishihiro481019@gmail.com

Introduction: Endoscopic bile duct stone (BDS) removal using the basket or balloon catheter is a well-established treatment. However, the choice of extraction devices depends on the operator’s preference because there has been no study comparing outcomes with the two catheters.

Aims & Methods: We conducted a non-inferiority trial to investigate the performance of individual catheter for stone extraction. Patients with a BDS diameter ≤10 mm and common bile duct diameter ≤15 mm were enrolled in this study. The participants were randomly assigned to groups that were treated with the basket or the balloon catheter at 12 hospitals from October 2013 through September 2014. After stone extraction with the assigned catheter was completed, balloon occlusion cholangiography was performed in both groups to confirm the clearance of the duct. Primary endpoint was the rate of complete clearance of the duct by the assigned catheter. Secondary endpoints were the rate and time of complete clearance in one endoscopic session.

Results: We initially enrolled 172 consecutive patients, but 14 patients were excluded after randomisation. The total number of patients available for analysis was 158. The rates of complete clearance by the assigned catheter were 92.3% (72/78) in the balloon group and 80.0% (64/80) in the basket group. The difference of the rates between the two groups was -12.3%, indicating failure of non-inferiority of the basket catheter (non-inferiority limit 10%; p=0.17 for non-inferiority). However, the results revealed superiority of the balloon over the basket catheter (p=0.037). There were no significant differences in secondary endpoints.

Conclusion: The balloon catheter is recommended for a first-line device of endoscopic BDS removal. This study was registered on the UMIN Clinical Trial Registry (UMIN000011887).

Disclosure of Interest: None declared

P0205 A NOVEL MODIFIED APPROACH TO SINGLE-BALLOON ENTEROSCOPY FOR ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY IN PATIENTS WITH ALTERED GASTROINTESTINAL ANATOMY

H. Tamaki¹, T. Noda¹, S. Arasawa¹, M. Izuta¹, A. Kubo¹, C. Ogawa¹, T. Matsunaka¹, M. Shibatoge¹

¹Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Kagawa, Japan

Contact E-mail Address: h-tama@gc4.so-net.ne.jp

Introduction: Although increasing evidence of the usefulness of single-balloon enteroscopy (SBE) for endoscopic retrograde cholangiopancreatography (ERCP) has been reported in postoperative patients with altered gastrointestinal anatomy, no short-type SBE has been made available in the market. Thereafter, the technical limitations or parameters of SBE (working length, 200 cm; working channel diameter, 2.8 mm; SIF-Q260, Olympus Medical Systems Corp., Tokyo, Japan) necessitate the use of prototype endoscopic instrumentation or the replacement of SIF-Q260 with another endoscope through the overtube.

Aims & Methods: We evaluated the efficacy of a novel SBE approach by using PCF-PQ260L (with passive bending and high-force transmission; working length, 168 cm; working channel diameter, 2.8 mm; Olympus Medical Systems Corp.) in patients with an altered gastrointestinal anatomy, without the use of special or prototype instrumentation or an enteroscope replacement. Between February 2012 and March 2015, 38 modified SBE-assisted ERCP procedures were performed in 24 postoperative patients (15 men and 9 women; mean age, 64.7 years [range, 25–93 years]) with altered gastrointestinal anatomy (Roux-en-Y hepaticojejunostomy, 16 procedures in 6 patients; Roux-en-Y gastrectomy, 9 procedures in 7 patients; Billroth-II gastrectomy, 7 procedures in 5 patients; pancreatoduodenectomy, 4 procedures in 4 patients; and gastrojejunostomy, 2 procedures in 2 patients). In all of the cases, a side hole was made 110 cm from the distal end of the overtube. ERCP was performed by inserting a PCF-PQ260L through the side hole of the overtube and then into the gastrointestinal tract. We retrospectively evaluated the success rate of reaching the blind end, the mean time required to reach the blind end, the diagnostic success rate, the therapeutic success rate, the mean procedure time, and the complications.

Results: Endoscopic therapeutic procedures were performed as follows: plastic biliary stent (ERBD) insertion, 15 times in 10 patients, including endoscopic sphincterotomy (EST) performed 4 times; balloon dilatation for stenosis of hepaticojejunal anastomosis, 5 times in 2 patients; choledocholithiasis extraction, 5 times in 5 patients, including EST performed 4 times; removal of ERBD, 3 times in 2 patients; endoscopic nasobiliary drainage, once; and removal of debris from the bile duct, once. In the remaining 4 patients, brush cytology of the pancreatic duct and cholangiography were performed. The success rate of reaching the blind end was 97.4% (37/38 patients). The mean time required to reach the blind end was 28.3 ± 24.0 min. The diagnostic success rate was 92.1% (35/38 patients). The mean procedure time was 59.4 ± 39.5 min. The success rate of the overall modified SBE-assisted ERC was 89.5% (34/38 patients). The complication rate was 23.7% (hyperamylasemia in 9 patients).

Conclusion: Diagnostic and therapeutic ERCP using our novel approach of modifying SBE without the use of a special or prototype instrumentation, or an enteroscope replacement is sufficiently safe and effective. It may potentially serve as an alternative to the SBE-assisted ERCP with SIF-Q260.

Disclosure of Interest: None declared

P0206 DICLOPHENAC POTASSIUM VERSUS CEPHTAZIDIME FOR REDUCTION OF POST ERCP PANCREATITIS IN AVERAGE RISK PATIENTS-RANDOMISED DOUBLE BLIND CONTROLLED TRIAL

G. Hauser¹, I. Blazevic², N. Salkic³, G. Poropat¹, V. Giljaca¹, Z. Bulic¹, D. Stimac¹

¹Department of Internal Med., Division of Gastroent, ²Department of Emergency Medicine, Clinical Hospital Centre, Rijeka, Croatia, Rijeka, Croatia, ³Department of Gastroenterology and Hepatology, University Clinical Centre Tuzla, Tuzla, Bosnia and Herzegovina

Contact E-mail Address: goran.hauser@medri.uniri.hr

Introduction: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common major complication of ERCP. Its incidence has substantial variations ranging from 5.1% to more than 25% of all ERCP procedures. In some cases pancreatitis is followed by severe course with pancreatic necrosis and multiorgan failure. Diclophenac sodium together with indometacine is currently standard treatment in prevention of PEP while ceftazidime is possible alternative treatment for patients with contraindication for nonsteroidal anti-inflammatory drugs (NSAID).

Aims & Methods: The primary aim of this study was to determine whether prophylactic, parenteraly administered ceftazidime reduces the frequency of PEP compared to rectally applied diclofenac sodium. All eligible patients who underwent ERCP in tertiary care center during a 20-month period (June 2013 to February 2015) were enrolled in this study. Estimating the prevalence of PEP of 10% and reduction of incidence of 50% (α=0.02, beta =0.95) calculated total sample size was 248. In a double-blinded randomized controlled trial, patients received a suppository containing a 100 mg of diclofenac sodium rectally and placebo intravenously (group A) or 1g of ceftazidime intravenously and placebo rectally (group B) immediately before the procedure. PEP was diagnosed according to the standardized criteria (Cotton criteria). The study was registered at Clinical Trial.gov (NCT01784445)

Results: We included 272 patients, mean age of 71.9 years (SD ± 12.2), female 128 (47%). There were 129 (47.4%) patients in the diclofenac sodium group and 143 (52.6%) in the ceftazidime group. The occurrence of post-ERCP pancreatitis (PEP) in complete sample was 11.8% (32/272). There was no statistical difference in occurrence of PEP between diclofenac and ceftazidime group (RR=1.72; 95%CI=0.86-3.43, P=0.17). PEP incidence in females was similar in booth groups 7(11.7%) in diclophenac sodium and 11(16.2%) in ceftazidime group (RR=0.7212; 95%CI 0.29 to 1.74, P=0.46).

Conclusion: There are no statistically significant difference in incidence of PEP among patients who received ceftazidime or diclophenac potassium. Ceftazidime may be used as alternative treatment for prevening PEP in patients with contraincidations for NSAID.

Disclosure of Interest: None declared

P0207 FULLY COVERED SELF-EXPANDABLE METAL STENTS TO DILATE PANCREATIC DUCT STRICTURES DUE TO CHRONIC PANCRERATITIS: A PILOT STUDY

A. Tringali¹, P. Familiari², F. Barbaro¹, I. *Boskoški¹, G. Gigante¹, V. Perri¹, G. Costamagna¹

¹Digestive Endoscopy Unit, Catholic University, Rome, Italy, ²Digestive Endoscopy Unit, Catholic University, Rome, -

Contact E-mail Address: andrea.tringali@rm.unicatt.it

Introduction: Main pancreatic duct (MPD) strictures due to chronic pancreatitis (CP) may be treated endoscopically by insertion of single or multiple plastic stents. MPD stricture resolution after plastic stents removal occurs in near 60% of the cases.

Aims & Methods: We evaluate the use of removable fully covered, self expandable metal stents (FC-SEMS) to dilate MPD strictures secondary to CP. Patients with CP and symptomatic MPD strictures in the head of the pancreas that persisted >3 months after placement of a single plastic stent, were enrolled into a prospective single arm trial. The protocol was approved from the Ethic Committee of our University. A Nitinol FC-SEMS (Bumpy stent, Taewoong) was inserted and removed after 6 months. FC-SEMS diameter (6 or 8 mm) and length (3, 4, 5 cm) were chosen according to stricture anatomy and MPD diameter above the stricture. Stricture resolution was defined as a satisfactory pancreatico-duodenal contrast medium outflow and absence of pain during continuous flushing with saline (1000ml/day) for 24 hours through a 6 french naso-pancreatic drain. Primary objective was FC-SEMS removability. Secondary objectives were MPD stricture resolution rate and complications. Follow-up was planned every 6 months during a 2 year. Pancreatic pain episodes and recurrence of pancreatitis were recorded.

Results: Between Dec 2012 and Oct 2014, 15 patients (10M, mean age 60 y) were enrolled. Pancreatic calcifications were present in 6(40%) and ESWL was performed in 4. Four patients (27%) had a history of alcohol abuse. In 10 cases the FC-SEMS was inserted through the major papilla (7 had a previous biliary sphincterotomy, 2 had pancreatic sphincterotomy alone, 1 had choledochoduodenostomy), while 5 patients (3 pancreas divisum, 2 dominant dorsal duct) received the FC-SEMS through the minor papilla. One patient developed cholangitis after 24 hours due to occlusion of the biliary sphincterotomy from the FC-SEMS; cholangitis resolved after insertion of a plastic biliary stent. During stenting period 13 patients (87%) were asymptomatic while 2 had recurrent pancreatitis after 4 and 5 months; the FC-SEMS had migrated and the persistent MPD stricture was treated with a plastic stent. FC-SEMS completely migrated in 7 patients and could be removed endoscopically in the remaining 8 cases. Four patients (27%) developed a tight stricture induced by FC-SEMS at the level of its proximal end; in one case the stricture was overcome only after EUS-guided pancreatic rendez-vous. Follow-up is ongoing. Results are summarized in the table.

	N	%	Follow-up,mean months (range)
Patients	15	-	-
FC-SEMS removability	8/8	100	-
Complete FC-SEMS distal migration	7/15	47	-
FC-SEMS proximal migration	1/8	12
MPD stricture resolution	10/15	67	-
SEMS “induced” MPD stricture	4/15	27	-
Asymptomatic	8/14*	57	12 (5-18)

*One patient excluded from follow-up (pancreatic cancer diagnosed 6 months after stent removal).

Conclusion: FC-SEMS removability from the MPD in chronic pancreatitis was feasible in all cases. After 1-year follow-up 57% of the patients were asymptomatic; this figure is similar to those obtained with plastic stents. Occurrence of FC-SEMS induced pancreatic strictures is a major issue and deserves further assessment. According to our experience the use of FC-SEMS in the MPD needs careful evaluation in the setting of clinical trials.

Disclosure of Interest: A. Tringali Lecture fee(s): Boston Scientific, P. Familiari: None declared, F. Barbaro: None declared, I. Boskoški Consultancy: Cook Endoscopy, G. Gigante: None declared, V. Perri: None declared, G. Costamagna Consultancy: Cook endoscopy, Olympus, Boston Scientific

P0208 FEASIBILITY AND PRELIMINARY SAFETY STUDY OF A NEW NITINOL “SOFT” FULLY COVERED SELF-EXPANDING PANCREATIC METAL STENT IN CHRONIC PANCREATITIS

J. Deviere¹, M. Fernandez¹, J. Peetermans², A. Lemmers¹

¹Ulb Erasme, Brussels, Belgium, ²BSCI, Marborough, United States

Contact E-mail Address: jacques.deviere@erasme.ulb.ac.be

Introduction: Multiple plastic stents are used for calibrating distal stricture in severe chronic pancreatitis. A single metal stent which does not require exchanges would be useful in this setting.

Aims & Methods: Document feasibility and preliminary safety in ongoing pancreatic endotherapy in patients (pts) with painful chronic pancreatitis (CP) of Cremer Type IV using a new Nitinol “Soft” fully covered (6 mm diameter) self-expanding metal stent (Panc SEMS) (Pancreatic WallFlex, Boston Scientific Corporation, Marlborough, USA). Ten (10) patients enrolled. Intended Panc SEMS indwell 3 mo in 5 pts and 6 mo in 5 pts. Follow-up to 24 mo ongoing. Interim results reported on ITT basis.

Results: 10 pts (mean age 48, 60% male). CP etiology 60% alcoholic, 10% hereditary, 30% unknown. Calcific CP in 70% of pts. All pts had prior plastic stent placement(s) during a mean of 3 yrs (range 4 mo to 6 yrs). No pts had a prior Panc SEMS. At time of interim analysis, all pts were stent free with mean time on study 262 d (range 218-326 d) and mean stent-free period of 95 d (range 22-193 d). In total 14 stents were placed, with 2 pts having immediate removal and replacement of the initial stent due to deployment in unsatisfactory position and 2 pts needing a second stent placement after premature complete distal migration. Stent migration without symptoms, thought to be a reflection of adequate calibration of the benign stricture, occurred in 6 stent placements, not requiring restenting. Clinically meaningful complete distal migration (CDM) with symptoms occurred in 21% (3/14) stent placements. There were no proximal stent migrations. Endoscopic stent removal was performed per-protocol easily in one pt after 3 mo indwell and in 2 pts after 6 mo indwell without stent removal-related adverse events (AEs). To date 80% (8/10) pts remain stent free and follow-up is ongoing. One pt had premature CDM followed by placement of plastic stents. One pt had no pain relief after SEMS placement and had subsequent pancreatic diversion surgery which did not provide pain relief either. Mean Izbicki pain scores were 59 (range 15-86) at baseline, 42 (range 0-88) at time of SEMS removal or observation of complete distal migration, and 44 range (0-90) at last visit. AEs occurred in 50% (5/10) of pts, with 7 AEs (2 pain associated with premature CDM, and at time of SEMS placement 3 transient pain, 1 bacterial infection, and 1 mild acute pancreatitis). No SEMS needed to be removed due to intolerable pain after SEMS placement. There were no stent-induced ductal changes.

Conclusion: Feasibility of FC SEMS implantation and removal in pts undergoing pancreatic endotherapy was confirmed. Preliminary safety was acceptable with only mild adverse events, represented mainly by anticipated pain after implantation. SEMS removability was achieved without adverse events in all patients, either per protocol or by spontaneous complete distal migration. No stent induced ductal changes were observed at the time of removal. Further study to assess effectiveness of pancreatic endotherapy

Disclosure of Interest: None declared

P0209 ERCP QUALITY EVALUATION THROUGH SELF-ASSESSMENT AND OUTCOMES

J. García-Cano¹, M. A. Godoy-López², L. Taberna-Arana³

¹Department of Digestive Diseases, ²Department of Radiology, Hospital Virgen de la Luz, ³Family Practice, Health District of Cuenca, Cuenca, Spain

Contact E-mail Address: jgcl7@live.com

Introduction: ERCP is one the most difficult gastrointestinal endoscopic procedures, therefore monitoring and enhancing the quality of this interventionn is of paramount importance.

Aims & Methods: All ERCPs performed in our center from January 2009 to September 2014 were prospectively included in a specific ERCP database. Procedures were analyzed retrospectively with a modification of the Rotterdam Assessment Form for ERCP (RAF-E) [1] that has proven to provide insight into the quality of individual ERCP performance and can be used to assess and set standards for quality control in ERCP. Only naïve papillae were considered as it is well known that after biliary sphincterotomy, cannulation and ERCP completion is usually easier. MRCP was routinely performed before ERCP.

Results: A total number of 363 ERCPs with naïve papilla were performed in this period of time by a single endoscopist. Results according to the retrospective appraisal using the modified RAF-E are shown in the table.

Abstract number: P0209

Biliary condition	n	CBD deep cannulation	Biliary sphincterotomy	Balloon dilation	Stent insertion	Successful biliary drainage	mortality
1.Papillary stenosis, migrated CBD stones	30	28 (93.33%)	28 (100%)	0	10/10 (100%)	28 (93.33%)	0
2.Stones < 10mm	90	87 (96.66%)	79/79 (100%)	EPBD up to 10 mm 28/28 (100%)	15/15 (100%)	87 (96.66%)	0
3.Malignant extrahepatic strictures	83	80 (96.38%)	72/72 (100%)	0	78/80 (97.5%)	73 (88%)	2/83 (2.4%)
4.Benign extrahepatic strictures	37	35 (94.59%)	35/35 (100%)	0	35/35 (100%)	35 (94.59%)	0
5.Biliary leaks	12	11 (91.66%)	11/11 (100%)	0	11/11 (100%)	11 (91.66%)	0
6.Stones > 10mm	51	50 (98%)	50/50 (100%)	Large EPBD27/31 (87%)	19/19 (100%)	49 (98%)	0
7.Hilar strictures	32	29 (90%)	29/29 (100%)	10/10 (100%)	28/29 (96%)	27 (84%)	1/32 (3%)
8.Billroth II anatomy	28	26 (93%)	0	16/16 (100%)	12/12 (100%)	26 (93%)	0
TOTAL	363	346 (95.3%)	254 (100%)	81(95%)	222 (98%)	336 (94%)	3/363 (0.8%)

CBD= Common Bile Duct. EPBD= endoscopic papillary balloon dilation. For small CBD stone extraction it was employed up to 10 mm. For larger CBD stones, 12-18 mm balloon diameter was used. In Billroth II balloon dilation and stent insertion were always performed after inserting a plastic stent in the Main Pancreatic Duct without previous sphincterotomy.

According to degrees of difficulty based on Schutz’s classification [2], ERCP indications 1-5 correspond to level 1, 6-7 to level 2 and 8 to level 3. Diagnostic cholangiography or pancreatic procedures were never performed. For CBD cannulation a sphincterotom loaded with a guidewire was used.

Conclusion: Self-assessment is a valuable method to gain insight in ERCP performance. Outcomes can be compared with those obtained in centers of excellence to promote improvement. It appears that CBD deep cannulation can be considered as a surrogate for successful biliary drainage because it was accomplished in 97% of occasions after cannulation in the eight biliary scenarios reported in this study.

Disclosure of Interest: None declared

P0210 ESTIMATED INCIDENCE OF MULTI-DRUG RESISTANT ORGANISMS AMONG DUODENOSCOPE TRANSMITTED INFECTION: RESULTS FROM A NATIONAL SPANISH SURVEY

J. García-Cano¹, M. Pérez-Miranda², F. González-Huix³, L. López-Rosés⁴, J. J. Vila-Costas⁵, E. Brullet-Benedí⁶, on behalf of On behalf of the Biliopancreatic group of the Sociedad Española de Endoscopia Digestiva (SEED)

¹Department of Digestive Diseases, Hospital Virgen de la Luz, Cuenca, ²Department of Digestive Diseases, Hospital Rio Hortega, Valladolid, ³Department of Digestive Diseases, Clinica Girona, Girona, ⁴Department of Digestive Diseases, Lucus Augusti Hospital, Lugo, ⁵Department of Digestive Diseases, Complejo Hospitalario de Navarra, Pamplona, ⁶Department of Digestive Diseases, Corporació Sanitària Parc Taulí, Sabadell, Spain

Contact E-mail Address: jgcl7@live.com

Introduction: Transmission of Multi-Drug Resistent Organisms (MDROs) has recently been linked to duodenoscopes. The epidemiology of this potentially serious problem is poorly understood. Variability across Units in endoscope cleaning and disinfection methods has received limited attention to date.

Aims & Methods: To survey the incidence of duodenoscope-transmitted infection overall and of MDRO in particular in Spain. Members of the Sociedad Española de Endosocopia Digestiva (SEED) registered at institutions offering ERCP were sent a questionnaire about disinfection standards and instances of duodenoscope transmitted infection in their Units. Self-reported recall data were pooled for analysis.

Results: Seventy one hospitals from across Spain participated in the study. The total estimated procedure volume covered by respondents was 70,000 ERCPs over a 5-yr period. 3/71 (4.2%) centres performed manual cleaning of the duodenoscopes. No infection transmission was reported from any of these hospitals. 68/71 (95.8%) units had automatic washing methods for cleaning. Thirteen infectious outbreaks linked to duodenoscopes were reported from 13 different centres. Only four of these outbreaks were related to MDRO. Three MDRO outbreaks involved multiple patients (Klebsiella Carbapenemase in two centers and Escherichia Coli producing extended-spectrum beta-lactamases in another) and a single patient in another (MDR Klebsiella). Microbiological genotyping revealed a common MDRO in patients referred from different hospitals to a single referral Unit. Clinical course ranged from fever to severe sepsis requiring ICU admission. MDRO was judged a potentially contributing factor in two postoperative deaths. A single patient was infected in the remaining 9 outbreaks. Isolated microorganisms were: Klebsiella species (4), Escherichia Coli (1), Enteroccocus (1), Pseudomonas (1), Serratia (1), Candida (1). No patient died. Routine microbiologic assessment of disinfections practices had only been performed in 2/13 centers with outbreaks. Corrective measures were implemented in all cases with MDRO

Conclusion: Duodenoscope transmitted infection was observed in 13 out of 71 centers (18.3%), with MDRO identified in 30% of outbreaks, typically involving multiple cases. Despite the limitations of this survey, it provides further evidence of duodenoscope-transmitted MDRO as an emerging problem. There is a need to address critical cleaning steps in the chain-of-transmission, pending future improvements in scope design.

Disclosure of Interest: None declared

P0211 SMALL PAPILLA OF VATER AS A RISK FACTOR FOR POST-ERCP PANCREATITIS

J. García-Cano¹, M. A. Godoy-López², L. Taberna-Arana³

¹Department of Digestive Diseases, ²Department of Radiiology, Hospital Virgen de la Luz, ³Family Practice, District Health of Cuenca, Cuenca, Spain

Contact E-mail Address: jgcl7@live.com

Introduction: The pathogenesis of Post-ERCP pancreatitis (PEP) is multifactorial; mechanical injury, hydrostatic injury, chemical and thermal injury, have been postulated as factors for PEP development. Uchino et al. [1] suggested that a small papilla can also be considered as a risk factor for PEP. A small papilla makes the pancreatic orifice susceptible to trauma, which ultimately leads to pancreatitis.

Aims & Methods: A small papilla of Vater was defined as having less than 3 mm in size and/or the absence of a caudal fold (plica papillae). These criteria were applied retrospectively to a series of ERCP with naïve papilla with detailed reports. Common Bile Duct (CBD) drainage was the purpose of all ERCPs. CBD cannulation was always attempted with a sphincterotome loaded with a guidewire

Results: Main results are shown in the table.

Table.

Pancreatitis rate according to papilla of Vater size

	n	PostERCP pancreatitis rate	Mortality
Normal papilla	94	8 (8.5%)	0
Small papilla	18	4 (22%)	1/18 (5.5)

Both groups were matched in terms of age, gender, ERCP indication, easy or difficult cannulation, precut use and stent insertion without biliary sphincterotomy.

Both pancreatitis and mortality rate showed a p < 0.05 between normal and small size papillas. The patient who died was an 80-yr old woman who had a very easy procedure. A 10 french biliary stent was inserted without sphincterotomy for CBD drainage. Biliary sphincterotomy to remove CBD stones was not attempted because of a small papilla of Vater with no clear landmarks for cutting. The patient suffered from a severe pancreatitis and died 72 hours later.

Conclusion: In this small series study, it appears that a small size papilla is a risk factor for PEP. Pancreatitis severity appears to be also greater when biliary sphincterotomy is not performed [2]. Further studies are warranted to confirm these results.

Disclosure of Interest: None declared

P0212 PARTIALLY COVERED VERSUS UNCOVERED SELF-EXPANDABLE NITINOL STENTS WITH ANTI-MIGRATION PROPERTIES FOR THE PALLIATION OF MALIGNANT DISTAL BILIARY OBSTRUCTION: A RANDOMIZED CONTROLLED TRIAL

J. H. Kim¹, M. J. Yang¹, B. M. Yoo¹, J. C. Hwang¹

¹Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea

Contact E-mail Address: jinhkim@ajou.ac.kr

Introduction: Covered self-expandable metal stents (SEMSs) are increasingly used as alternatives to uncovered SEMSs for the palliation of inoperable malignant distal biliary obstruction to counteract tumor ingrowth.

Aims & Methods: The aims of this study were to compare the outcomes of partially covered and uncovered SEMSs with identical mesh structures and anti-migration properties, such as low axial force and flared ends. One hundred and three patients who were diagnosed with inoperable malignant distal biliary obstruction between January 2006 and August 2013 at a single tertiary center were randomly assigned to either the partially covered (n = 51) or uncovered (n = 52) SEMS group.

Results: There were no significant differences in the cumulative stent patency, overall patient survival, stent dysfunction-free survival, and overall adverse events, including pancreatitis and cholecystitis, between the two groups. Compared to the uncovered group, stent migration (5.9% vs. 0%, P = 0.118) and tumor overgrowth (7.8% vs. 1.9%, P = 0.205) were non-significantly more frequent in the partially covered group, whereas tumor ingrowth showed a significantly higher incidence in the uncovered group (5.9% vs. 19.2%, P = 0.041). Stent migration in the partially covered group occurred only in patients with short stenosis of the utmost distal bile duct (two in ampullary cancer, one in bile duct cancer), and did not occur in any patients with pancreatic cancer.

Conclusion: For the palliation of malignant distal biliary obstruction, endoscopic placement of partially covered SEMSs with anti-migration designs and identical mesh structures to uncovered SEMSs failed to prolong cumulative stent patency or reduce stent migration.

Disclosure of Interest: None declared

P0213 PROSPECTIVE, COMPARATIVE TRIAL EVALUATING FREE HAND INSERTION OF A SCOPE INTO THE BILE DUCT WITH MULTIBENDING VERSUS CONVENTIONAL ULTRASLIM ENDOSCOPE FOR DIRECT PERORAL CHOLANGIOSCOPY

J. H. Moon¹, Y. N. Lee¹, H. J. Choi¹, M. H. Choi¹, T. H. Lee¹, S.-W. Cha¹, Y. D. Cho¹, S.-H. Park¹

¹Digestive Disease Center and Research Institute, Department of Internal Medicine, SoonChunHyang University School of Medicine, Bucheon and Seoul, Republic of Korea

Contact E-mail Address: jhmoon@schmc.ac.kr

Introduction: Direct peroral cholangioscopy (DPOC) using an ultraslim endoscope has been increasingly applied for diagnosis and treatment of diverse biliary diseases. However, the usefulness of DPOC is limited by low, inconsistent success rates. The success rate can be increased by assistance of several accessories, but it’s technically demanded and cumbersome. In addition, maintenance of desired scope position during interventional procedure is difficult.

Aims & Methods: The aim of this study was to evaluate the success rate of free-hand direct insertion into the bile duct using a newly developed multibending ultraslim endoscope as for a dedicated cholangioscope for DPOC. A total of 52 patients with biliary disease were prospectively enrolled. Each patient was performed two trials of DPOCs using a multibending ultraslim endoscope (Olympus Co., Tokyo, Japan) after a conventional ultraslim scope (GIF-XP290N, Olympus) without assistance of accessories. If a DPOC using multibending ultraslim endoscope without accessory failed, an intraductal balloon-guided DPOC was performed. The success was defined as successful advancement of the endoscope into the bifurcation or the obstructed segment of the biliary tree within 15 minute without accessory.

Results: The success rate of a DPOC using multibending endoscope without accessory was significantly higher than a DPOC using a conventional endoscope (90.4% vs. 28.8%; p<0.001). The 5 patients failed in DPOC using multibending endoscope without accessory were all success with an intraductal balloon-guided DPOC using multibending endoscope. The success of interventional procedures was achieved with 36 of 37 (97.8%) trials including 11 intraductal biopsies, 9 intraductal lithotripsy. Adverse event was observed in one patient of mild hemobilia.

Conclusion: A high success rate of free hand direct insertion of a scope into the bile duct was achieved with newly developed multibending ultraslim endoscope with experienced endoscopist. DPOC without assistance of accessories can be possible with further development.

Disclosure of Interest: None declared

P0214 SAFETY OF ENDOSCOPIC PANCREATIC SPHINCTEROTOMY IN EXPERT HANDS

K. R. Makhejani¹, M. M.-U.-. Haq¹, R. H. Awan¹, A. L. Memon¹

¹Gastroenterology, Liaquat National Hospital, Karachi, Pakistan

Contact E-mail Address: drkrm2003@gmail.com

Introduction: Endoscopic biliary sphincterotomy has been commonly used for biliary and pancreatic duct diseases, in cases of difficult biliary duct canulation, various methods like precut and endoscopic pancreatic sphincterotomy (EPDS) has been used. Various studies have reported variable rate of complications after doing EPDS. Thus, we examined the indications and rate of complications in one of the largest center for endoscopic retrograde cholangiopancreatograph.

Aims & Methods: Among patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) between January 2012 and December 2014, 40 patients who underwent endoscopic pancreatic duct sphincterotomy (EPDS) were included in this retrospective study. We examined the indications, complications and safety of procedure.

Results: Out of 40 patients 52.5% were female and 47.5% were male. Diagnostic and therapeutic indications for ERCP were recurrent pancreatitis (10 cases), pancreatic pseudocyst (2 cases), and mass at porta hepatis (1 cases) pancreatic duct leakage (2 cases), cbd stone (3 cases), biliary stricture with obstructive jaundice (12 cases). The success rate of EPDS was 100% (40/40). Acute complications of EPDS included three cases (7.5%) of mild pancreatitis and no other complication was noted.

Conclusion: EPDS showed a very low incidence of complications and a high rate of treatment success; thus, EPDS is a relatively safe procedure when performed by an expert endoscopist

Disclosure of Interest: None declared

P0215 AN OBJECTIVE APPROACH TO QUANTIFY TISSUE OBTAINED FROM ENDOSCOPIC ULTRASOUND GUIDED FINE NEEDLE BIOPSY (EUS-FNB): A POTENTIALLY IMPORTANT TOOL FOR FUTURE EUS-GUIDED BIOPSY TRIALS

A. V. Phan¹, A. Ruszkiewicz², N. Q. Nguyen¹

¹Medicine, University of Adelaide, ²Pathology, Royal Adelaide Hospital, Adelaide, Australia

Contact E-mail Address: quoc.nguyen@health.sa.gov.au

Introduction: Endoscopic ultrasound (EUS) guided tissue acquisition, with a fine needle, allows cytologic and/or histologic diagnosis of lesions within or adjacent to the gastrointestinal tract (GIT). Given most needles used so far are fine needle aspiration (FNA), the “traditional” primary outcome has been a cytological diagnosis. The recent development of core-like needles aims to increase the amount of tissue acquired for “histological” assessment. Apart from the conventional “tissue diagnosis”, there has been no method or criteria to objectively quantify the tissue obtained from different EUS FNA needles. This may explain for the indifferences in trials that compared FNA versus FNB needles.

Aims & Methods: The aim was to evaluate an objective method to quantify the tissue acquired by EUS-guided biopsy using core needles.

Methods: Tissue acquired from biopsy of pancreatic mass by EUS-FNA technique was prospectively obtained from 18 subjects with suspected pancreatic malignancy. In each case, all material from two needle passes of either 22G or 25G Procore needle were flushed into a 5ml-bottle of formalin for direct histological processing, which involved extracting the material from the bottle (without spinning) for routine paraffin processing and generating slides as if the specimen was a “histological specimen". One of every 3 slides will be reviewed for presence of diagnostic material by a dedicated cyto-pathologist. In order to objectively quantify the tissue acquired from the needle, the slides will be scanned using the NanoZoomer (Hamamatsu Phototonic, Japan) and high definition images will be stored electronically. Using the associated software (NDP.view2, Phototonic, Japan), the characteristics of the diagnostic tissue will be further quantified by objectively assessing the length, width, presence of tissue-core (defined as tissue showing preserved architectural integrity, in which the length of the core is at least twice of the nominal inner diameter of the used needle), and the total surface area of diagnostic tissue.

Results: This approach was used to examine EUS guided biopsied specimens from 18 subjects with pancreatic mass, using 22-G Procore needle (n=10) and 25-G Procore (n=8). The final pathological diagnoses were achieved in all cases, with 16 invasive adenocarcinomas and 2 neuroendocrine tumour with Ki67 determination. When compared the tissue characteristics between the 22G and 25G Procore needle, both needles were able to acquired tissue-cores, but the cores were larger (376 ± 9.72 vs.262 ± 16.01 μm; P <0.0001) and longer (1.93 ± 0.22 mm vs. 0.96 ± 0.18 mm; P < 0.02) with the 22G than the 25G Procore needle. Most importantly, the 22G Procore needle able to acquire more diagnostic material than the 25G needle, as quantified by the total surface area of diagnostic tissue (1.67 ± 0.51 mm² vs. 0.52 ± 0.14 mm²; P=0.05).

Conclusion: The characteristic and amount of tissue acquired from EUS guided biopsy can be objectively quantified by using the direct histological processing and NanoZoomer assessment. This method has great potential for research use, especially in the evaluation the outcome of different types of needles in practice of EUS guided biopsy.

Disclosure of Interest: None declared

P0216 SINGLE SESSION EUS-RENDEZVOUS ERCP VERSUS PERCUTANEOUS BILIARY DRAINAGE IN PATIENTS WITH FAILED COMMON BILE DUCT ACCESS AFTER ERCP

A. Y. B. Teoh¹, T. Iwashita², V. Dhir³, T. Mukai², A. Maydeo³, F. K. L. Chan⁴, J. Y. W. Lau¹

¹Surgery, Chinese University of Hong Kong, Hong Kong, Hong Kong, ²Gastroenterology, Gifu University Hospital, Gifu, Japan, ³Gastroenterology, Baldota Institute of Digestive Sciences, Mumbai, India, ⁴Gastroenterology, Chinese University of Hong Kong, Hong Kong, Hong Kong

Contact E-mail Address: anthonyteoh@surgery.cuhk.edu.hk

Introduction: Common bile duct access (CBD) may fail in less than 5% of the patients undergoing ERCP. Traditionally, these patients will require percutaneous biliary drainage. However, the advent of EUS-biliary drainage provides another endoscopic means of achieving CBD access at the same session of failed ERCP. However, how single session EUS-rendezvous ERCP (ERV) compares to percutaneous biliary drainage is not known.

Aims & Methods: This was a multicentre study (3 Asian hospitals, 2 university affiliated) of all patients that underwent single session EUS-rendezvous ERCP after failed CBD access by ERCP, performed between January 2012 and October 2014. The outcomes of these patients were retrospectively compared to those that received percutaneous-rendezvous ERCP or antegrade stenting (PTBD) prior to the introduction of the EUS technique. These procedures were believed to be comparable as the goal of the procedures was to achieve transpapillary CBD access for subsequent interventions. The main outcome parameters included the success rate in gaining CBD access, adverse event rates, the number of sessions of interventions required in each patient to obtain CBD access and luminal drainage.

Results: A total of 128 patients were included (ERV:PTBD = 64:64). There were no differenced in background demographics (table 1). A high success rate in obtaining CBD access (92.2% vs 100%, P = 0.056) and achieving luminal drainage (93.8% vs 85.9%, P = 0.241) was observed in both groups. This was possible in a single session in all patients within the ERV group. Whilst, the median (range) number of sessions required to obtain CBD access in the PTBD arm was 2 (1-2), P < 0.0001. Similarly, significantly more interventions were required in the PTBD group to achieve transluminal drainage (3 [2-9] sessions, P = 0.032). The adverse events rates were comparable between the 2 groups (17.2% vs 23.4%, P = 0.510). The most common adverse events were cholangitis (6.2%) in the ERV arm and tube dislodgement (9.4%) in the PTBD group.

Conclusion: Single-session EUS-rendezvous ERCP may replace PTBD as the procedure of choice in patients with failed ERCP. The procedure allows same session CBD access and luminal drainage with avoidance tube related adverse events.

Disclosure of Interest: None declared

P0217 ADVERSE EVENTS OF ENDOSCOPIC ULTRASOUND-GUIDED FINE NEEDLE ASPIRATION OF PANCREATIC CYSTIC LESIONS USING THE LEXICON PROPOSED IN AN ASGE WORKSHOP: A PROSPECTIVE STUDY

A. J. Rodriguez-D'Jesus¹, G. Fernández-Esparrach¹, C. Marra-Lopez², A. Orive-Calzada², O. Sendino¹, I. Araujo¹, C. Rodríguez de Miguel¹, H. Cordova¹, B. González-Suárez¹, A. Ginès¹

¹Endoscopy Unit, Gastroenterology Department, Hospital Clínic. Barcelona, Spain, ²Endoscopy Unit, Gastroenterology Department, Hospital Universitario Araba, Vitoria-Gasteiz, Spain

Contact E-mail Address: magines@clinic.ub.es

Introduction: There is concern about the safety of endoscopic ultrasound-guided fine needle aspiration of pancreatic cystic lesions. The aim of this study is to assess the incidence of adverse events of the technique in this setting using the lexicon recommended by ASGE.

Aims & Methods: Patients with pancreatic cystic lesions undergoing an endoscopic ultrasound-guided fine needle aspiration were prospectively included. A 22 gauge-needle was used in all patients. The procedure was performed under conscious sedation. A complete cystic fluid evacuation with a single needle pass was attempted in all cases. Patients received ciprofloxacin during the procedure and 3 days after. Adverse events were defined and graded following the lexicon recommended by ASGE. Patients were followed at 48 hours, one week and day 30 after the procedure. Potential predictive factors for adverse events were analyzed.

Results: A total of 132 patients were included and 7 adverse events (5.3%) were recorded: fever (n=3, 2.3%); acute pancreatitis (n=3, 2.3%) and cholangitis (n=1, 0.75%). All adverse events had an early presentation (before 48 hours post-procedure) and resolved with medical therapy. All the episodes of pancreatitis were observed in patients with chronic pancreatitis or with a previous episode of acute pancreatitis (p < 0.05). We did not find any other variable related with the development of adverse events.

Conclusion: Endoscopic ultrasound-guided fine needle aspiration of pancreatic cystic lesions has a rate of adverse events slightly higher than that of solid masses, but small enough to consider this procedure a secure way to guide management of these patients.

Disclosure of Interest: None declared

P0218 THE ROLE OF ENDOSCOPIC ULTRASOUND IN THE EVALUATION AND MANAGEMENT OF GASTROINTESTINAL STROMAL TUMORS

A. G. Antunes¹, M. Eusébio¹, A. Vaz¹, P. Queirós², T. Gago¹, A. Vieira², H. Tavares², B. Peixe¹, H. Guerreiro¹

¹Gastroenterology Department, Centro Hospitalar do Algarve, Faro, ²Gastroenterology Department, Centro Hospitalar do Algarve, Portimão, Portugal

Contact E-mail Address: sergiogiao@hotmail.com

Introduction: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal gastrointestinal tumors (MTs), corresponding in most post-mortem studies, to less than 3% of gastrointestinal malignancies. Although its relatively indolent course, all GISTs are considered as potentially malignant, and so, its essential to stratify the tumors according to the relative risk of progression.

Aims & Methods: (1) Descriptive analysis of the experience of our center in the diagnosis and monitoring of MTs with the main focus on GISTs; (2) to assess the role of endoscopic ultrasonography in the identification of high risk-stigmata, and the correlation between endosonographic features and histological predictors of malignancy.

Retrospective analysis of all new cases of MTs, in the period between 2010 and 2014. We recorded demographic, clinical, pathological and radiological data. Risk stratification was performed according to the TNM classification and the Miettinen criteria. Endosonography high-risk stigmata was defined as presence of heterogeneous echopattern, cystic spaces, irregular extra-luminal margin and large tumor (≥ 4 cm). Histological malignancy was defined as > 5 mitoses on a total area of 5mm²

Results: We identified 54 patients with mesenchymal tumors, 37 with immunohistochemistry confirmation of being a GIST. There was equal distribution between genders, with a mean age of 68 years. At diagnosis, 5 patients had a synchronous tumor (3 colorectal cancer). The mean size was 5.7 cm, being the spindle cell (81%) the most common subtype. Stomach was the most frequent localization (70%), followed by the small bowel. Concerning clinical presentation, in 50% it was an incidentaloma, gastrointestinal bleeding happened in 20% and in 10%, the diagnosis was established during the management of acute abdomen.

According to TNM classification, 83% were classified as localized disease and 24% as having high-risk of progression.

Endoscopic ultrasound was performed in 25 patients. At the first endosonography examination, 8 presented endosonographic high-risk stigmata, and were refer to surgery. In all cases, their histological analysis revealed a low mitotic index (≤ 5 mitoses on a total area of 5mm²). During the ecoendoscopic follow-up, none of the patients in the low-risk group, developed high-risk features or metastatic disease.

The mean follow-up was 24 months and the median overall survival at 2 years was 81% (localized disease: 82%; advanced disease: 63%).

Conclusion: Endoscopic ultrasound was a good method for following lesions with less potential for malignancy, avoiding the morbidities associated with an aggressive strategy. The presence of high-risk features in endoscopic ultrasound, did not correlate with the presence of histological malignancy (increased mitotic index). We identified a high prevalence of synchronous tumors.

Our data outlines the need of new prospective studies to create and validate new ecoendoscopic features for predicting histological malignancy.

Disclosure of Interest: None declared

P0219 CLINICAL IMPACT OF EUS ELASTOGRAPHY USING MEAN STRAIN HISTOGRAM VALUE: A SINGLE-CENTER EXPERIENCE

C. De Cassan¹, E. Bories¹, C. Pesenti¹, F. Caillol¹, J. P. Ratone¹, S. Godat¹, M. Giovannini¹

¹Institut Paoli Calmettes, Marseille, France

Contact E-mail Address: chiaradecassan@gmail.com

Introduction: Endoscopic ultrasound (EUS) elastography is a recent ultrasound method used for the real-time visualization and evaluation of tissue elasticity. Qualitative and quantitative methods have been used, in particular in evaluation of pancreatic diseases and malignant lymph nodes, with interesting results regarding the accuracy and the differential diagnosis between malignant and benign masses. No consensus has been reached with regard to the superiority of different quantitative methods, but strain ratio and strain histogram (SH) remain the most used. SH corresponds to a graphical representation of the color distribution in a region of interest (ROI), and mean SH (mSH) value is a SH-derived quantitative measure of the global hardness in the evaluated ROI.

Aims & Methods: The aim of the present study was to describe the different elastographic patterns of solid pancreatic masses and malignant lymph nodes using the mSH value. This is a prospective, observational, monocentric study. One experienced EUS examiner performed the endoscopic procedure and elastographic measures. SH was calculated automatically by machine integrated software in a ROI manually selected by the operator. Four parameters were calculated using the histogram to quantify the elasticity of the pancreas: the mSH, the standard deviation of the histogram, the kurtosis and the skewness. Three different measures were performed by the same operator and the mean value of the previous described values was evaluated. After the elastographic measure a FNA was performed when a lesion was observed. We used the histology obtained by FNA or surgical specimens or the global assessment of cytology and imaging as reference standard for the diagnosis, except in case of normal examinations.

Results: A total of 42 patients were included (23 F/19M): 8 normals, 22 pancreatic adenocarcinoma, 4 neuroendocrine tumors (NET), 6 malignant lymph nodes and 2 benign lymph nodes. Compared with normal patients, we found a statistically significant difference in mSH value in both patients with pancreatic adenocarcinoma (111.13 vs. 29.9, p < 0.05) and malignant lymph nodes (111.13 vs. 63.52, p < 0.05), but not in NET lesions (111.3 vs 72.9, p=0.07). A statistically significant difference was found in mSH between pancreatic adenocarcinoma and NET (29.9 vs. 72.9, p < 0.05), suggesting that mSH value could help in differential diagnosis between malignant pancreatic masses. Similarly, malignant and benign lymph nodes presented a statistically significant difference in mSH (63.52 vs 4.9, p < 0.05).

Conclusion: Mean strain histogram value seems an interesting quantitative tool to differentiate between different malignant pancreatic masses and between benign and malignant lymph nodes. A larger number of patients is needed to confirm our data.

Disclosure of Interest: None declared

P0220 DIFFERENTIAL DIAGNOSTIC EFFICACY OF ENDOSCOPIC ULTRASOUND ELASTOGRAPHY FOR CHRONIC PANCREATITIS AND PANCREATIC CANCER

E. J. Kim¹, S. Y. Kim¹, Y. S. Kim¹, J. H. Cho¹

¹Department of Gastroenterology, Gachon University, Gil Medical Center, Incheon, Republic of Korea

Contact E-mail Address: imetkim@gilhospital.com

Introduction: Endoscopic ultrasound (EUS) elastography represents a new imaging procedure that allows quantification of tissue stiffness, with a high degree of accuracy for the differential diagnosis of pancreatic disease.

Aims & Methods: The aim of this study was to evaluate the efficiency of quantitative EUS elastography for the differentiation of chronic pancreatitis (CP) and pancreatic cancer (PC). Between August 2014 and April 2015, 54 patients with PC, 39 patients with CP who underwent EUS were prospectively enrolled. EUS elastography was performed using linear Pentax EUS and Hitachi HI VISION Preirus. The quotient B/A (strain ratio; SR) is considered as the measure of the elastographic evaluation. Area A is representative of the pancreatic lesion strain. Area B refers to a soft peripancreatic tissue strain. The SR results were measured at the head and body, respectively.

Results: A total of 93 patients (mean age 60.2 years, 58 male) were included. The mean SR was 8.96 ± 6.05 for CP, 22.04 ± 13.57 for PC. The SR was different significantly in two groups respectively (CP vs. PC; p < 0.001). The area under the curve (AUC) of EUS elastography for diagnosing CP was 0.811 (95% confidence interval (CI) 0.746-0.858), the sensitivity and specificity was 71.8% and 80.2% (cut off SR of 5.81). The AUC of EUS elastography for PC was 0.983 (95% CI 0.971-0.995), the sensitivity and specificity was 94.4% and 97.4% (cut off SR of 9.15).

Conclusion: In our study, we provided the reference range of SR value of normal pancreas, CP, and PC respectively as well as good parameters of the AUC analysis. Also, EUS elastography is a promising useful method for differentiating CP and PC. Further prospective and multicenter research in this method is needed.

Disclosure of Interest: None declared

P0221 A DOUBLE APPROACH FOR ULTRASOUND-GUIDED TISSUE ACQUISITION OF PANCREATIC SOLID TUMORS IN THE ERA OF TARGET THERAPY: IS CYTOLOGY SUITABLE FOR MOLECULAR PROFILING ?

G. Delconte¹, M. Milione², C. Bezzio³, E. Meroni⁴, C. Riva², M. Bonora², G. Pelosi², V. Mazzaferro¹, E. Masci¹

¹Endoscopy Unit, Dept of Surgery, ²Dept of Pathology, IRCCS National Cancer Institute, ³Gastroenterology Unit, AO Luigi Sacco, Milan, Italy, ⁴EOC, Mendrisio, Switzerland

Contact E-mail Address: Gabriele.Delconte@istitutotumori.mi.it

Introduction: Endoscopic Ultrasound-Guided Fine Needle Aspiration (EUS-FNA) is the procedure of choice to differentiate pancreatic tumors. EUS-FNA has a good diagnostic yield particularly when procedure is performed with on-site pathologist. However, cytology alone may be not sufficient to perform immunohistochemical studies and therefore to individualized the therapy.

Aims & Methods: We evaluated the diagnostic yield of EUS-FNA on pancreatic masses using both cytological and histological approach. To do that, we retrospectively identified 122 consecutive patients (67 males, mean age 64 ± 13.7 years) who underwent EUS-FNA for solid pancreatic masses from August 2012 to January 2015. In forty-five subjects synchronous or metachronous malignancies other than pancreatic cancer were present at the time of endoscopic procedure. In most cases (115/129, 89.1%) a 22 G standard needle was used with a mean number of passes of 2.1. Obtained material was recovered in cytolit by flushing the needle with saline. There was no pathologist present in the endoscopy room. Fragments of tissue, when present, were embedded in paraffin and processed for mini-histology, whereas residual material was cytospinned and processed for cytology. Whenever collected material was adequate for that, molecular profiling was studied mainly using immunohistochemical staining.

Results: A total of 129 procedures were performed and the material collected was judged adequate for diagnosis in 112 cases. In 5 subjects with no evidence of cancer on FNA, diagnosis was supported by negative follow-up in 4 cases and by definitive histology in 1 resected lesion. A metastatic pancreatic lesion was detected in 10 out of 107 patients. Resective surgery was performed in 32 patients and initial diagnosis was confirmed in all of them but one in whom an acinar cell carcinoma resulted a mixed type tumor (endocrine and acinar). In 7 cases the procedure was repeated two times and in all of them definitive diagnosis was obtained at the second exam (overall diagnostic accuracy: 112/122, 91.8%). Cytology was judged adequate for diagnosis in 74 out of 112 cases, whereas mini-histology in 102 out of 112 cases. Adequate material for immunostaining was obtained in 84 (9 cytological and 75 mini-histological, p < 0.001) samples. In 49 patients molecular profiling was considered to be essential for a definitive diagnosis: 32 patients with other malignancies, 11 primary neuroendocrine tumors, 2 pseudopapillary solid tumors, 1 adenosquamous carcinoma, 2 acinar cell carcinoma and in one case of mixed-type carcinoma.

Conclusion: Trying to collect material for both cytology and mini-histology helps to increase the diagnostic yield of EUS-FNA, especially when on-site pathologist is not available. In our experience immunostaining is feasible in a consistent number of FNA specimens. Mini-histology is more suitable than cytology for tissue profiling and the former should be preferred when a firm diagnosis is required to target the therapy.

Disclosure of Interest: None declared

P0222 A NOVEL PIG MODEL OF BILE AND PANCREATIC DUCT DILATATION FOR EUS TRAINING

H. Shiomi¹, M. Sugimoto¹, Y. Shiomi¹, M. Takenaka¹, A. Masuda¹, Y. Arisaka¹, Y. Okabe¹, T. Azuma¹

¹Kobe University, Kobe, Japan

Contact E-mail Address: hshiomi@med.kobe-u.ac.jp

Introduction: It is known that obtaining skills of endoscopic ultrasonography is difficult, especially in the field of pancreatic and biliary disease. However, there are few animal models suitable for training in diagnostic and interventional EUS of the pancreaticobiliary field. It is not ethically acceptable that endoscopists perform practical training in patients in order to learn EUS procedure. EUS training model could help alleviate these problems.

Aims & Methods: The purpose is to develop the pig model for the training of diagnostic and interventional EUS. Abdominal operation was performed on a pig (n=8) under endotracheal general anesthesia. The external catheters were introduced into orifice of bile and pancreatic duct. The EUS model of both biliary dilatation and pancreatic duct dilatation was established. We evaluated feasibility of the model of the pancreaticobiliary disease for EUS imaging and intervention.

Results: In all pig models, EUS image showed the dilation of bile duct and pancreatic duct at 3 days after surgical procedure. Moreover, using this model, the puncture for the biliary duct and the pancreatic duct were performed under EUS and fluoroscopic guidance (n=8 success rate 100%). After puncture, a displacement of the duct diameter could be adjusted by control amount of injecting water to external catheters. Ducts were able to be dilated, and diameter of CBD and MPD were able to be controlled 10mm and 6mm respectively. In this way, our pig model was available more than ten times for puncture of these ducts. It is possible for 10 beginner endoscopists to confirm the bile and pancreatic duct, and then to perform the puncture for the bile and pancreatic duct.

Conclusion: We developed successfully the innovative model which has variable-sized ducts and repeatability of interventional EUS procedure in pancreaticobiliary field. The unconventional novel model will be very valuable for EUS training, and will surely contribute to development of interventional EUS-guided technology.

Disclosure of Interest: None declared

P0223 DIAGNOSTIC ACCURACY OF 22/25-GAUZE CORE NEEDLE IN ENDOSCOPIC ULTRASOUND-GUIDED SAMPLING OF SOLID PANCREATIC LESIONS: SYSTEMATIC REVIEW AND META-ANALYSIS

H.-C. Oh¹, H. Kang², J. H. Do¹

¹Gastroenterology, ²Anesthesiology, Chung-Ang University College of Medicine, Seoul, Republic of Korea

Contact E-mail Address: ohcgi@cau.ac.kr

Introduction: It is uncertain if novel core needle increases the diagnostic accuracy by obtaining sufficient amount of tissue. The aim of this study was to use systematic review and meta-analysis to define the diagnostic accuracy of EUS-guided core needle aspiration.

Aims & Methods: Studies were identified by searching medical databases for reports published between 1994 and 2015, using a reproducible search strategy comprised of relevant terms. Studies using 22/25G core needles, irrespective of comparison with standard fine needles, that used surgical histology or at least 6 months clinical follow-up. Pooled sensitivity, specificity, diagnostic odds ratio (DOR) and summary receiver operating characteristic (SROC) curves for the diagnosis of pancreatic malignancy were used to estimate the overall diagnostic efficiency.

Results: Eleven studies involving 929 subjects met the defined inclusion criteria. Of the 929 patients, 583 were in the core group and 346 were in the standard needle (both needles were used in 242 patients). The pooled sensitivity, specificity and diagnostic odds ratio (DOR) of the core needle were 0.88 (95%CI 0.85–0.91), 0.99 (95%CI 0.96–1) and 167.68 (64.53-435.77) respectively. The pooled sensitivity, specificity and diagnostic odds ratio (DOR) of the standard needle were 0.84 (95%CI 0.78–0.88), 1 (95%CI 0.97–1) and 129.77 (34.00-495.35) respectively. The core and standard needles were comparable in the sensitivity and specificity. In addition, the area under the curve (AUC) of core needle and standard needle in the diagnosis of pancreatic malignancy were 0.9748 and 0.9555, respectively. There were no significant differences in accuracy (RR 0.98, 95% CI 0.92, 1.04) and technical failure (RR 5.07, 95%CI 0.68-37.64). There was lower procurement of histologic core in core needle (RR 0.81, 95% CI 0.72-0.92).

Conclusion: The core and standard needles were comparable in terms of diagnostic accuracy, technical performance and safety profile. However, there was lower procurement of histologic core in the core needle group.

Disclosure of Interest: None declared

P0224 ENDOSCOPIC ULTRASOUND-GUIDED CUTTING BIOPSY FROM UPPER GASTROINTESTINAL SUBEPITHELIAL LESION USING FORWARD-VIEWING ECHOENDOSCOPE

I. Matsuzaki¹, R. Miyahara¹, Y. Hirooka², K. Funasaka², T. Yamamura², E. Ohno¹, M. Nakamura¹, H. Kawashima¹, O. Watanabe¹, H. Goto¹

¹Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, ²Endoscopy, Nagoya University Hospital, Nagoya, Japan

Contact E-mail Address: imatsu@med.nagoya-u.ac.jp

Introduction: Endoscopic ultrasound (EUS)-guided fine needle aspiration has become an accurate technique for obtaining tissue acquisition from upper gastrointestinal (GI) subepithelial lesions. However, the diagnostic yields for small lesions were relatively low. To increase the diagnostic yield, we developed EUS-guided cutting biopsy (EUS-CB) using a forward-viewing echoendoscope.

Aims & Methods: We evaluated the feasibility of EUS-CB for tissue acquisition from upper GI subepithelial lesions. This study was a prospective case series and approved by the institutional review board of the Nagoya University. Between January 2015 and April 2015, ten patients with upper gastrointestinal subepithelial lesions underwent EUS-CB by using a hot biopsy forceps. After mucosal cuts, several specimens were taken within the lesion using this forceps under real-time EUS visualization. Finally, the incision site was closed using hemoclips. The following points were assessed; (1) diagnostic yield, (2) number of samples, (3) procedure time, and (4) adverse events.

Results: Ten patients (median lesion size 16mm, range 15-44 mm) were enrolled. The overall rate of histological diagnosis of EUS-CB was 100% (10/10). The median number of samples within tumor was 4.5. The procedure times for EUS-CB and complete closure were 28.5 and 4.5 minutes. Adverse events did not occur.

Conclusion: This newly developed EUS-CB is feasible and allowed forceps biopsy from upper GI subepithelial lesions under EUS visualization.

Disclosure of Interest: None declared

P0225 EUS-GUIDED BILIARY DRAINAGE VERSUS PERCUTANEOUS TRANSHEPATIC BILIARY DRAINAGE AFTER FAILED ERCP IN MALIGNANT BILIARY OBSTRUCTION

N. Alcaide¹, L. Fernández Salazar¹, I. Peñas², M. A. Udaondo³, B. Velayos¹, C. de la Serna², L. del Olmo¹, J. Trueba³, J. M. González Hernández¹, M. Pérez-Miranda²

¹Gastroenterology, Hospital Clínico Universitario, ²Gastroenterology, Hospital Río Hortega, ³Radiology, Hospital Clínico Universitario, Valladolid, Spain

Contact E-mail Address: noelialcaide@hotmail.com

Introduction: Percutaneous transhepatic biliary drainage (PTBD) is the method of choice for the palliative relief of malignant biliary obstruction in cases where ERCP is not feasible. EUS-guided biliary drainage (EUSBD) is purported to be an alternative to PTBD in this setting. However, evidence to back this claim is still limited.

Aims & Methods

Aim: To compare safety and efficacy of EUSBD and PTBD.

Methods: Records from 40 consecutive patients with unresectable malignant biliary obstruction undergoing PTBD after failed ERCP over a 5-year period at one tertiary hospital and from 40 age and sex matched controls undergoing EUSBD for the same indication at another tertiary center in the same city were reviewed. Baseline bilirubin values, days from admission until drainage, number of sessions required, technical success rate (drain/stent placement), internal biliary drainage rate, type of stent, clinical success (80% decrease in serum bilirubin values from baseline), adverse events, procedure-related deaths, stent dysfunction, need for reinterventions, hospital stay, stent patency and overall survival were compared between the two groups. Chi-squared and Fisher’s test were used where appropriate.

Results: EUSBD: age, mean (range)= 68.12 (40-92) years; 60% male. Pancreatic cancer, 40%; Metastasis, 22.5%; Cholangiocarcinoma, 22.5%; Other, 15%. Hilar biliary obstruction in 37.5%. PTBD: age, mean (range)=72.6 (50-93); 55% male. Pancreatic cancer, 30%; Cholangiocarcinoma, 32.5%; Metastasis, 15%. Hilar biliary obstruction in 32.5%. No statistically significant differences in baseline features, including serum bilirubin, days from admission to drainage were noted between the two groups. Regarding treatment outcomes, rates of technical success, type of stent, clinical success, adverse events, stent dysfunction, stent patency, reinterventions, hospital stay, overall survival and procedure-related deaths were no different between the two groups (Table). The rate of internal biliary drainage was significantly higher in EUSBD (39 versus 32, p=0.029) and the number of sessions to obtain it was significantly lower (1.32 in EUSBD versus 2.2 in PTBD; p < 0.001).

	DBUSE	CTPH	p
Baseline Bilirubin (mg/dL)	10.65	13.64	0.077
Time from Admission to Drainage (days)	8.95	9.28	0.816
Treatment sessions (n)	1.35	2.2	0.000
Technical Success (n)	39	40	1.000
Internal biliary drainage (n)	39	32	0.029
Metal Stent (n)	32	32	0.610
Clinical Success (n)	27	25	0.750
Adverse Events (n)	6	10	0.586
Procedure-realted deaths (n)	1	2	0.215
Stent dysfunction (n)	10	7	0.586
Reinterventions (n)	22	11	0.738
Hospital Stay (days)	11.63	9.53	0.397
Stent patency (days)	89.45	111.83	0.477
Survival (days)	212	149	0.265

Conclusion: The safety and efficacy of EUSBD is comparable to that of PTBD in patients with unresectable malignant biliary obstruction and failed ERCP. The number of treatment sessions is lower with EUSBD, and the rate of internal biliary drainage higher than that of PTBD.

Disclosure of Interest: None declared

P0226 FACTORS PREDICTIVE OF CLINICAL OUTCOME FOLLOWING BILIARY DRAINAGE IN PATIENTS WITH UNRESECTABLE MALIGNANT BILIARY OBSTRUCTION AND FAILED ERCP

N. Alcaide¹, L. Fernández Salazar¹, M. A. Udaondo², I. Peñas³, B. Velayos¹, C. de la Serna³, L. del Olmo¹, J. Trueba², J. M. González Hernández¹, M. Pérez-Miranda³

¹Gastroenterology, ²Radiology, Hospital Clinico Universitario, ³Gastroenterology, Hospital Rio Hortega, Valladolid, Spain

Contact E-mail Address: noelialcaide@hotmail.com

Introduction: Unresectable malignant biliary obstruction (MBO) carries a poor prognosis. Biliary stent insertion achieves adequate palliation. Predictive factors of clinical success, procedural complications and long-term survival require further elucidation, specifically in the setting of novel procedural approaches to drainage.

Aims & Methods

Aims: To identify predictive factors of clinical outcome after technically successful biliary drainage following either percutaneous transhepatic (PTBD) or endoscopic ultrasound-guided (EUSBD) access in patients with unresectable MBO and failed ERCP.

Methods: Baseline features and clinical course of 80 patients with unresectable MBO drained by PTBD or EUSBD at two tertiary centers were retrospectively analyzed. Binary uni- and multivariate logistic regression analysis was carried out for the following dependent variables: technical success, clinical success, complications, in-hospital death, stent dysfunction, 3 and 6-month survival. Uni- and multivariate Cox proportional hazard model was performed. Independent variables analyzed were: age, sex, tumor etiology, level of obstruction, baseline bilirubin, reason for failed ERCP, days from onset of jaundice to drainage, days from failed ERCP to drainage, number of attempts, stent type, rate of internal biliary drainage, postprocedure chemotherapy. P < 0.05 was considered significant.

Results: Demographics: 57.5% male; mean (SD) age, 72.8 (13.9) years; 76.2% primary MBO vs 23.8% metastatic; 35% hilar vs 65% distal MBO. Mean survival was 161 days. Failed access to the papilla as a reason for failed ERCP was an independent predictive factor of decreased postprocedure complication risk (OR 0.178, IC 95% 0.045-0.700, p=0.014). Time from failed ERCP to final drainage procedure was an independente predictive factor of increased in-hospital death risk (OR 1.121, IC 95% 1.005-1.250, p=0.040). Hilar location was an independent predictive factor of decreased 3 and 6-month survival (OR 0.155, IC 95% 0.029-0.819, p=0.028, and OR 0.155, IC95% 0.029-0.821, p=0.028). Reintervention because of sent dysfunction was a predictor for increased 6-month survival (OR 5.839, IC 95% 1.296-26.312, p=0.022). Hilar location and reintervention for stent dysfunction were independent predictors of mortality over time (HR 1.969, IC 95% 1.037-3.737, p=0.038 y HR 0.476, IC 95% 0.254-0.890, p=0.020). PTBD versus EUSBD were not predictors for any of the dependent variables at uni- or multivariate analysis.

Conclusion: Hilar location, reason for failed ERCP, days between failed ERCP and final drainage procedure, and reintervention caused by stent dysfuncion are predictors of clinical outcome in the subset of patients with MBO and failed ERCP. These data warrant confirmation, as they are potentially relevant to improve current practice patterns.

Disclosure of Interest: None declared

P0227 THE DIAGNOSTIC YIELD OF ENDOSCOPIC ULTRASONOGRAPHY IN PATIENTS WITH SUSPECTED CHOLEDOCHOLITHIASIS

I. Hritz¹², J. Basha², R. Kalapala², M. Ramchandani², R. Gupta², N. Reddy², S. Lakhtakia²

¹Department of Gastroenterology, Bács-Kiskun County University Teaching Hospital, Kecskemet, Hungary, ²Asian Institute of Gastroenterology, Hyderabad, India

Contact E-mail Address: istvan.hritz@gmail.com

Introduction: Choledocholithiasis is the most common cause of biliary obstruction, which occurs in 10-20% of patients with cholelithiasis. Management of suspected choledocholithiasis requires confirmation of stones in the common bile duct (CBD). The diagnosis is based on clinical signs and symptoms, laboratory- and imaging examination findings. Likelihood of CBD stones can be prognosticated by the presence of various clinical predictors, however the sensitivity and specificity of these factors is moderate. Endoscopic ultrasonography (EUS) has been shown to be a non-invasive precise test for the detection of CBD stones.

Aims & Methods: Our aim was to assess the diagnostic yield of EUS in patients with suspected choledocholithiasis in a high-volume center during the period of one-month. Prospective study of patients with cholelithiasis and clinical symptoms or abnormal liver function tests who underwent transabdominal ultrasonography (USG) that could not detect CBD stones (except in one case) were categorized and divided into an intermediate- and high likelihood groups according to the clinical predictors (i.e. serum bilirubin, age, CBD diameter) defined by the American Society of Gastrointestinal Endoscopy (ASGE) guidelines and referred for radial EUS.

Results: Total of 26 patients, 14 females and 12 males (average age of 40.8 ± 17.3 and 51.1 ± 14.9, respectively) were assessed. CBD stones were detected by EUS overall in 17 (65.4%) patients: 61.5% of patients (8/13) in the intermediate likelihood- and 69.2% of patients (9/13) in the high likelihood group. The size and the number of detected CBD stones in all patients were confirmed by the followed therapeutic endoscopic retrograde cholangio-pancreatography (ERCP) except in one case where a preampullary calcific stenosis was described as a calculus during the EUS. Two-month follow up of those patients with no CBD stones detected on EUS revealed no clinical findings suspicious for biliary obstruction.

Conclusion: EUS is a highly sensitive and accurate diagnostic tool for the detection and evaluation of CBD stones also in patients with previous normal USG findings. Further study is needed to assess the potential correlation of clinical data with EUS findings in the detection of suspected choledocholithiasis.

Disclosure of Interest: None declared

P0228 MULTICENTRE RANDOMIZED TRIAL COMPARING EUS GUIDED FINE NEEDLE ASPIRATION CYTOLOGY (FNAC) WITH FINE NEEDLE ASPIRATION BIOPSY (FNAB) IN SAMPLING SOLID PANCREATIC MASS LESIONS: PRELIMINARY RESULTS FROM THE PROCORE TRIAL

J. Ortiz¹, M. Wireko¹, K. Ragunath¹, M. James¹, P. Kaye¹, K. Oppong², M. Nayar², A. Darne³, B. Mahon⁴, C. Forde⁴, P. Taniere⁴, G. Aithal¹

¹NIHR Nottingham Digestive Diseases Biomedical Research Unit at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, ²Freeman Hospital, ³Royal Victoria Infirmary, Newcastle-Upon-Tyne, ⁴Queen Elizabeth University Hospital Birmingham NHS Trust, Birmingham, United Kingdom

Contact E-mail Address: jacobo.ortizfernndezsordo@nottingham.ac.uk

Introduction: EUS-guided FNA is the standard of care for tissue sampling of pancreatic lesions. It has some limitations such as lack of proper histology sample, low sensitivity for malignancy in the presence of chronic pancreatitis, low diagnostic accuracy in the absence of on-site cytopathologist and false-positive rates up to 5-7%. The new Echo Tip ProCore biopsy needle (Cook Medical) was developed to obtain core tissue specimens improving the diagnostic yield and potentially obviating the need for onsite cytopathologist.

Aims & Methods: To compare the standard Echo tip ultra FNAC needle with the new Echo Tip Ultra ProCore FNAB needle in the sampling of solid pancreatic lesions. Sampling time, number of passes and sample adequacy were compared. Randomized multicenter trial in a tertiary university hospitals setting approved by the National Research Ethics Service (NRES). All patients referred for EUS guided tissue sampling of a solid pancreatic mass were invited to participate. Informed consent form was obtained from every participant. Linear EUS (Aloka-Olympus, Hitachi-Pentax) was performed and patients were randomised to either FNAC or FNAB. Due to the nature of the study the endoscopist could not be blinded. A 22G needle was used when sampling from the stomach and a 25G from the duodenum. A maximum of 5 passesº were allowed. Sampling time from first insertion of the needle into the lesion to the time the last sample is transferred into the histology pot, number of passes and adequacy for diagnosis reported by the pathologist were recorded and included for analysis. Immediate and delayed complications between days 8-30 post procedure were also recorded.

Results: 266 patients were recruited (median age 67 years, 52% men); 142 were randomized to FNAC and 124 to FNAB. Two were excluded after randomization; no mass lesion was seen in 1 patient randomized to FNAC and the needle failed in 1 patient in the FNAB group and FNAC was performed. A total of 264 patients were analyzed, FNAC=141 (22G=83 and 25G=58. Median lesion size 34 mm, range 10-87 mm) and FNAB=123 (22G=53 and 25G=71. Median lesion size 33 mm, range 8-85 mm). There was no statistical significant difference in number of passes (median 4, range 1-5 in the FNAC group vs. median 3, range 1-5 in the FNAB group, p=0.126), required time to obtain adequate samples (median 13 min, range 1-32 min vs. median 13 min, range 2-42 min, p=0.636) and adequacy of the specimen for diagnosis (90.8% vs. 87%, p=0.33). Three technical failures were observed in the FNAB cohort, 2 different needles had to be used in two patients as first was faulty and in 1 patient the needle did not come out from the scope (excluded for analysis). No technical failures noted in the FNAC cohort (1.6% vs. 0%, p=0.998). No immediate or delay complications reported in either group.

Conclusion: FNAC and FNAB needles were comparable in terms of sampling time, number of passes, sample adequacy for diagnosis and safety. Technical failure was higher in the FNAB arm but not statistically significant.

Disclosure of Interest: J. Ortiz: None declared, M. Wireko: None declared, K. Ragunath Financial support for research: Olympus-Keymed, Cook Medical and Covidien, Lecture fee(s): Olympus-Keymed, Cook Medical and Covidien, Consultancy: Olympus-Keymed, Cook Medical and Covidien, M. James: None declared, P. Kaye: None declared, K. Oppong: None declared, M. Nayar: None declared, A. Darne: None declared, B. Mahon: None declared, C. Forde: None declared, P. Taniere: None declared, G. Aithal: None declared

P0229 DIAGNOSTIC YIELD AND THERAPEUTIC IMPACT OF EMERGENCY CAPSULE ENTEROSCOPY IN ACTIVE-OVERT OBSCURE GASTROINTESTINAL BLEEDING

A. Ponte¹, R. Pinho¹, A. Rodrigues¹, T. Pinto-Pais¹, I. Ribeiro¹, J. Silva¹, J. Rodrigues¹, J. Carvalho¹

¹Gastroenterology, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal

Contact E-mail Address: ana.ilponte@gmail.com

Introduction: Capsule enteroscopy (CE) allows the evaluation of the entire small bowel, representing an important tool in the management of obscure gastrointestinal bleeding (OGIB).^1,2,3 Nevertheless, the real impact of CE in the management of active overt OGIB (OOGIB) lacks evidence.¹ The aim of this study was to evaluate the diagnostic yield of CE and its therapeutic impact in patients with active OOGIB.

Aims & Methods: Between April 2005 and January 2015, all patients with active OOGIB who underwent emergency CE in the first 48 hours after a negative esophagogastroduodenoscopy and ileocolonoscopy were included. Severe active OOGIB was classified as persistency of melena or hematochezia despite an initial negative endoscopic assessment, resulting in hemodynamic instability (systemic arterial pressure <100 mmHg and pulse >100 beats/min) and/or the need for ≥2 units of packed red blood cells (PRBC). Patients with active OOGIB not fulfilling the preceding criteria were classified as mild-to-moderate. Descriptive analysis was performed.

Results: 42 patients underwent emergency CE, 50% were men with a mean age of 61.7 years. The mean hemoglobin at admission was 9.0+/-2.9 g/dL and 59.5% (n=25) required PRBC transfusion, with a mean number of 1.4 units. OOGIB manifested with melena in 59.5% (n=25) of patients and with hematochezia in 40.5% (n=17) and was classified as severe in 59.5% (n=25) and as mild-to-moderate in 40.5% (n=17). CE identified a lesion in 52.4% (n=22) patients with active OOGIB (n=14 severe; n=8 mild-to-moderate) and identified the location of bleeding in 38.1% (n=16) of active OOGIB (n=9 severe; n=7 mild-to-moderate), totaling a diagnostic yield of 90.5% in active OOGIB (92% in severe; 88.3% in mild-to-moderate). Findings included active bleeding (n=15); ulcers/erosions (n=7); angiodysplasias (n=6); tumors (n=4); Meckel’s diverticulum (n=2); polyps (n=2); signs of recent bleeding (n=1); varices (n=1). Further diagnostic and therapeutic procedures were performed in 73.8% patients, including endoscopy in 38.1%, surgery in 19%, endoscopy/surgery in 7.1%, endoscopy/radiology in 4.8%; radiology/surgery in 2.4% and radiology in 2.4%.

Conclusion: The diagnostic yield of emergency CE was 90.5%, establishing the diagnosis in 52.4% of the patients and identifying the location of bleeding in more 38.1%, resulting in a specific management in 73.8% of cases. This study highlights the importance of emergency CE in the diagnostic approach and subsequent therapeutic management in active OOGIB.

Disclosure of Interest: None declared

P0230 ROLE OF ENDOSCOPIC CAPSULE IN PATIENTS WITH CHRONIC DIARRHEA AND ABDOMINAL PAIN OF UNKNOWN ORIGIN

C. Robles-Medranda¹, G. Bravo¹, J. Ospina¹, M. Soria¹, R. Del Valle¹, H. Pitanga Lukashok¹

¹Endoscopy, Instituto Ecuatoriano De Enfermedades Digestivas, University Hospital Omni, Espiritu Santo University, Guayaquil, Ecuador

Contact E-mail Address: carlosoakm@yahoo.es

Introduction: Capsule endoscopy (CE) is a diagnostic method that enables visualization of intraluminal bowel, diagnosing disorders not diagnosed effectively.

Aims & Methods

Aim: To demonstrate the utility and diagnostic effectiveness of CE in patients with diarrhea and initially diagnosed and treated as irritable bowel syndrome and abdominal pain.

Methods: Retrospective study (03-2012 / 03-2014) in patients who underwent CE for abdominal pain and / or diarrhea, normal studies: gastroscopy, colonoscopy and laboratory; patients without improvement, previously treated as IBS according to Rome III criteria. We used 2 type of capsules: Mirocam (Intromedic) and SB2 (Given-Imaging).Readings were performed by a single physician who is blinded for the study.

Results: 216 CE were reveiwed. 65 (30%) subjects met the criteria. (35/65) or 53.8% were women. Median age was 50 years. Diarrhea was present in 33.8% (22/65) and abdominal pain in 66.1% (43/65). CE with diarrhea subjects showed: atrophy of the villi in 18.1% (4/22), and ulcers compatible with inflammatory bowel disease (IBD) 36.3% (n = 8/22), normal study in 45.4% (n = 10/22). CE in -abdominal pain subjects detected: ascaridiasis 2.3% (n=1/43), atrophy of villi in 23.2% (n=10/43), IBD in 25.5% (n=11/43), gastroparesis in 6.9% (n = 3/43), submucosal tumor 2.3% (n = 1/43), nonspecific erythema 4.65% (n=2). In total, the CE detected 48% more lesions that had a clinical impact of 100%.

Conclusion: The CE showed an important role in managing IBS patients with no response to treatment.

Disclosure of Interest: None declared

P0231 PREDICTING INFLAMMATORY PATHOLOGY AT CAPSULE ENTEROSCOPY: WHAT IS THE UTILITY OF A RAISED FAECAL CALPROTECTIN?

C. Parker¹, C. Lamb¹, M. Robinson¹, J. Mansfield¹, M. Gunn¹

¹Gastroenterology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom

Contact E-mail Address: clare.e.parker@doctors.net.uk

Introduction: Faecal Calprotectin (FCP) is a widely used biomarker of gastrointestinal (GI) mucosal inflammation. Many capsule enteroscopy (CE) services are receiving increased referrals of patients with abdominal symptoms combined with an elevated FCP (>50µg/g) but normal gastroscopy, colonoscopy or radiology. There is little data on using FCP levels as a screening tool for selecting patients in whom CE will lead to a definitive diagnosis. Elevated FCP levels may indiscriminately drive investigations in endoscopy and imaging-negative patients who subsequently have normal findings at CE. We aimed to determine the incidence of inflammatory pathology on CE in patients with a raised FCP, and if a suitable concentration of the biomarker could be identified as a screening tool to avoid unnecessary CE.

Aims & Methods: A single centre retrospective review of The Newcastle upon Tyne Hospitals CE database was conducted (Feb 2012-Feb 2015). Patients with GI symptoms (abdominal pain, diarrhoea, bloating, vomiting, weight loss) and a raised FCP (>50µg/g) were identified. Findings at CE considered to be inflammatory were: erythema, ulceration, erosions and fissuring.

Results: 35 patients were identified with elevated FCP and GI symptoms. 45.7% (n=16) had inflammation identified by CE and in 54.3% (n=19) no inflammatory pathology was identified. The mean (+/-SE) FCP was higher in patients with evidence of inflammation at CE in comparison to those with no inflammation: 452.1(95.8)µg/g vs. 206(20.8)µg/g; p=0.01. Stratifying patients according to FCP revealed that only 8.3% of patients (n=1/12) with a FCP of 50-200µg/g had inflammatory findings at CE. This rose to 58.3% of patients (n=7/12) with a FCP of 201-300µg/g, and 72.7% of patients (n=8/11) with a FCP >300µg/g. A threshold of 200µg/g FCP revealed a sensitivity of 94.1% to predict inflammation at CE, with a specificity of 55.6%. This FCP threshold had a negative predictive value of 90.9%, and positive predictive value of 66.7% for CE inflammation.

Conclusion: In this small retrospective analysis of a sub-group of patients referred for CE with a FCP of >50μg/g the likelihood of identifying inflammatory pathology at CE increased with rising FCP concentrations above 200μg/g. A threshold of 200μg/g provided a high negative predictive value for CE inflammation and may be a useful screening tool to reduce the requirement for CE in select patient groups. This retrospective analysis should be confirmed in a larger prospective cohort.

Disclosure of Interest: None declared

P0232 ROLE OF SECOND-GENERATION COLON CAPSULE ENDOSCOPY FOR WHOLE GUT EVALUATION

C. Spada¹, C. Hassan¹, M. Campanale¹, L. Petruzziello¹, G. Costamagna¹

¹Digestive Endoscopy Unit, Catholic University of Rome, Rome, Italy

Contact E-mail Address: chiaracampanale@hotmail.com

Introduction: Although colon capsule endoscopy (CCE) was developed for evaluation of the colon, it can be used to assess the entire GI tract since it offers excellent images also of the esophagus and the small bowel (SB), with the exception of the stomach that remains poorly evaluated. Usually, after the firsts 3 min of running, CCE slows down the frame rate to 14 images/min. When SB is detected CCE automatically restarts using the Adaptive Frame Rate (AFR) technology. Nevertheless, CCE can be also “activated” to the AFR mode prior to the ingestion allowing the whole gut evaluation at a high frame rate acquisition.

Aims & Methods: Aim of this preliminary, feasibility study was to evaluate the ability of CCE to evaluate esophagus, small bowel and colon if patients take CCE after early, manual activation. Methods: 19 pts (8F, mean age 58 yrs, R 31-78 yrs) were enrolled. All pts underwent second-generation CCE. Pts were invited to follow the standard regimen of preparation for CCE. It consists of the regimen recommended by the ESGE guidelines with the inclusion of Gastrografin in adjunct to sodium phosphate booster. The day of the procedure all CCE were manually activated to AFR before the ingestion. Pts were asked to swallow CCE following the recommended procedure for ESO capsule. They remained in hospital until CCE transit into the SB was confirmed. They were, then, invited to drink the first booster and leave the hospital. Esophageal, SB and colonic transit times (TT) were evaluated. Esophagoscopy was defined complete when Z line was visualized. Completeness and cleansing level of SB and colon were evaluated. Significant findings were defined as findings that could explain the reason for referral and/or that had any effect on the medical decision making.

Results: Indication for CE was: incomplete colonoscopy (n=7), OGIB (6), colonoscopy refusal (4), iron deficiency anemia (2). A total evaluation of the entire GI tract was possible in 14 out of 19 pts (74%): Z line was not visualized in 4 pts and colonoscopy was incomplete in 1. Overall the Z line was visualized in 15/19 (79%) pts. Mean esophageal capsule TT was 69 sec (R 5-497). 1 (5%) pt had esophagitis. Complete capsule enteroscopy and SB adequate cleansing level was achieved in all pts. Mean SBTT was 106 min (R38-231). Significant SB findings were diagnosed in 3 (16%) pts and included diverticula (1), ulcerations (1) and large bleeding polyp (1). Colon TT was 104 min (R 10 734). CCE was complete and cleansing level was adequate in 18/19 (95%) pts. Significant findings were diagnosed in 6 (31%) pts: ≥6mm/≥3 polyps (5) and caecal angiodysplasia (1).

Conclusion: Second-generation CCE is feasible for whole GI evaluation and it has a relevant impact on medical decision making. The indications for a pan-endoscopy, however, need to be clarified and the procedure should be validated.

Disclosure of Interest: None declared

P0233 UPPER AND LOWER GASTROINTESTINAL LESIONS OVERLOOKED AT CONVENTIONAL ENDOSCOPY AND FURTHER DIAGNOSED WITH SMALL BOWEL CAPSULE ENDOSCOPY: THE CRUCIAL ROLE OF ENDOSCOPIC EXPERIENCE IN PATIENTS WITH OBSCURE GASTROINTESTINAL BLEEDING

D. Moneghini¹, G. Missale¹, L. Minelli¹, R. Cestari¹

¹Digestive Endoscopy, Spedali Civili - University of Brescia, Brescia, Italy

Contact E-mail Address: dario.moneghini@spedalicivili.brescia.it

Introduction: The role of small bowel capsule endoscopy (CE) in the investigation of obscure gastrointestinal bleeding (OGIB) is well established, with a mean diagnostic yield of 60%. However, in up to 20% of patients the cause of OGIB is located within the reach of upper and lower endoscopy. No data are available regarding the impact of endoscopic experience on the rate of lesions missed by previous esophagogastroduodenoscopy (EGDS) or ileocolonoscopy (ICS) and further found with CE. The aim of this series is to clarify if the experience of the endoscopy units could influence the rate of overlooked lesions.

Aims & Methods: We retrospectively reviewed the charts of 584 patients who underwent CE at Endoscopy Unit between October 2008 and March 2015 for OGIB. The CE-derived data are recorded and analyzed in terms of non-small-bowel CE findings (gastric, duodenal and colonic lesions) overlooked at previous upper and lower endoscopy. The type of endoscopic units who performed the conventional endoscopy (tertiary referral centres or primary level centres) and the respective lesions miss rate was recorded. The Given M2A video capsule system (Pillcam; Given Imaging Ltd, Yoqneam, Israel) was used. The day before the exam bowel preparation with 2L of polyethylene glycol solution was administered. Capsule ingestion was performed in the morning after a overnight fast. All the patients gave their written informed consent.

Results: 547 patients were enrolled for the final investigation (41 cases were excluded from further analysis because of the capsule did not reach the colon). In 35 patients (6.4%) one or more lesions previously missed by conventional endoscopy were diagnosed at CE. 20 of these 35 cases were males. The mean age was 72.8 years (range 51-89). 77.1% of lesions were overlooked at primary level endoscopy units; 22.9% at tertiary level units (p < 0.01). The overlooked lesions are reported in the table according to the type of endoscopic centre. The most frequently missed lesions were located in stomach and duodenum (66.6%); primary centres missed lesions mostly during EGDS (71.4%); tertiary centres miss lesions during EGDS and ICS equally. Both types of centres can miss neoplasias (66.6% at primary centres): tertiary centre overlooked a gastric GIST (gastrointestinal stromal tumor); primary centres overlooked a non invasive intraepithelial gastric haemorrhagic neoplasia and an ascending colon adenocarcinoma.

Abstract number: P0233

	Gastric angioectasia	Gastrojejunal anastomosis haemorrhagic erosions	GAVE	Gastric neoplasia	Erosive haemorrhagic gastritis	Gastric ulcer	Gastric Dielafoy’s lesion	Duodenal angioectasia	Duodenal Dielafoy’s lesion	Duodenal varix	Erosive haemorrhagic duodenitis	Colonic Angioectasia	Colonic polyp	Colonic neoplasia
Primary Endoscopy	1	2	2	1	1	1	1	7	2	1	1	6	1	1
Tertiary Endoscopy	1	-	-	1	1	-	-	1	-	-	-	4	-	-

Conclusion: Our results suggest that endoscopic experience, in terms of number of referral patients, can significantly reduce the miss rate of lesions located in upper or lower gastrointestinal tract, avoiding unhelpful CE.

Disclosure of Interest: None declared

P0234 COLON CAPSULE TRANSIT TIMES AND IMAGE QUALITY IN PATIENTS PREPARED WITH POLYETHYLENE GLYCOL + ASCORBATE (PEG + A) AND BOOSTER OF EITHER PEG + A OR GASTROGRAFIN AND LOW DOSE SODIUM PHOSPHATE (NAP)

D. Nastou¹, H. Palmer¹, J. Lewandowski¹, O. Epstein¹

¹Minimally Invasive Gastroenterology, Royal Free Hospital, London, United Kingdom

Contact E-mail Address: desnastos@yahoo.gr

Introduction: Successful colon capsule endoscopy (CCE) requires high capsule excretion rates and high-quality bowel cleansing. Most cleansing regimens are based on polyethylene glycol (PEG) supplemented with a booster of NaP to accelerate transit time. Because of potential renal toxicity associated with NaP, we have piloted two novel CCE cleansing regimens.

Aims & Methods: Prep1 was designed as a NaP free regimen comprising 2L PEG + Ascorbate (PEG + A) administered as a split dose, with an additional 1L booster after capsule ingestion. Prep2 comprised identical split dose 2L PEG + A, but the post capsule ingestion booster was low dose NaP (30-45ml) and gastrografin (50-100ml), a contrast medium known to accelerate bowel transit. 34 CCEs were reviewed, 17 from each group. Oro-caecal, caeco-rectal transit times and capsule excretion rates were measured. Quality of bowel cleansing was assessed by two independent observers, using a modified small bowel cleansing scale grading from the first caecal image and every 15 minutes until the end of the study. At each time point the assessors graded each of the two static images recorded by the CCE cameras. The proportion of visualised mucosa was graded as M3 (>75% of mucosal surface visualised), M2 (50-75%), M1 (25-49%) and M0 (<25%). Obscuration was graded as O3 (<5% of the image obscured by bubbles, debris or unclear fluids), O2 (5-24%), O1 (25-50%) and O0 (>50%). If capsule remained stationary more than 15 minutes, the time was extended to the frame 15 minutes following onward movement of capsule.

Results: In 6 of the 17 CCEs (35.29%) assessed in prep1 group, the capsule camera was excreted, providing a complete assessment of the colonic mucosa. The excreted capsule cameras for the prep2 group were 15 of 17 (88.23%) (p=0.001).

Three hundred seventy five frames were assessed and graded from the group that received prep 1. Three hundred sixty six frames were assessed and graded from the group that received prep 2.

In total 55.4% of frames in prep1 group scored M2/M3 for mucosal visualisation (equivalent to good/excellent bowel preparation as described by standard CCE grading scores), whilst in prep2 group 82.23% of frames scored M2/M3 (p < 0.001).

In prep1 group 24.53% of frames scored O3 for obscuration (equivalent to insignificant obscuration with standard CCE scores), whilst in prep2 group 40.71% of total frames scored O3 (p < 0.001).

Conclusion: Prep1 assessed whether a PEG + A booster could produce a “tsunami” prokinetic cleansing effect and Prep2 examined boosting with a combination of gastrografin and low-dose NaP. Failure of capsule excretion occurred in almost two thirds of Prep1 patients, whilst with Prep2 the 88.2% completion rate was similar to that expected in standard colonoscopy. In Prep1 group 55% of frames examined scored M2/M3 for mucosal visualisation and 43% O2/O3 for obscuration, whilst in Prep2 group 82% of frames scored M2/M3 and 72% O2/O3.

PEG + A is an ineffective booster and fails to achieve adequate cleansing whilst the booster combination of gastrografin and low dose NaP appears to offer both excellent excretion rates and enhanced bowel cleansing.

Disclosure of Interest: None declared

P0235 COLON CAPSULE ENDOSCOPY FOR THE PATIENTS WHO REFUSED STANDARD COLONOSCOPY

E. Ivanova¹², E. Fedorov¹, A. Avakimyan², E. Tikhomirova¹

¹Endoscopy, Moscow University Hospital №31, Moscow, ²Endoscopy, Klinika A, Krasnodar, Russian Federation

Contact E-mail Address: katendo@yandex.ru

Introduction: Colon capsule endoscopy (CCE) is an attractive alternative for the patients who refuse the standard colonoscopy.

Aims & Methods: To evaluate technical aspects and feasibility of CCE in the daily clinical practice. From I.2014 to XII.2014 we performed 57 CCE (PillCam Colon2) in 56 patients (m-26, f-30, mean age 51.4 ± 11.7 years, range 26-75). In 1 (2.7%) case the capsule retained in the stomach for 10 hours, so we repeated CCE once more. The main indication for colonoscopy was CRC screening – 37 (66.1%) patients; complaints of pain and constipation – 18 (32.1%); surveillance – 1 (1.8%) patient. The majority (96.4%) of patients refused to perform conventional, including sedated, colonoscopy. For the bowel preparation, we used regimen recommended by ESGE guidelines; for the evaluation of preparation – J.A.Leighton scale.

Results: Total CCE was performed in 52 (92.8%) patients. Slow capsule transit in sigmoid colon (until the battery exhausted) was observed in 3 (5.3%) patients, in transverse colon – in 1 (1.8%) patient. The mean transit time of the colon-capsule through the gastrointestinal tract was 7 hours 58 min ± 3 hours 33 min. The mean colon transit time was 6 hours 18 min ± 3 hours 04 min. Only 64.3% of the capsules were excreted in conditional 10 hours after ingestion. Colon preparation in 20 (35.7%) patients was excellent, in 25 (44.6%) - good, in 8(14.3%) – fair, in 3(5.4%) – poor. Colon abnormality was detected in 48 (85.7%) patients: polyps in 29 (60.4%), in 13 cases the size of polyps ranged from 1 to 6 mm, in 16 - was more than 6 mm; diverticulosis in 14 (29.1%) patients; erosions in 5 (10.4%); focal inflammation in 8 (16.6%); angioectasias in 6 (12.5%); melanosis in 1 (2.1%); aphtous ulcers in 7 (14.6%); anal fissure in 1 (2.1%) and hemorrhoids in 11 (22.9%) patients. No adverse events related to CCE were revealed. After CCE we recommended colonoscopy for 23 patients, but at the moment only 7 (30.4%) agreed. Results of CCE were completely confirmed in 3(42.8%) patients, partially – in 3(42.8%) and non-confirmed in 1(14.4%).

Conclusion: CCE was able to examine the whole large bowel in 92.8% of patients and to detect abnormalities in 85.7%, including polyps in 60.4% of patients. With reduced rates CCE could become the method of choice for CRC screening and incomplete colonoscopy.

Disclosure of Interest: None declared

P0236 MALE GENDER, PRESENCE OF ANGIODYSPLASIAS AND SMALL BOWEL POLYPS ARE RELATED WITH POORER BOWEL PREPARATION IN SMALL BOWEL ENDOSCOPY

P. Tsibouris¹, P. Apostolopoulos¹, C. Kalantzis¹, E. Chouda¹, E. Vlachou¹, G. Alexandrakis¹

¹Gastroenterology, Nimts General Hospital, Athens, Greece

Contact E-mail Address: tsibofam@yahoo.com

Introduction: Polyethylenoglucol has been widely used as bowel preparation before small bowel capsule endoscopy.

Aims & Methods

Aim: To determine risk factors those affect small bowel preparation with polyethilenoglycol.

Methods: 1030 patients undergone small bowel capsule endoscopy, gastroscopy and colonoscopy were evaluated. 165 with inflammatory bowel disease, 11 with celiac disease and 124 with underlined neoplasia were excluded from the analysis. 401 were evaluated for iron deficiency anemia, 149 for undefined gastrointestinal bleeding, 178 for diarrhea, 102 for other causes. Bowel preparation quality was defined as adequate (good, fair) or inadequate (poor). Stat: t-test, X2, logistic regression analysis.

Results: Bowel preparation was adequate in 533 (64.2%) patients. Mean age: adequate preparation: 63 ± 18 years, inadequate preparation: 63 ± 19 years (p=1.00); Preparation was adequate in: Gastrointestinal bleeding: 93 (62.4%), anemia: 249 (62.1%), other indications for capsule endoscopy: 191 (68.2%, not statistical difference for capsule endoscopy indication); Male gender: 277 (59%, p=0.004), active smoking: 119 (69%, p=0.20), alcohol consumption: 46 (55%, p=0.08); Small bowel polyps: 49.3%), small bowel ulcerative lesions: 142 (67.3%, p=0.28), small bowel ulcers: 36 (59%, p=0.37), angiodysplasias: 154 (57.5%, p=0.005); Diabetes mellitus: 107 (55.7%, p=0.005), motility disorders 12 (60%, p=0.69), ischemic heart disease 150 (58.8%, p=0.03), stroke 21 (60%, p=0.59), hypothyroidism 74 (66.1%, p=0.66), chronic renal failure 21 (48.8%, p=0.03), use of antidepressants 42 (63.6%), use of tranquillizers: 78 (63.9%, p=0.005). Moreover in patients excluded preparation was adequate in 7 (53.8%, p=0.44) of patients with small bowel cancers. Small bowel transit time in patients with adequate preparation was 332 ± 142 min, while in those with inadequate preparation was 355 ± 137 min (p=0.02). Capsule study completion was 78.2% in those with adequate preparation and 77.1% with those with inadequate (p=0.71). In logistic regression analysis: male gender (p=0.009), presence of angiodysplasias (p=0.048) and presence of small bowel polyps (p=0.03) predispose to inadequate bowel preparation.

Conclusion: Inadequate preparation is related with male gender, presence of angiodysplasias and small bowel polyps. The former possibly due to underline pathologies like diabetes or ischemic heart disease, while the latter two as they predispose to slower bowel transit. More thorough preparation is needed for those patient groups.

Disclosure of Interest: None declared

P0237 CAPSULE ENDOSCOPY IN PEDIATRIC PATIENTS WITH ESTABLISHED AND SUSPECTED CROHN´S DISEASE: SINGLE-CENTER EXPERIENCE OF 180 PROCEDURES

A. Nemeth¹, G. Wurm Johansson¹, H. Thorlacius², D. Agardh³, E. Toth¹

¹Endoscopy Unit, Department of Gastroenterology, ²Department of Surgery, ³Pediatric gastroenterology, Skåne University Hospital, Lund University, Malmo, Sweden

Contact E-mail Address: ervin.toth@med.lu.se

Introduction: Capsule endoscopy is a non-invasive method that enables excellent visualization of the small-bowel mucosa. The method has been evaluated for detection of Crohn's lesions in the adult population but data about the method's clinical value for diagnosing Crohn's disease in a large pediatric clinical material is still scarce.

Aims & Methods: The aim of our study was to examine the impact and safety of capsule endoscopy performed in children and adolescents being investigated for established and suspected Crohn´s disease (CD) at a tertiary academic hospital in Scandinavia.

A retrospective, single-center study included 180 capsule endoscopy examinations in 169 consecutive patients between October 2003 and December 2014. Patients had a median age of 13 years (range 3-17 years) and the indications for capsule endoscopy were clinically suspected (125 cases, 69%) and established (55 cases, 31%) CD. Capsule endoscopy was performed with PillCam^TM SB (Given Imaging) capsule endoscopy system with 8-12 hours of registration without bowel preparation.

Results: 26 of 180 (14%) capsules were endoscopically placed in the duodenum. Patency capsule examinations were performed in 47 (26%) cases.

Capsule endoscopy detected findings consistent with CD in 71 (40%) examinations, 17 (9%) procedures showed minor changes but were not diagnostic for CD. 92 (51%) examinations displayed normal intestinal mucosa. In 30 of 180 (17%) procedures the capsule did not reach the colon during recording time and were defined as incomplete examinations.

A change in therapy was recommended in 53/180 (29%) patients based on capsule endoscopy results.

The most feared complication, capsule retention, occurred in only one (0.6%) patient with established CD.

Conclusion: Capsule endoscopy is a safe method in children with suspected and established CD. The result of capsule endoscopy often leads to a definitive diagnosis and have significant impact on the clinical management of pediatric patients with CD.

Disclosure of Interest: None declared

P0238 THE NEW 360° PANORAMIC-VIEWING CAPSULE ENDOSCOPY SYSTEM: RESULTS OF THE FIRST MULTICENTER, OBSERVATIONAL, STUDY

G. E. Tontini¹, F. Cavallaro¹, R. Marino², M. E. McAlindon³, E. Rondonotti⁴, A. Koulaouzidis⁵, P. Vitagliano⁶, G. Tosetti¹, L. Pastorelli¹⁷, M. Vecchi¹⁷

¹Gastroenterology and Digestive Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milano, ²Gastroenterology and Digestive Endoscopy Unit, AO Lodi, Lodi, Italy, ³Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, United Kingdom, ⁴Gastroenterology Unit, Ospedale Valduce, Como, Italy, ⁵Gastroenterology and Digestive Endoscopy Unit, The Royal Infirmary of Edinburgh, Edinburgh, United Kingdom, ⁶Digestive Endoscopy Unit, AO Melegnano, Melegnano, Milano, ⁷Department of Biomedical Sciences for Health, University of Milan, Milano, Italy

Contact E-mail Address: gianeugeniotontini@libero.it

Introduction: CapsoCam^® SV1 (CapsoVision Inc, Saratoga, USA) is a new small bowel capsule (SBC) with “panoramic view”, wire-free technology, and a long-lasting battery life. It is equipped with 4 high frame rate cameras (3-5 frames/second/camera), located at the side of the capsule, resulting in a very high number of acquired frames. Previous studies, comparing this device with frontal view SBCs, showed comparable operative and diagnostic performance [1-2].

Aims & Methods: Accordingly, we conducted a multicenter, observational study to assess the performance of CapsoCam^® SV1 in real-life clinical setting. Between January 2014 and April 2015, all consecutive patients undergoing SBC with CapsoCam^® SV1 in four Italian and two British Institutions were enrolled. All the identified findings were classified according to their bleeding probability and clinical significance, in line with Saurin classification [3], as P0: low probability; P1: intermediate probability; P2: high probability. Capsule endoscopy was defined as “positive” if at least one P2 finding was identified.

Results: Eighty-nine patients underwent SBC (49 men; median age ± SD: 66 ± 17 years, range: 15-86 years). 70/89 were referred for obscure GI bleeding (18 with overt and 52 with occult OGIB) and 19/89 for suspected (17) or established (2) Crohn’s disease (CD). One technical failure occurred - due to short battery life (270min) - leading to incomplete enteroscopy. 88/89 patients excreted and retrieved the capsule. One capsule was retained due to a neoplastic stricture, no acute obstruction occurred and retrieval was done at time of surgery.

The overall diagnostic yield (rate of positive tests) was 42.5%, whereas it was 43.5% for OGIB (50% for overt bleeding) and 38.8% for CD. The ampulla of Vater was identified in 40% of patients and the capsule explored the entire small bowel in 91% of patients.

In a per-lesion analysis, overall 328 findings were detected (P0: 43, P1: 119, P2: 166). Most of the lesions were located in the small bowel (273/328: 83.2%) and 55% of them were classified as P2. Interestingly, 47/328 (14.3%) and 8/328 (2.4%) lesions were detected in the upper and in the lower GI tract, 22 and 6 of them were classified as P2 respectively.

Conclusion: Our data suggest that even when used in the everyday clinical practice, CapsoCam^® SV1 has a detection rate and a safety profile comparable to other SBCs with frontal view.

Disclosure of Interest: None declared

P0239 COLLAGE MODE IS A VALID TIME SAVING TOOL TO ASSESS COLON CAPSULE ENDOSCOPY

J.-P. Linke¹, J. Albert¹, J. Masseli¹, A. Tal¹, J. Hausmann¹, N. Filmann¹, M. Philipper², M. Farnbacher³, M. Khoury⁴

¹Gastroenterology, University hospital Frankfurt, Frankfurt, ²Gastroenterology, Doctor´s office, Düsseldorf, ³Gastroenterology, Doctor´s office, Erlangen, ⁴Gastroenterology, Medical center Hochfranken, Hof, Germany

Contact E-mail Address: jan-peterlinke@web.de

Introduction: Colon capsule endoscopy (CCE) is a valid, non-invasive method to detect colon polyps. However, CCE is time consuming. We evaluated a software algorithm that might reduce investigation time.

Aims & Methods: 29 CCE videos (CCE-2, Covidien®) were analysed by blinded investigators using the “collage mode” (Rapid 8 software, Covidien®) by experienced (n=3; two-day training course for detecting polyps in CCE and experience of at least 50 CCE investigations) and unexperienced investigators (n=3, twenty minute briefing about morphology of polyps and technique of CCE). Gold standard was the finding of an experienced extern investigator (>100 CCE) and results of subsequent flexible colonoscopy. Localisation of the entry to the colon and all detected polyps were marked. Videos were assessed under standardized conditions without interruption.

Results: Evaluation of CCE videos took 7.1 and 7.7 min for experienced and unexperienced investigators, respectively.

Sensitivity of experienced investigators was significantly higher than sensitivity of unexperienced investigators to detect at least one polyp, but specificity was similar in both groups see table 1.

Table 1.

Sensitivity and specificity of using the collage mode for detecting at least one colonic polyp per patient.

n= 29	experienced investigators	unexperienced investigators
Sensitivity	88.1+/-8.25%	56.96+/-30.82%
Specificity	84.86+/-7.36%	86.67+/-11.54%
Investigation time  per CCE video	424+/-198 sec.	458+/-229 sec.

Conclusion: The use of collage mode reduces the time to investigate colon capsule videos to less than eight minutes. Experienced investigators using this tool are able to achieve excellent sensitivity.

Disclosure of Interest: None declared

P0240 SINGLE-VISIT MEASURES OF GUT TRANSIT AND POSTPRANDIAL GASTRO-INTESTINAL MOTILITY USING MRI METHODOLOGY: A FEASIBILITY STUDY

C. L. Hoad¹, A. Khalaf², A. Menys³, A. Nowak², S. Paparo², S. A. Taylor³, R. C. Spiller², L. Marciani², P. A. Gowland¹, G. Moran²

¹Sir Peter Mansfield Imaging Centre, ²NIHR Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, ³Centre for Medical Imaging, Division of Medicine, UCL, London, United Kingdom

Contact E-mail Address: gordon.moran@nottingham.ac.uk

Introduction: Symptoms related to intestinal motility are common in irritable bowel syndrome and even inflammatory bowel disease. Patient symptoms of bloating and nausea are typically worse post-prandially but clinical investigations to date are carried out fasting or after aggressive and unpleasant bowel preparations likely to alter physiology. Moreover, different appointments necessitating multiple patient visits are usually needed to assess motility across different segments of the gastrointestinal (GI) tract.

Aims & Methods

Aims: We describe here a novel paradigm to assess fasting and postprandial motility in a single visit and assess its feasibility in healthy volunteers. The paradigm uses a validated soup meal¹, and MRI to measure gastric emptying², gall bladder contraction³, small bowel motility⁴, small bowel water content⁵ and whole gut transit⁶ in this cohort.

Methods: Ten healthy participants (5 male, age 32 (11) yrs) were recruited for this study MRI scanning was carried out on a 1.5T Philips Achieva scanner. The subjects were asked to swallow five MRI transit marker capsules (20 mm x 7 mm) at 09:00 am, 24 h before undergoing an MRI scan⁶ and fasted from 2000 h the night before. On the day of the scan, a baseline fasting scan at 0900 hours was acquired. At 0925 hours, subjects were asked to consume a soup meal (Heinz cream of chicken 204 kcal, 11.8g fat or mushroom soup 214 kcal, 11.4g, 400g) within 20 min with the first immediate postprandial scan acquired at 0945 hours. Data collection time points were every 15 min for the first 60 min and every 30 min up to 270 min. At each time point scans were acquired to assess gastric volume, gall bladder volume, small bowel water content and small bowel motility, 2 additional scans were acquired at baseline to determine the position of the transit pills.

Results: Data is presented as mean (standard deviation (SD)). All participants completed the study. In the immediate postprandial state, the gastric volume was 416 (73) mL. The mean half-life of the meal in the stomach was 41 (20) min. The gall bladder maximum ejection fraction was 59 (19) % which occurred within the first 60 minutes postprandially. The fasted small bowel contained a total volume of 41 (27) mL of resting water. Postprandially this small bowel water content rose to a maximum value of 107 (46) mL. Across the 10 volunteers, a motility index based on the SD of signal intensity across the small bowel rose by 47 (30) % postprandially . The mean whole gut transit as measured through a weighted average position score⁶ was 1.9 (1.5).

Conclusion: This novel paradigm is feasible and well tolerated by participants. The soup meal challenge was effective in inducing a change in multiple measured end-points, monitoring markers of GI motility in a single visit. This methodology may be applied to a variety of disease groups to understand alterations in GI physiology, allowing us to identify symptom biomarkers to target pharmacologically.

Disclosure of Interest: C. Hoad: None declared, A. Khalaf: None declared, A. Menys Shareholder: Motilent Ltd, Directorship(s): Motilent Ltd, A. Nowak: None declared, S. Paparo: None declared, S. Taylor: None declared, R. Spiller: None declared, L. Marciani: None declared, P. Gowland: None declared, G. Moran: None declared

P0241 NOVEL PROBE-BASED QUANTATIVE IMAGE OF MITOCHONDRIA IN LIVE COLON CANCER TISSUES BY MULTIPHOTON MICROSCOPY

E. S. Kim¹, H. J. Chun¹, I. K. You¹, S. H. Kim¹, J. M. Lee¹, H. S. Choi¹, B. Keum¹, Y. T. Jeen¹

¹Gastroenterology, Korea University College of Medicine, Seoul, Republic of Korea

Contact E-mail Address: silverkes@naver.com

Introduction: Multiphoton endomicroscopy is the recentely updated technique for endoscopy and virtual image and optical sectioning. However optimized probe has not been established for multiphoton endomicroscopic image. Therefore we developed novel probe for mitochondria and applied for colon neoplasm tissues. In cancer cell, abnormally increased mitochondrial replication is related mitochondrial dysfunction and Warburg effect.[1]

Aims & Methods: We used newly developed multiphoton probe for micochondria imaging which are made using benzofuran derivative (BFP, maximal multiphoton fluorescence at 570 nm). Fresh mucosal tissues of colonic adenoma and adenocarcinoma were obtained from endoscopic biopsy. Multiphoton probe BFP for mitochondria was stained for tissues and imaging performed using multiphoton microscopy.

Results: BFP shows high enhancement factor upon binding mitochondria, good selectivity, cell permeability, and can readily detect mitochondria in human tissues by multiphoton microscopy. Mitochondria were detected in human colon mucosa tissues. Calculated mitochondria area were increased in adenocarcinoma tissues compared to normal mucosal tissues.

Conclusion: Newly developed multiphoton probe for mitochondria are usable to image human live colon tissues. Mitochondrias are increased in colon cancer tissues compared to normal colon mucosa tissues.

Disclosure of Interest: None declared

P0242 COMPARISON OF COMPUTED TOMOGRAPHY AND MAGNETIC RESONANCE IMAGING IN THE DISCRIMINATION OF INTRA- AND EXTRAPERITONEAL RECTAL CANCER: INITIAL EXPERIENCE ON 38 PATIENTS

M. Furnari¹, M. Revelli², F. Paparo³, L. Bacigalupo³, G. Binda⁴, E. Savarino⁵, G. Rollandi⁴

¹Di.M.I., Gastroenterology Unit, University of Genoa, Genoa, ²Department of Radiology, “San Bartolomeo” Hospital, ASL5, Sarzana, La Spezia, ³Department of Radiology, ⁴Unit of Hepatobiliary Surgery, Department of Abdominal Surgery, E.O. Ospedali Galliera, genoa, ⁵Unit of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, university of Padua, Padua, Italy

Introduction: Abdominal CT may have a role in the loco-regional evaluation of rectal cancer, besides systemic staging. The discrimination between intra- and extraperitoneal rectal cancer has important implications for both oncologic and surgical grounds. Indeed, based on intra- and extraperitoneal location the therapeutic approach may change because of the different risks of local recurrence and different prognosis.

Aims & Methods: Aim of the study was to compare the diagnostic performance of CT with that of MRI to determine the intra- or extraperitoneal location of rectal cancers, using surgical exploration as reference standard. We retrospectively evaluated MRI and CT examinations of patients with rectal cancer defining the extra- or intraperitoneal location of tumor’s inferior edge with respect to the anterior peritoneal reflection (APR). We assessed the quality of identification of the APR according to a 4-point confidence scale and we measured the distance from the inferior edge of tumors to the anal verge and from the APR to the anal verge.

Results: Thirty-eight patients were included: 24 men and 14 women with a mean age of 68.8 ± 9.4 years. The APR was appreciable in all MRI examinations and in 36/38 patients on CT images. Mean distances from the APR to the anal verge were 98.97 ± 18.8 mm at MR and 100.6 ± 12.9 mm at CT (p=0.6653, t-test for independent samples). MR showed sensitivity of 100% (95% CI: 89.62-100.00%), specificity of 75% (95% CI: 20.34-95.88%), positive predictive value of 97.14% (95% CI: 85.03-99.52%), negative predictive value of 100% (95% CI: 30.48-100.00%). Diagnostic performance of CT was: sensitivity 100% (95% CI: 89.32-100.00%), specificity 60% (95% CI: 15.40-93.51%), positive predictive value 94.29% (95% CI: 80.81-99.13%), negative predictive value 100% (95% CI: 30.48-100.00%). The mean distance from the inferior edge of tumors to the anal verge was 62.3 ± 21.2 mm at MR and 62.5 ± 20.1 mm at CT (p=0.8181 Mann-Whitney test for independent samples), with a strong correlation (Spearman's coefficient of rank correlation (rho): 0.995; p < 0.0001).

Conclusion: The results of our study confirm the great clinical value of MRI in determining the location of rectal cancers by direct visualization of APR in preoperative setting; CT demonstrated a potential supporting role in the evaluation of rectal cancer, showing a strong correlation with MRI in regarding measurements of the distance betweenthe tumor’s inferior edge and the anal verge.

Disclosure of Interest: None declared

P0243 ABDOMINAL ULTRASOUND FOR DIAGNOSIS OF ACUTE APPENDICITIS: SYSTEMATIC REVIEW AND META-ANALYSIS OF DIAGNOSTIC ACCURACY STUDIES

V. Giljaca¹, T. Nadarevic², G. Poropat¹, D. Stimac¹

¹Gastroenterology, ²Radiology, University Hospital Centre Rijeka, Rijeka, Croatia

Contact E-mail Address: vanja.giljaca@gmail.com

Introduction: Acute appendicitis (AA) is one of the most frequent causes of acute abdominal pain (1, 2). Clinical signs of AA have overall diagnostic accuracy for the disease of about 80% (3). Reported sensitivity and specificity of abdominal ultrasound (US) for diagnosis of AA is up to 92% and 96%, respectively (4, 5). The reported negative appendectomy rate is up to 34% (6, 7).

Aims & Methods: The aim of this systematic review was to determine diagnostic accuracy of US for diagnosis of AA. Medline, Embase, The Cochrane library and Science Citation Index Expanded from January 1994 to October 2014 were systematically searched. The reference standard for evaluation of final diagnosis was pathohistological report from the tissue obtained on appendectomy. Summary sensitivity, specificity and post-test probability of AA after positive and negative result of US with corresponding 95% confidence intervals (CI) were calculated. The pre-test probability was defined as the prevalence of AA in the population of included studies. Review Manager 5 (8) and METADAS macro for SAS were used for statistical analysis (9). Methodological quality of included studies was evaluated using Quality Assessment in Diagnostic Accuracy Studies 2 (QUADAS-2) tool (10).

Results: There were 3,306 references identified through electronic searches. Full-texts of 296 reports were assessed for inclusion, out of which 17 reports met the inclusion criteria. A total of 2,841 participants were included in the analysis. None of the included studies were of high methodological quality. The results of meta-analysis are presented in the Table. The result of sensitivity analysis did not significantly influence summary results of the main analysis.

Abstract number: P0243

Sensitivity	Specificity	Post-test probability for positive US result at prevalence 76.4%	Post-test probability for negative US result at prevalence 76.4%
69% (95% CI 59% to 78%)	81% (95% CI 73% to 88%)	92% (95% CI 88% to 95%)	55% (95% CI 46% to 63%)

Conclusion: Abdominal ultrasound does not seem to have a role in the diagnostic pathway for acute appendicitis. The sensitivity and specificity of US do not seem to exceed that of clinical examination. Patients with lower clinical probability of having AA that require additional diagnostic workup should be referred to more sensitive and specific diagnostic procedures, such as computed tomography.

Disclosure of Interest: None declared

P0244 ENDOSCOPIC MANAGEMENT OF TEMPORARY PLACEMENT OF FULLY COVERED SELF-EXPANDABLE METAL STENTS IN BENIGN BILIARY STRICTURES

D. Lacombe¹, C. E. C. P. Miranda², J. C. Ardengh³, J. F. E. Coelho⁴, D. E. Coelho¹

¹Surgery, Universidade Estácio de Sá - Hospital Municipal Lourenço Jorge, ²Surgery, Universidade Souza Marques, Rio de Janeiro, ³Surgery, Universidade de São Paulo - Faculdade de Medicina de Ribeirão Preto, São Paulo, ⁴Surgery, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

Contact E-mail Address: coelhodjlma@yahoo.com

Introduction

Background/Aims: Benign biliary strictures (BBSs) have been endoscopically managed with plastic stent placement. Fully covered self-expandable metal stents (FCSEMSs) are gaining acceptance for the treatment of BBSs. We performed a large prospective study to analyze the clinical outcomes; following endoscopic treatment data regarding fully covered self-expandable metal stents (FCSEMSs) in BBS patients remain scarce in Rio de Janeiro.

Aims & Methods: Methods: In a nonrandomized study a single center, 263 patients (145 men, 55%) with BBSs underwent FCSEMS placement between January 2012 and March 2015. Efficacy and safety were evaluated retrospectively. Patients were considered to have resolution if they showed evidence of stricture resolution on cholangiography and if an inflated retrieval balloon easily passed through the strictures at FCSEMS removal.

Results: The mean FCSEMS placement time was 6.2 (1.0-12.2) months. Patients were followed for a mean of 10.2 (1.0-36.0) months after FCSEMS removal. The BBS resolution rate was confirmed in 241 of 263 (92%) patients who underwent FCSEMS removal. After FCSEMS removal, 36 of 241 (15.8%) patients experienced symptomatic recurrent stricture and repeat stenting was performed. When a breakdown by etiology of stricture was performed, 17 of 20 (85%) patients with chronic pancreatitis, 53 of 53 (100%) with gall stone-related disease, 57 of 61 (93%) with surgical procedures, pancreatic collections 45 of 47 (93.3%), Endoscopic complications (perforation and bleeding) 14 of 14 (100%) and 55 of 68 (80%) with BBSs of other etiology had resolution at FCSEMS removal. Complications related to stent therapy occurred in 40 (15%) patients, including pain (n=23), proximal migration (n=10), cholecystitis (n= 1), distal migration (n=2), and occlusion (n=4).

Conclusion: Endoscopic treatment of temporary FCSEMS placement in BBS patients is safe and effective and can be considered a first-choice alternative to surgical and/or plastic stenting. The potential benefits and risks should be evaluated in further investigations.

Disclosure of Interest: None declared

P0245 USE OF PARTIALLY COVERED AND UNCOVERED METALLIC PROSTHESIS (GIOBOR STENT) FOR ENDOSCOPIC ULTRASOUND-GUIDED HEPATICOGASTROSTOMY: RESULTS OF A RETROSPECTIVE MONOCENTRIC STUDY

C. De Cassan¹, E. Bories¹, C. Pesenti¹, F. Caillol¹, S. Godat¹, J. P. Ratone¹, J. R. Delpero¹, M. Giovannini¹

¹Institut Paoli Calmettes, Marseille, France

Contact E-mail Address: chiaradecassan@gmail.com

Introduction: Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) represents an option to treat obstructive jaundice when endoscopic retrograde cholangio pancreatography (ERCP) fails, in alternative to surgery or percutaneous transhepatic biliary drainage (PTBD). The success rate of this technique has been shown to be very high, with resolution of jaundice in up to 98.5% of cases. Up to now plastic and covered or uncovered self-expandable metallic stents (SEMS) have been used, each of them presenting some limitations.

Aims & Methods: Aims of this study were to evaluate the technical and functional success of EUS-HGS using a dedicated biliary SEMS with a half covered part (GioBor stent- Taewoong Medical ®). We retrospectively reviewed data of patients who underwent EUS-HGS at our centre, with at least 6 months of follow up. Demographics, clinical and laboratory data were extracted from the patient’s charts and electronic records. Technical success was defined as the passage of the GioBor stent across the stomach, along with the flow of contrast medium and/or bile through the stent, while functional success as the decrease of bilirubin value of at least 25% of the pre-treatment value within the first week. The rate of early (in the first month after EUS-HGS) and late (at 6 months follow up) complications was assessed.

Results: A total of 41 patients were included (21F/20M, mean age 66, range 45-65). Obstructive jaundice was due in most of patients (39/41, 95%) to a malignant disease. Reasons to EUS-HGS were failed biliary cannulation in 18 patients (44%) and failed bile duct decompression in 24 patients (56%). Technical success was obtained in 37/41 patients (90%), while functional success, measurable in only 29 patients, was obtained in 19/29 patients (65%). Thirteen patients (33%) presented an early complication, mostly represented by infectious complications. At six months follow up, 10/37 patients (27%) required a new biliary drainage and 11/37 (30%) died because of their disease.

Conclusion: EUS-HGS using GioBor stent is technically feasible, clinical effective, safe and may be an alternative to PTBD in case of ERCP failure for biliary decompression. Randomized controlled studies comparing GioBor prosthesis with “classical” SEMS are needed to confirm these preliminary results.

Disclosure of Interest: None declared

P0247 COVERED SELF-EXPANDABLE METALLIC STENT WITH LOW AXIAL FORCE FOR UNRESECTABLE MALIGNANT BILIARY OBSTRUCTION

K. Saito¹, M. Matsuyama¹, R. Kanata¹, I. Yamada¹, T. Sasaki¹, M. Ozaka¹, K. Takano¹, N. Sasahira¹

¹Department of Gastroenterology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan

Contact E-mail Address: kei.saito1006@gmail.com

Introduction: Although covered self-expandable metallic stent (SEMS) has longer patency than uncovered SEMS in patients with unresectable malignant distal biliary obstruction, the complication rate of covered SEMS are quite different among the stents due to their mechanical properties. Niti-S SUPREMO (Tae Woong Medical) is a newly developed fully-covered SEMS with lower axial force than a standard Covered WallFlex (Boston Scientific) stent.

Aims & Methods: We retrospectively analyzed the outcome of both types of covered SEMS in patients with unresectable malignant distal biliary obstruction. Medical records were retrospectively reviewed for consecutive patients with unresectable malignant distal biliary obstruction who underwent placement of Covered WallFlex between April 2009 and March 2011 (group W) and Niti-S SUPREMO 10 between April 2011 and June 2014 (group S). Background characteristics, procedure-related complications and long-term stent dysfunction were compared between the groups.

Results: Seventy-one patients were analyzed (25 vs. 46 in group W vs. group S, respectively). There were no significant differences in patient characteristics; median age of 65 vs. 67, male gender in 52% vs. 52%, perfomance status of 0 in 64% vs. 67%, pancreatic cancer in 93% vs. 94%, and receiving chemotherapy in 78% vs. 93%. Procedure-related complications were significantly higher in group W; acute pancreatitis in 8% vs. 0% (p=0.04) and acute cholecystitis in 12% vs. 0% (p=0.01). Stent dysfunction were seen in 16% vs. 28% (p=0.27) and median time to stent dysfunction by Kaplan-Meier method were 196 days vs. 150 days (p=0.50 by log-rank test). The median overall survival time were 259 days vs. 244 days (p=0.84).

Conclusion: Niti-S SUPREMO, a newly developed covered SEMS with lower axial force, decreased the risk of procedure related complications of acute pancreatitis and acute cholecystitis compared with covered WallFlex without significant differences in long-term outcomes.

Disclosure of Interest: None declared

P0248 EVALUATION OF ANTI-MIGRATION PROPERTIES OF BILIARY COVERED SELF-EXPANDABLE METAL STENTS

K. Minaga¹, M. Kitano¹, Y. Harwani¹, H. Imai¹, K. Kamata¹, T. Miyata¹, K. Yamao¹, K. Kadosaka¹, S. Omoto¹, M. Kudo¹

¹Department of Gastroenterology and Hepatology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan

Contact E-mail Address: m-kitano@med.kindai.ac.jp

Introduction: Endoscopic placement of self expandable metal stents (SEMSs) has been pivotal in providing relief from obstructive jaundice in patients with biliary stricture. Covered SEMSs tend to show a higher rate of stent migration than uncovered SEMSs, which is the most important issue to be resolved during deployment of the covered SEMSs for biliary stricture. Stent properties such as the stent framework, flare structure and radial force (RF) may prevent stent migration.

Aims & Methods: The purpose of the study was to measure the anti-migration potential of 6 different covered SEMSs including 5 braided types and one laser-cut type using a phantom model inducing migration of biliary SEMSs, and to evaluate whether RF and flare structure contribute to the anti-migration potential.

Anti-migration potential was measured using a phantom model for migration. The metal stents were fixed at a round hole of silicone walls of three types of hole diameter, 6, 8 and 10 mm. The distal end of the stent was fixed at a force gauge device. During experiments, the distal end of the stent with the force gauge device was retracted at a speed of 1mm/sec. using the retraction robot. The force of the resistance of the stent to the retraction (resistance force to migration; RFM) was measured from starting retraction of the stent to dislocating the distal end of the stent from the silicone wall.

The RF was measured by using a radial force measurement machine when the stent was compressed to 6, 8 and 10 mm in outer stent diameter.Three variables of stent flare structure including outer diameter of the flare (ODF), height of the flare (HF) and taper angle of the flare (TAF) were measured. The correlations between RF and RFM as well as between variables of the stent flare structure and RFM were analyzed.

Results: The smaller the compressed outer diameter of the stent (CODS), the higher the RFM and RF exhibited for all the 6 SEMSs. The laser-cut SEMS has higher RFM than any braided SEMSs whether the stent fully expands or not. A strong correlation between RF and RFM was observed when CODS was 6 mm (r = 0.849), but there was no strong correlation when the CODS was 8 or 10 mm. In addition, when the stent fully expanded (CODS was 10 mm), only TAF (r = 0.837) closely correlated with RFM in all the 6 SEMSs, and ODF (r = 0.952), HF (r = 0.943) and TAF (r =0.906) closely correlated with RFM in 5 braided SEMSs. When the stent not fully expanded state (CODS was 6 or 8 mm), there was no strong correlation between three variables of stent flare structure and RFM.

Conclusion: The RF plays an important role in anti-migration when the covered SEMS not fully expanded state. In the fully expanded covered SEMS, the stent flare structure is strongly related to the anti-migration potential. The laser-cut stent potentially possesses extremely higher resistance force to migration whether the stent fully expands or not. The stent properties including radial force, flare structure and stent framework should be considered before selecting covered SEMS for biliary stricture.

Disclosure of Interest: None declared

P0249 EFFICIENCY AND SAFETY IN CASE OF TECHNICAL SUCCESS OF EUS-GUIDED TRANSHEPATIC ANTEGRADE BILIARY DRAINAGE. REPORT OF A MONOCENTRIC STUDY

S. Godat¹, E. Bories¹, F. Caillol¹, C. Pesenti¹, J.-P. Ratone¹, C. De Cassan¹, M. Giovannini¹

¹Gastroenterology, Paoli-Calmettes, Marseille, France

Contact E-mail Address: tagodat@gmail.com

Introduction: EUS-guided biliary drainage like choledochoduodenostomy, hepaticogastrostomy, antegrade stenting and rendezvous are alternative procedures in case of obstructive jaundice and altered anatomy or failed endoscopic-retrograde-cholangiography (ERCP). Complications related to EUS-guided antegrade drainage (EUS-GAD) are still described as substantial in up to 10%. Combination of procedures is sometimes suggest to avoid adverse events like biliary leakage, even in case of primary successful EUS-GAD.

Aims & Methods: Aims of this study were to evaluate the efficiency and safety of EUS-GAD with transhepatic access in case of technical success. We retrospectively reviewed computer data collected between 2006 and 2015 of patients with malignant and non-malignant biliary obstructive lesions who underwent EUS-GAD in a single, tertiary care center.

Results: A total of 20 patients were included (9F/11M, mean age 68, range 40-90, mean ASA score 2). Obstructive jaundice was due in most case to a malignant disease (19/20 patients, 95%). Reasons for EUS-GAD was failed ERCP in 13/20 (65%), duodenal stenosis in 4/20 (20%), altered anatomy after surgical intervention in 3/20 (15%). Intrahepatic biliary duct puncture was done with a 19G EchoTip® Ultrasound Needle in 16/20 (80%), with an EchoTip® Ultrasound Access Needle in 7/20 (35%). The hepaticogastric tract was performed in 20/20 with a cystostoma 6 fr, without puncture site closure at the end of procedure. Stenosis dilatation was done in 3/20 (15%) and calibration with cystostoma 6 fr in 9/20 (45%). SEMS was transpapillary in 19/20 (95%) and non transpapillary in 1/20 (5%). Drainage was completed in intraoperative stage in 2/20 (10%), once by hepaticogastrostomy and once by percutaneous drainage of the right liver. Clinical success was 17/20 (85%). 1/20 (5%) patient presented a persistent obstructive infectious cholangitis treated by another SEMS via ERCP. 2/20 (10%) patients died of infectious complication and incomplete drainage in case of advanced cancerous disease. One of these 2 patients was treated by EUS-GAD and hepaticogastrostomy in same time. None patients developed bilioma or bile leakage. 2/20 patients were treated later by an endoscopic duodenal SEMS for a duodenal obstruction.

Conclusion: EUS-GAD by transhepatic way is clinical effective and a safety method to treat biliary obstructive disease, in case of technical success. Closure of the gastric puncture site is not mandatory if drainage is efficient. Complementary method for biliary decompression should be combined in case of incomplete drainage and not to prevent potential adverse events. Additional studies are needed to target the most appropriate patient’s characteristics to undergo this type of intervention.

Disclosure of Interest: None declared

P0250 EUS-GUIDED ANTEGRADE BILIARY STENTING FOR UNRESECTABLE MALIGNANT BILIARY OBSTRUCTION IN PATIENTS WITH SURGICALLY ALTERED ANATOMY: A SINGLE CENTER PROSPECTIVE PILOT STUDY

T. Iwashita¹, I. Yasuda², T. Mukai¹, K. Iwata¹, S. Doi², S. Uemura¹, M. Mabuchi², M. Okuno¹, M. Shimizu¹

¹First Department of Internal Medicine, Gifu University Hospital, Gifu, ²Department of Gastroenterology, Teikyo University Mizonokuchi Hospital, Kanagawa, Japan

Contact E-mail Address: takuji@w7.dion.ne.jp

Introduction: Therapeutic ERCP for malignant biliary obstruction (MBO) in patients with surgically altered anatomy (SAA) is challenging even with application of enteroscopies. Percutaneous transhepatic biliary (PTB) or surgical approach is common alternatives for failed enteroscopy-based ERCP, but is associated with considerable complications.

Aims & Methods: The aim of this study was to evaluate the feasibility and safety of EUS-antegrade biliary stenting (EUS-ABS) for MBO in patients with SAA in prospective cohort.

EUS-ABS for unresectable MBO was attempted in 20 patients with SAA between 8/2012 and 2/2015. EUS-ABS was performed as follows: The left intra-hepatic bile duct (IHBD) was initially punctured from the intestine followed by cholangiography and antegrade guidewire manipulation. ABS with uncovered metallic stent was performed. A naso-biliary drainage tube (NBD) was placed if necesssary.

Results: SAAs were gastrectomy with Roux-en-Y reconstruction in 18, BillrothII reconstruction in 1, and hepatectomy with biliary reconstruction in 1. Biliary puncture was successful in 95% of the patients (19/20). In the patient with failed biliary puncture, inadequate biliary dilation did not allow EUS-guided puncture. The guidewire placement and subsequent ABS were successful in 19. Therefore, the overall technical success rate was 95% (19/20). NBD was placed in 3 and was removed in a median of 7 days. A median procedure time was 37 min (22-80). Adverse events were recognized in 20% of the patients (4/20) and were fever-up in 1 and mild pancreatitis in 3.

Conclusion: EUS-ABS for MBO in patients with SAA is feasible and can be an option as a safe and effective alternative. Further studies are warranted.

Disclosure of Interest: None declared

MONDAY, OCTOBER 26, 2015   09:00-17:00

SURGERY I – HALL 7__________

P0251 LONG-TERM OUTCOMES OF LAPAROSCOPIC SLEEVE GASTRECTOMY AND EFFECTS ON GERD SYMPTOMS

A. Santonicola¹, L. Angrisani², A. Hasani², C. Ciacci¹, P. Iovino¹

¹Gastrointestinal Unit, Department of Medicine and Surgery, University of Salerno, Salerno, ²General and Endoscopic Surgery Unit, S. Giovanni Bosco Hospital, Naples, Italy

Contact E-mail Address: antonellasantonicola83@gmail.com

Introduction: Laparoscopic Sleeve Gastrectomy (LSG) is a bariatric procedure with documented efficacy at short and midterm follow-up but there are only few data at long term follow-up.

Aims & Methods

Aim: To evaluate the long-term results of LSG describing the effect on GERD symptoms.

Methods: 105 obese patients eligible for bariatric surgery underwent LSG. According to the preoperative BMI obese patients were divided in two Groups: Group 1 (N=61, patients with preoperative BMI ≤ 50 Kg/m²) and Group 2 (N=44, patients with preoperative BMI > 50 Kg/m²). All underwent a preoperative assessment including evaluation of comorbidities, standardized GERD questionnaire, a double-contrast barium swallow, an upper-gastrointestinal endoscopy. At 5 years after LSG the following data were collected: BMI, GERD symptoms, modification of comorbidities, complications. The adopted criteria of surgical success were BMI ≤ 35 kg/m²in patients of Group 1 and BMI ≤ 40 kg/m²in patients of Group 2.

Results: Table 1 showed the demographic characteristics and prevalence of some comorbidities in the two groups of the study before LSG

	Group 1 N=61/105 (58.1%)	Group 2 N=44/105 (41.9%)	p
Weight, kg	114.2 ± 19.0	161.70 ± 19.76	<0.001
BMI, kg/m2	41.2 ± 4.7	57.25 ± 5.60	<0.001
Age, yr	39.9 ± 10.1	38.5 ± 11.5	0.51
Women, n (%)	44 (72,1)	23 (52,3)	0.04
Hypertension	19 (31.1%)	14 (31.8%)	0.88
Hyperlipidemia	20 (32.8%)	22 (50%)	0.11
Type 2 diabetes	11(18%)	9 (20%)	0.9
Typical GERD symptoms	19 (31%)	11 (25%)	0.6

At 5 years of follow-up, the success rate (BMI < 35) was achieved in 85.5% of Group 1 and in 62.9% of Group 2 (p=0.01). Among the patients of Group 1: 73.3% referred the resolution, 26.7% the persistence and 15% the new onset of GERD complaints. Among the patients of Group 2, 44.4% referred the resolution, 55.6% the persistence and 7.7% the new onset of GERD complaints. Patients of Group 1 that did not meet the criteria of surgical success (BMI < 35) at 5 years of follow-up showed a similar prevalence of postoperative GERD symptoms compared to patients who showed a surgical success according to the adopted success criteria (p=0.52). On the other hand, the patients of Group 2 that did not meet the criteria of surgical success (BMI < 40) at follow-up reported an higher prevalence of GERD symptoms (p=0.03).

Conclusion: LSG is an effective treatment and showed good weight loss outcome and resolution of comorbidities also on long term follow-up; although the success rate was significantly lower in pazients with preoperative BMI >50. A good percentage of patients with resolution of GERD symptoms was observed. However in patients with preoperative BMI >50 who failed to reach the success criteria, there was a high percentage of GERD persistence or new onset.

Disclosure of Interest: None declared

P0252 CLINICOPATHOLOGIC PROFILES AND CLINICAL OUTCOMES OF RECURRENCE AND MORTALITY OF PATIENTS WITH GASTROINTESTINAL STROMAL TUMORS AT THE PHILIPPINE GENERAL HOSPITAL

A. Q. Taguba¹, J. M. L. Balbuena², G. C. O. Floro³, E. I. Q. Villanueva⁴, M. A. A. De Lusong¹

¹Department of Medicine, Section of Gastroenterology, ²Department of Medicine, Section of Medical Oncology, ³Department of Medicine, ⁴Department of Laboratories, University of the Philippines - Philippine General Hospital, Manila, Philippines

Contact E-mail Address: aubreytaguba@gmail.com

Introduction: Gastrointestinal stromal tumors (GIST) occur in less than 1% of all digestive tumors, but are the most common mesenchymal neoplasms of the gastrointestinal tract. This is the first study that described the clinicopathologic profiles and clinical outcomes of recurrence and mortality of GIST patients at the Philippine General Hospital (PGH).

Aims & Methods: This was a retrospective, descriptive study including all biopsy-proven GIST cases in PGH from 2009 to 2014. Data from the review of hospital records were encoded and analyzed using Microsoft Excel.

Results: A total of 58 patients were included. Median age at diagnosis was 50 years, with female to male ratio of 1.3. Most common primary site was stomach (39.7%). Median duration of symptoms prior to first consult was 6 months. Most common presenting symptom was abdominal pain (37.9%). Mean size of primary tumor was 7.6 cm. Immunohistochemical staining result for CD 117 was positive in 63.8%. Five percent was noted to have unresectable metastatic disease at presentation. Liver was the site of metastasis for all these cases. Ninety- five percent underwent surgery and 100% of which was reported to have R0 resection. Majority were stratified as low risk (46.6%), followed by high risk (43.1%), then moderate risk (8.6%). After a median follow up of 32.5 months, 7.3% developed local recurrence and 5.1% was reported as mortality.

Conclusion: This hospital-based study showed that the clinicopathologic profile of GIST in PGH is comparable to other population-based studies. Survival was favorable in completely resected cases and in lower-risk groups.

Disclosure of Interest: None declared

P0253 NON-EXPOSURE ENDOSCOPIC FULL-THICKNESS RESECTION WITH SIMPLE SUTURE TECHNIQUE, A PRELIMINARY RANDOMIZED COMPARATIVE ANIMAL STUDY

C. G. Kim¹, H. M. Yoon¹, J. Y. Lee¹, S.-J. Cho¹, B. W. Eom¹, K. W. Ryu¹, Y.-W. Kim¹, I.J. Choi¹

¹Center for Gastric Cancer, National Cancer Center, Goyang-si, Republic of Korea

Contact E-mail Address: glse@ncc.re.kr

Introduction: Recently, endoscopic full-thickness resection (EFTR) with simple suture technique which did not expose gastric mucosa to peritoneum was developed. This new technique includes the steps of laparoscopic seromuscular suturing with a barbed suture thread (V-Loc), which results in inversion of the stomach wall; EFTR of the inverted stomach wall from inside the stomach; and finally, endoscopic mucosal suturing with endoloops and clips.

Aims & Methods: The aim of this study was to assess the outcome of EFTR using simple suture technique compared with that of laparoscopic wedge resection using linear stapler in animal model.

Preliminary analysis of prospective, randomized, controlled animal study. EFTR group (n=4) use the method of EFTR with simple suture technique and linear stapler group (n=4) use laparoscopic linear stapler for resection and suturing. Locations were cardia, upper body anterior side, upper body greater curvature, and antrum lessor curvature side of stomach. Successful complete resection (en-bloc resection with clear resection margin) rates and successful closure rates and complications of each group were evaluated.

Results: Complete resections rates were 100% of EFTR group and 50% of linear stapler group. Successful closure rates were 100% in both groups. Complications were developed in only linear stapler group (a leakage at cardia and a stenosis at antrum). The procedure time were significantly shorter in linear stapler group (mean ± SD; 29.5 ± 12.7 min) than EFTR group (112.3 ± 27.4 min, p=0.002). The sizes of resected tissue were significantly larger in linear stapler group (mean ± SD; 7.4 ± 0.9 cm) than EFTR group (4.6 ± 0.7 cm, p=0.002).

Conclusion: Outcome of non-exposure EFTR with simple suture technique was compatible with that of laparoscopic wedge resection using linear stapler in preliminary study. Completion of study is needed.

Disclosure of Interest: None declared

P0254 RISK FACTORS FOR MARGINAL ULCER AFTER GASTRIC BYPASS SURGERY FOR OBESITY

E. Sverdén ^1,2, F. Mattson², A. Sondén¹, T. Leinsköld¹, W. Tao², Y. Lu^2,3, J. Lagergren^2,4

¹Department of Upper Gastrointestinal Surgery, South Hospital, ²Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden, ³Department of Epidemiology and Biostatistics, Imperial College, ⁴Division of Cancer Studies, Kings College, London, United Kingdom

Contact E-mail Address: emma.sverden@sodersjukhuset.se

Introduction: Marginal ulcer (MU) is a common and potentially serious complication of gastric bypass surgery (GBP) for obesity, but little is known about its etiology.

Aims & Methods: The study aimed to asses risk factors for MU. This population-based cohort study of GBP in Sweden in 2006-2011 evaluated MU in relation to exposure to diabetes, hyperlipidemia, hypertension, chronic obstructive pulmonary disease (COPD), ulcer history, and use of proton pump inhibitors (PPIs), aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), and selective serotonin re-uptake inhibitors (SSRIs). Multivariable Cox proportional hazard regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for confounding.

Results: Among 20,294 GBP patients 2006-2011, diabetes and peptic ulcer history entailed statistically significantly increased risk of MU (HR=1.26, 95%CI 1.03-1.55 and HR=2.70, 95%CI 1.81-4.03), while hyperlipidemia, hypertension and COPD did not. PPI users had an increased HR of MU (HR=1.37, 95%CI 1.17-1.60). Aspirin and NSAID consumption ≤median entailed decreased HRs of MU (HR=0.56, 95%CI 0.37-0.86 and HR=0.30, 95%CI 0.24-0.38), while aspirin and NSAID users >median had an increased risk and no association with MU, respectively (HR=1.90, 95%CI 1.41-2.58 and HR=0.90, 95%CI 0.76-1.87). SSRI use ≤median had a decreased risk of MU (HR=0.50, 95%CI 0.37-0.67), while use >median entailed increased HR (HR=1.26, 95%CI 1.01-1.56).

Conclusion: Diabetes and peptic ulcer history seem to be risk factors for MU, but not hyperlipidemia, hypertension, or COPD. Limited doses of aspirin, NSAIDs and SSRIs might not increase the risk of MU, while higher doses of aspirin do. The association with PPI could be due to confounding by indication.

Disclosure of Interest: None declared

P0255 PREDICTING DIETARY INTAKE AFTER DISCHARGE FOLLOWING UPPER GASTROINTESTINAL SURGERY USING DIET DIARIES AND A GASTRIC ACCOMMODATION TEST PRIOR TO HOSPITAL DISCHARGE

F. Froghi¹, G. Sanders¹, T. Wheatley¹, R. Berrisford¹, P. Peyser¹, J. Rahamim¹, S. Lewis²

¹Upper GI Surgery, ²Gastroenterology, Derriford Hospital, Plymouth, Devon, UK, Plymouth, United Kingdom

Contact E-mail Address: farid.froghi@nhs.net

Introduction: Patients undergoing upper gastrointestinal surgery are often malnourished and following hospital discharge eat poorly despite dietetic input. The ‘slow satiety’ drinking test has been used to assess impaired gastric accommodation in functional dyspepsia. We examined if a drinking test done along with a 2 day diet diary could predict dietary intake post hospital discharge.

Aims & Methods: Prior to discharge, patients undergoing an oesophagectomy or total gastrectomy for cancer completed a 2-day dietary diary and underwent a gastric accommodation test. The accommodation test comprised of drinking 20ml/min of polymeric sip feed until they felt comfortably full. After hospital discharge patients completed 2 day dietary diaries at 3, 6 and 12 weeks. The diaries were analysed using Dietplan 6 and tabulated. We calculated energy intake as absolute intake (Kcal) and % of calculated requirement (using the Harris-Benedict formula). The accommodation test (volume of feed taken and time taken) were correlated (pearsons) with energy intake at hospital discharge. The accommodation test results and energy intake at hospital discharge were also correlated with energy intake at 3, 6 and 12 weeks post discharge.

Results: 28 patients (22 men), median age 66 (IQ range 60, 74) were recruited, oesophagectomy=18 Gastrectomy 10.

There was no correlation between the accommodation test and actual energy intake or % of required energy intake at hospital discharge.

Accomodation test		Energy (Kcal) intake as % of calculated requirements
Volume (ml)	Time (min)	Discharge	3 weeks	6 weeks	12 weeks
106 (72, 140)	389 (244, 534)	66 (58, 74)	78 (69, 87)	79 (71, 88)	90 (77, 102)
Correlation coefficient			0.34	0.43	0.40
P value			0.078	0.023	0.034

Dietary energy intake (Kcal) at hospital discharge did not correlate with post discharge energy intake, but when expressed as a % of calculated requirements there was a correlation at 6 and 12 weeks. The volume of feed consumed and time taken to drink the sip feed for the accommodation test did not correlate with post discharge dietary intake.

Conclusion: Energy intake at hospital discharge was modest and increased slowly to reach 90% of requirements at 12weeks. There was only a weak correlation between dietary records done just prior to hospital discharge and those done at 6 and 12 weeks. There was no correlation between the gastric accommodation test and post discharge dietary intake. Neither the gastric accommodation test or 2 day dietary records done just before hospital discharge after upper gastrointestinal surgery predicted post discharge dietary intake.

Disclosure of Interest: None declared

P0256 DISTRIBUTION OF LYMPH NODE METASTASES IN OESOPHAGEAL ADENOCARCINOMA; A PROSPECTIVE COHORT STUDY

H. T. Künzli ^1,2, A.-S. van Rijswijk³, S. L. Meijer⁴, M. I. van Berge Henegouwen³, S. S. Gisbertz³

¹Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, ²Gastroenterology and Hepatology, ³Surgery, ⁴Pathology, Academic Medical Centre, Amsterdam, Netherlands

Contact E-mail Address: h.t.kunzli@amc.uva.nl

Introduction: The distribution of lymph node metastases in oesophageal adenocarcinoma is not well studied. LN status is an important prognostic factor in oesophageal carcinoma. Distribution of metastatic LN may be influenced by tumor location, invasion depth and neo-adjuvant chemoradiation therapy. For the extent of the radiation field, as well as the extent of the lymphadenectomy it is essential to elucidate the distribution pattern of lymph node metastases.

Aims & Methods: To describe the distribution pattern of lymph node metastases in oesophageal adenocarcinoma and to identify lymph node echelons with high risk of metastases, adjusted for primary tumor location.

Between April 2014 and April 2015, all patients with an oesophageal adenocarcinoma undergoing transthoracic oesophagectomy with a complete 2 field lymphadenectomy were reviewed. In all patients the lymph node stations according to the 7^th edition of the AJCC classification were excised and separately sent for histopathological examination. Patients were excluded if they were diagnosed with an oesophageal squamous cell carcinoma, or when a salvage resection was performed.

Results: 43 patients (36 male, mean age 64 years) were included. An adenocarcinoma of the distal oesophagus was diagnosed in 40 patients, while 3 patients were diagnosed with an adenocarcinoma of the mid-oesophagus. 84% of patients were neo-adjuvantly treated with chemoradiation. A median of 36 (IQR 27-44) lymph nodes were resected.

Lymph node metastases were found in 22/43 (51%) patients, of which 2 patients (9%) were not treated with neo-adjuvant chemoradiation therapy. A median of 3 (IQR 1-10) tumour-positive lymph nodes were found.

Lymph node metastases were observed most frequently in the paracardial lymph node stations (9/22 patients, 41%: right vs. left = 4 vs. 5 patients), in lymph nodes around the left gastric artery (7/22, 32%), and in station 2R (paratracheal: 6/22, 27%). Ten out of 22 patients (45%) diagnosed with lymph node metastases, had tumour-positive lymph nodes above and below the diaphragm.

Conclusion: Oesophageal adenocarcinoma frequently metastasizes to both the mediastinal and abdominal lymph node stations. Paracardial lymph nodes, in close proximity to the primary tumor, have the highest risk of lymph node metastases.

Disclosure of Interest: None declared

P0257 SURVIVAL AFTER OESOPHAGECTOMY FOR CANCER PRE- AND POST- COMPUTED TOMOGRAPHY- POSITRON EMISSION TOMOGRAPHY (CT-PET) INCEPTION

J. Wheat¹, P. Blake¹, A. Karran¹, D. Chan¹, K. Foley¹, A. Roberts¹, W. Lewis¹

¹University Hospital of Wales, Cardiff, United Kingdom

Contact E-mail Address: Wyn.Lewis4@wales.nhs.uk

Introduction: CT-PET is indicated and funded in the UK for staging potentially curable oesophageal cancers in order to identify those patients with occult distant metastases. It has become an integral component of the staging pathway. The aim of this study is to analyse the effect of CT-PET use on overall survival and assess the patterns of recurrence before and after CT-PET inception.

Aims & Methods: Consecutive 424 oesophagectomies performed for cancer [median age 62 (24-80) yr; 337 male; 360 Adeno, 64 Squamous cell carcinoma; 254 neoadjuvant therapy] were recorded in a prospectively-maintained database. 169 were performed after the routine use of CT-PET began. Primary outcome measure was overall survival based on intention to treat.

Results: Overall 5-year survival pre-CT-PET was 37%, post-CT-PET was 49% (Chi² 4.991, df 1, p < 0.025). On multivariable analysis, pT stage (HR 1.497 [95% CI 1.344-1.667], p< 0.001) and pre- or post- CT-PET (HR 0.509 [95% CI 0.352-0.735], p < 0.001) were independently associated with survival. There were 119 (46.7%) recurrences in pre-CT-PET patients: 24.4% local; 58.8% distant; 16.8% both. Post-CT-PET patients had 33 (19.5%) recurrences: 27.3% local; 57.6% distant; 15.1% both.

Conclusion: The use of staging CT-PET independently improves overall survival in patients undergoing oesophagectomy for oesophageal cancer, although the patterns of recurrence remain unchanged.

Disclosure of Interest: None declared

P0258 SENTINEL NODE MAPPING BY USING A FLUORESCENT DYE AND VISIBLE RAY DURING LAPAROSCOPIC GASTRECTOMY FOR EARLY GASTRIC CANCER: RESULTS OF A PROSPECTIVE CLINICAL STUDY IN A SINGLE INSTITUTE

S. W. Jung¹, J.-H. Kim², J. W. Choe¹, Y.-J. Jang³, C. M. Lee²

¹Gastroenterology, ²Gastroenterologic Surgery, Korea University Medical Center Ansan Hospital, Ansan City, ³Gastroenterologic Surgery, Korea University Medical Center Guro Hospital, Seoul, Republic of Korea

Contact E-mail Address: ppongttai@gmail.com

Introduction: Sentinel node is defined as the first draining lymph node from the primary tumor, and sentinel node navigation surgery (SNNS) is a procedure in which the extent of surgery will be planned according to the metastatic status of sentinel node. Recently, SNNS has been investigated to avoid unneccesary extensive lympg node dissection in surgery for early gastric cancer (EGC). Various dyes and detecting methods were evaluated to acquire the accuracy of detecting sentinel nodes in SNNS for EGC.

Aims & Methods: The aim of this study is to investigatethe safety and feasibility of sentinel node mapping with a fluorescent dye and visible rayin the patients with gastric cancer.

Nineteen patients with gastric cancer, in whom laparoscopic distal gastrectomy with standard lymphadenectomy, were enrolled in this study. Before lymphadenectomy, they underwent endoscopic peritumoral injection of Fluorescein solution. The sentinel basin was investigated through inspecting the laparoscopic fluorescent imaging under a blue ray (wave length of 440-490 nm) emitted from a LED curing light.The detection rateand lymph node status were analyzed in the enrolled patients. In addition, short-term clinical outcomes were also investigated.

Results: Sentinel nodes were detected in18of 19enrolled patients (94.7%). Metastatic lymph nodes were found in two enrolled cases. These lymph nodes belonged to sentinel basin of each patients. Meanwhile, a patient (5.3%) underwent postoperative complication that had little relation with the sentinel node mapping. In all enrolled cases, nomortality was recorded.

Conclusion: The sentinel node mapping with visible light fluorescence was safe and effective at visualization of sentinel node. In addition, this method is superior than other fluorescent imaging techniques in visualizing the concrete correlation of sentinel node and surrounded structures.

Disclosure of Interest: None declared

P0259 WHAT IS THE BEST PROCEDURE FOR T1 TUMORS OF ESOPHAGO-GASTRIC JUNCTION ?

K. Noma¹, Y. Shirakawa¹, Y. Tsukumo¹, Y. Katsura¹, N. Maeda¹, S. Tanabe¹, K. Sakurama¹, M. Nishizaki¹, S. Kagawa¹, T. Fujiwara¹

¹Gastroenterological Surgery, Okayama University Medical School, Okayama, Japan

Contact E-mail Address: knoma@md.okayama-u.ac.jp

Introduction: There is still no consensus of surgical strategy for early stage tumor at esophago-gastric junction (EGJ). It is urgent issues to establish which stations of lymph node (LN) should be resected and to discuss which reconstruction is adequate for such patients that postoperative QOL is considered for their promised long-term survival.

Aims & Methods: The aim of this study is firstly to analyze our experienced 36 cases of pT1 EGJ tumor clinicopathologically and discuss appropriate LN resection fields and adequate reconstruction. Second is to introduce our novel reconstruction after lower esophagectomy and proximal gastrectomy, which is hand-sewn valvuloplastic esophagogastrostomy using “double flap technique”.

This study included 36 patients with pT1 tumor from total 131 patients with EGJ tumors. LN stations are reviewed by Japanese classification of esophageal cancer 2nd English edition (1).

Results: A total of 36 patients, consisting of 28 with adenocarcinoma (AC), 6 with squamous cell carcinoma (SCC) and 2 with other subtypes were enrolled in the study. Location of tumors was E: 21, EG: 4, E=G: 2, GE: 4 and G: 5 patients. pT1b was noted in 27 patients and LN metastasis was observed in 13.9% (5/36). Lower mediastinal LN metastasis (#110) was observed in only 1 patient, who had sm3 tumor and 3cm of esophageal invasion (EI). Abdominal station (#1, #3) was observed in other 4 patients. Only 2 patients both of who were of subtypes tumors were died of the illness. One was a patient of malignant melanoma, who had 5 LNs metastasis in #1, #3 and was died of liver metastasis. The other was a patient of basaloid, who had vascular invasion without any LN metastasis and was died of liver metastasis and mediastinal recurrence after 48 months. 32 patients (88.9%) survived without any recurrence.

As consideration, pT1a was noted in 9 patients, suggesting the difficulty of preoperative accurate diagnosis. For tumors located mainly in G, LN dissection should be performed in stations conformed to the guideline of proximal gastrectomy (Japanese gastric cancer treatment guideline ver. 4), but for tumors located mainly in E #110 station should be resected in addition. With regard to prognosis, AC or SCC groups showed radical cure and will be expected long-term prognosis. For reconstruction, we have adopted the hand-sewn morphological and functional valvuloplastic esophagogastrostomy with “double flap technique” since 2011, which showed excellent clinical outcome without any medication for reflux esophagitis even when anastomosis was located in lower mediastinum. So far, as our department policy proximal gastrectomy with D1+ is standard and if EI is more than 2cm we performed intently #110 dissection in addition. Reconstruction is the “double flap technique” for first choice regardless of the anastomosis site.

Conclusion: In conclusion, in cT1 tumors it is important to set the appropriate LN dissection stations. In addition, since there is expectation of long-term prognosis, there also need to be considered suitable reconstruction for long-term postoperative QOL.

Disclosure of Interest: None declared

P0260 ENDOSCOPIC TREATMENT OF GASTRIC ANASTOMOTIC LEAKS AND FISTULAS SECONDARY TO BARIATRIC SURGERY: SINGLE-CENTER EXPERIENCE

A. Belaïd¹, N. Kouinche¹, Y. Hoebeke², F. Corbisier², P. Warzee¹

¹Gastroenterology Unit, ²Surgical Unit, Grand Hôpital de Charleroi, Charleroi, Belgium

Contact E-mail Address: belaidaimen@gmail.com

Introduction: One of most feared complications of modern bariatric surgery is gastric anastomotic leak (GL). First-line treatment of leaks is external drainage collection and antibiotics. Treatment of the GL used clips, tissucol, Self-Expanding Metal endoprothesis (SEMS) and later pigtails. Endpoint of treatment is absence of contrast agent leakage on RX or CT.

Aims & Methods: We reviewed retrospectively 1794 cases of bariatric surgery performed in our hospital between 2008 and 2015 (Sleeve gastrectomy and Roux-en-Y gastric bypass). 19 patients were referred to gastro-enterologists for GL. Following treatments were used: SEMS exclusively (n:12), SEMS plus pigtails (n:1), SEMS then pigtails (n:2),double pigtails (n:3), clip (n:1).

Results: In SEMS group, the fistulas disappeared in most patients (12/13, 92.7%). In one patient, endoclip needed to be placed after removing the stent.

In the pigtails group, all patients responded (4/4,100%) to treatment.

Median hospitalization stay was 3.5 weeks in the SEMS group (n:13, 0.6-7.1w) and 1.1w in the pigtail group (n: 5, 1.1-4.42w).

Nineteen prosthesis (Ultraflex 3, Endoflex 11, Taewoong Medical 4, Life Partners Megastent (Barthet) 1) were used. Two patients were lost for follow up.

Early migration occurred in 6/13 (46.1%) patients with SEMS. Longstanding nausea, vomiting, retrosternal pain and gastro oesophageal reflux occurred in more than half of patients with SEMS (8/13, 61.5%) vs none in the pigtail group (0/4).

Conclusion: SEMS are effective in treatment of GL. Tolerance is usually bad, especially after Sleeve gastrectomy. More recently, endoscopic placement of double pigtails was introduced for treatment of GL. Early results in selected patients are promising in terms of fistulas closure and tolerance. Further studies are required to confirm these preliminary results.

Disclosure of Interest: None declared

P0261 EVALUATION OF THE CLINICAL EFFICIENCY OF THE INTESTINAL BLOOD FLOW QUANTIFICATION BY USING INDOCYANINE GREEN (ICG) AS A NEAR-INFRARED FLUORESCENT IMAGING SYSTEM

D. Nakano¹, T. Yamaguchi¹, H. Matsumoto¹, K. Takahashi¹, Y. Nakayama¹, M. Amaki¹, S. Natsume¹

¹Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan

Contact E-mail Address: daisukenakano0624@gmail.com

Introduction: Anastomotic leakage (AL) is one of the frequent complications in colorectal surgery. Although a principal factor of AL is thought to be vascular compromise, there is currently no accepted method to assess blood flow. To prevent AL, surgeons had to rely on the color of the intestine and the pulse of the marginal artery.

Aims & Methods: The aim of this study was to evaluate the clinical efficiency of the intestinal blood flow quantification by using indocyanine green (ICG) as a near-infrared fluorescent imaging system (NIFI). From May 2013 to April 2015, we enrolled patients who underwent low anterior resection (LAR). After 1.0 ml of ICG solution (2.5mg/ml) was injected intravenously by the anesthetist just before formation of the anastomosis, the blood flow was visualized in real time by NIFI.

Results: The median (range) age of the patients was 70 (38-81) years. The median (range) BMI was 23.7 (15.4-30.6) kg/m². Forty-six percent of patients were female. In all cases, the evaluation of the blood flow distribution of intestinal wall was clearly achieved. After ICG injection, median (range) time to visualize the blood flow was 35 (22-105) seconds. The occurrence of delay in the blood flow distribution to the anastomotic site compared to the proximal side of intestine was observed in 3 cases. In 2 of the 3 cases, revision of the intestinal transection point was done before formation of the anastomosis. In the other 1 case, AL due to bowel ischemia occurred.

Conclusion: The intestinal blood flow can be evaluated by ICG fluorescence by NIFI. The occurrence of delay in the blood flow distribution may cause AL due to ischemia. By using ICG fluorescence, intestinal ischemia of the anastomotic site of LAR might be avoided.

Disclosure of Interest: None declared

P0262 PASIREOTIDE IN DUMPING SYNDROME – RESULTS FROM A PHASE 2, INTERNATIONAL, MULTICENTRE STUDY

J. Tack¹, J. Arts², J. Aberle³, J. C. LaRocque⁴, V. Q. Passos⁵, P. O’Connell⁶, A. P. van Beek⁷

¹University Hospital Gasthuisberg, Leuven, Belgium, ²AZ Sint Lucas, Brugge, Belgium, ³Universitaetsklinikum Hamburg-Eppendorf, Hamburg, Germany, ⁴Virginia Endocrinology Research, Chesapeake, VA, United States, ⁵Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States, ⁶Novartis Pharma AG, Basel, Switzerland, ⁷University of Groningen, University Medical Center Groningen, Groningen, Netherlands

Contact E-mail Address: a.p.van.beek@umcg.nl

Introduction: Dumping syndrome is a prevalent complication of gastric bypass surgery, characterised by early (cardiovascular and gastrointestinal response, along with rise in haematocrit [Ht] and pulse rate [PR]) and late (hypoglycaemia due to excess insulin) postprandial symptoms. Only a subset of patients (pts) responds to treatment based on dietary measures, off-label use of acarbose and somatostatin analogues (SSA). Pasireotide (PAS), a next-generation SSA with high affinity to 4 of the 5 somatostatin receptor subtypes (sst), being a potent inhibitor of incretin and insulin secretion (via sst₂ and sst₅), prevents postprandial hypoglycaemia.

Aims & Methods: This is a single-arm, open-label, multicentre, intra-patient dose escalation, phase 2 study to evaluate the preliminary efficacy, safety and pharmacokinetics of PAS subcutaneous (s.c.) and long-acting release (LAR) in pts with dumping syndrome. The 6-month (mo) core period included a 3-mo s.c. phase followed by a 3-mo LAR phase. Eligible pts started treatment with PAS s.c. 50μg tid (before meals); dose could be increased by increment of 50μg up to 200μg tid based on the presence of hypoglycaemia (plasma glucose <60mg/dL) during an oral glucose tolerance test (OGTT) in the s.c. phase. In the LAR phase, pts received a fixed dose of PAS LAR 10 or 20mg based on the dose at the end of s.c. phase. Primary endpoint was the proportion of pts with no hypoglycaemia during an OGTT (ie, response rate [RR]) at the end of s.c. phase (mo 3). A RR of ≥50% was considered to be clinically relevant. Secondary endpoints included RR at the end of LAR phase (mo 6). The Ht levels and PR were evaluated at all OGTT time points.

Results: Of the 43 pts enrolled, 33 and 31 pts completed the s.c. and LAR phase, respectively. Main reason for discontinuation was adverse events (AEs; 11.6% [n=5]). The RR in terms of prevention of hypoglycaemia was 60.5% (26/43; 95% CI: 44.4%>75.0%) and 36.4% (12/33; 95% CI: 20.4%>54.9%) in the s.c. and LAR phases, respectively. Notably, plasma glucose levels during OGTT were higher at all time points with s.c. dose vs baseline and vs LAR dose. Fewer pts had an increase in PR of ≥10 beat/min and an increase in Ht level of ≥3% (from pre-OGTT to 30 min post-OGTT) at mo 3 than at the baseline (18.6% vs 60.5% and 16.3% vs 27.9%, respectively). Overall, the most frequent (>15% of pts [N=43]) AEs were headache (32.6%); diarrhoea, hypoglycaemia (25.6% each); abdominal pain (18.6%); upper abdominal pain and nausea (16.3% each). Grade 3/4 AEs occurred in 32.6% pts; most frequent (≥2 pts) were hypoglycaemia (9.3%); diarrhoea, upper abdominal pain, dizziness and small intestinal obstruction (4.7% each).

Conclusion: These results suggest that PAS s.c. effectively controls postprandial hypoglycaemia and improves changes in PR and Ht in pts with dumping syndrome. PAS s.c. and LAR were well tolerated; no new safety signals were identified in this population. A phase 3 study is warranted to confirm the effects of PAS in dumping syndrome.

Disclosure of Interest: J. Tack Financial support for research: Novartis, Shire, Zeria, Consultancy: AlfaWassermann, Almirall, AstraZeneca, Danone, GI Dynamics, GlaxoSmithKline, Ironwood, Janssen, Menarini, Novartis, Rhythm, Shire, Sucampo, Takeda, Theravance, Tsumura, Yuhan, Zeria, Conflict with: Abbott, Almirall, AstraZeneca, Janssen, Menarini, Novartis, Shire, Takeda, Zeria as Speakers' Bureau, J. Arts: None declared, J. Aberle: None declared, J. LaRocque Financial support for research: Novartis, V. Passos Shareholder: Novartis Pharmaceutical, Conflict with: Novartis Pharmaceutical as an employee, P. O’Connell Conflict with: Novartis Pharma AG as an employee, A. van Beek Financial support for research: Novartis

P0263 TRICLOSAN-COATED SUTURES FOR PREVENTION OF SURGICAL SITE INFECTION AFTER COLORECTAL CANCER SURGERY: A PROPENSITY SCORE-MATCHED RETROSPECTIVE STUDY

K. Yamashita¹, S. Takeno¹, S. Hoshino¹, H. shiwaku¹, N. Aisu¹, Y. Yoshida¹, S. Tanimura¹, T. Hashimoto¹, T. Sasaki¹, Y. Yamauchi¹, T. Noritomi¹, Y. Yamashita¹

¹Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan

Contact E-mail Address: kanefumi0519@yahoo.co.jp

Introduction: Colorectal surgery continues to have the highest rate of surgical site infections (SSIs) of all surgical procedures, accounting for 5–45% of all SSIs. Triclosan-coated sutures were developed to prevent bacterial colonisation of the suture material, and consequently to impair the local mechanisms of wound decontamination. We aimed to assess the effectiveness of triclosan-coated sutures used for skin closure on the rate of SSIs in colorectal cancer surgery.

Aims & Methods: We aimed to assess the effectiveness of triclosan-coated sutures used for skin closure on the rate of SSIs in colorectal cancer surgery.

Until August 2012, our centre (Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine) used conventional methods for skin closure in colorectal cancer surgery. We were therefore able to retrospectively collect surveillance data from a 1.5 year period, which formed the control group. From September 2012, we began to use triclosan-coated polydioxanone antimicrobial sutures (PDS plus) for skin closure. We collected data for the study group from September 2012 until August 2013. Using propensity score matching, the control and study group cases were matched based on the following variables: patient age, sex, body mass index (BMI), medication use, complications, lifestyle-related factors, American Society of Anesthesiologists (ASA) physical status score as determined by an anaesthesiologist, type of surgery, operation time, quantity of blood lost, quantity of blood transfused, surgical wound classification, and method of skin closure. The baseline differences and selection bias were adjusted using the propensity score-matching method.

Results: A total of 374 colorectal cancer surgery patients were included in this study (control group, 221 patients; study group, 153 patients). Of all cases, 76 pairs were matched using the propensity score-matching method. Baseline patient characteristics were similar in the propensity score-matched groups. The incidence of SSIs within 30 days of the index operation, before matching, was 14.0% (31/221) in the control group and 7.2% (11/153) in the study group; the difference was statistically significant (p=0.030). After matching, the incidence of SSIs was 23.7% (18/76) in the control group and 5.3% (4/76) in the study group; the difference was statistically significant (p=0.001). Multivariable logistic regression analysis revealed that type of surgery was an independent factor affecting the incidence of SSIs prior to propensity score matching (p=0.032). Emergent surgery (p=0.017) and PDS plus (p=0.002) were independent factors affecting the incidence of SSIs following propensity score matching.

Conclusion: Use of triclosan-coated sutures was associated with a significant decrease in the risk of SSIs following colorectal surgery.

Disclosure of Interest: None declared

P0264 THE IMPORTANCE OF BEING HONEST. METICULOUS REGISTRATION OF FOLLOW-UP DATA IN QUALITY REGISTERS INCREASE DATA VALIDITY - A STUDY OF 94185 CHOLECYSTECTOMIES

L. Enochsson ^1,2, A. Wallin³, J. Österberg³

¹Center for Digestive Diseases, Karolinska University Hospital, ²CLINTEC, Karolinska Institutet, Stockholm, ³Department of Surgery, Mora Hospital, Mora, Sweden

Contact E-mail Address: lars.enochsson@ki.se

Introduction: The Swedish national registry of gallstone surgery and endoscopic retrograde cholangiopancreatography, GallRiks, was founded in May 2005 and by the end of 2014 includes 98677 cholecystectomy registrations. The cholecystectomies are registered online by the surgeons immediately after surgery and then there is a 30-day postoperative follow-up (1). However, the hospitals participating in GallRiks have different complete 30-day follow-up frequencies.

Aims & Methods

Aim: The aim of our study was to analyze if these differences affect the frequency of reported adverse events.

Methods: 98677 cholecystectomy registrations were included. A total of 4492 registrations were excluded due to being non-index procedures, the cholecystectomy being part of major surgery or registrations with missing data. A total of 94185 cholecystectomies were included in the analysis (2.8% with complete 30-day follow-up of ≤90 (Group A) and 97.2% with a complete 30-day follow-up of >90% (Group B).

Results: The frequency of complete 30-day follow-up (≤90%) has increased somewhat from 0.2% (2005) to 4.1% (2014). The patients in Group A were somewhat older, included more urgent operations and slightly more males. The reported 30-day postprocedural adverse event rate was significantly less in Group A (OR 0.82; 95% CI 0.75-0.89) as well as the pancreatitis rate (OR 0.55; 95% CI 0.38-0.78) (Table 1). However, the perforation rate was significantly higher (OR 2.29; 95% CI 1.55-3.30) compared to Group B.

	Adverse events
	≤90% 30d follow up vs. >90% 30d follow-up
	Univariate		Multivariate
	OR	95%CI	OR	95%CI
Intraprocedural	0.96	(0.85-1.09)	0.95	(0.84-1.07)
Postprocedural	0.86	(0.79-0.93)	0.82	(0.75-0.89)
Pancreatitis	0.58	(0.39-0.82)	0.55	(0.38-0.78)
Cholangitis	1.01	(0.54-1.73)	0.95	(0.51-1.62)
Bleeding	1.04	(0.81-1.32)	1	(0.78-1.27)
Perforation	2.28	(1.54-3.28)	2.29	(1.55-3.30)
Infection	1.09	(0.91-1.30)	1.04	(0.87-1.24)

Conclusion: The lower frequency of postoperative adverse events and pancreatitis in Group A could indicate that a lower frequency of 30-day follow-up registrations risk to miss cholecystectomies with adverse events whereas serious complications like perforation of the gut are seldom missed. The importance of a meticulous registration in quality registers in order to get valid data cannot be overstated.

Disclosure of Interest: None declared

P0265 LONG-TERM FUNCTIONAL OUTCOME AND QUALITY OF LIFE AFTER RESTORATIVE PROCTOCOLECTOMY AND ILEAL - POUCH ANAL ANASTOMOSIS IN ULCERATIVE COLITIS PATIENTS

M. Kostrejova¹, D. Duricova², M. Lukas², P. Pekny¹, M. Bortlik², J. Dosedel¹, A. Fialova³, R. Sequens⁴

¹Department of Gastroenterology, Hospital of Merciful Sisters of St.Charles Borromeo, ²IBD Clinical and Research Centre ISCARE, ISCARE A.S. Charles University in Prague, ³The National Institute of Public Health, The National of Institute of Public Health, ⁴NH - Hospital a.s. Horovice, Department of Surgery, Prague, Czech Republic

Contact E-mail Address: martakostrejova@seznam.cz

Introduction: Restorative proctocolectomy with ileal-pouch anal anastomosis (IPAA) has become the surgical procedure of choice in patients with UC.

Aims & Methods: The aim of the study was to assess the long-term functional results and quality of life in those UC (n=138) patients, who underwent IPAA from 1993-2013 in two Czech referral centers. In 129 of patients had been perfomed three-stage procedure, using stapled anastomosis. Qualite of life (QoL) was evaluated by using the Medical Outcome 36 item Health Survey, and Wexner Continence Grading Scale.The outcome of SF-36 item questionnaire has been compared with the Oxford study for the European. Statistical significance in all tests set to p,0.05, a Cronbach´s alpha reliability of psychometrics tests was from 0.737-0.917.

Results: A total of 114 out of 119 pts completely answered the questionnaires. 62% of whom were male, a median of age (interquartile range) at proctocolectomy was 34 (27-44) years. During a median (range) follow-up of 7.9 (2.1–20.7) years. In 28% of these patients developed septic and/or obstructive and perianal complications. In 8.7% resp. 10.2% of patients anastomotic stricturae and complete fistula have been detected. Pouch failure occured in 7.9% of the patients and in 5.5% of pts “ re-do” puche was done and in 2 pts continent ileostomy was done. One female patient developed carcinoma in IPAA seventeen months after poctocolectomy.

24% of pts developed at least one episode acute pouchitis, 15.0% had recurrent pouchitis. In majority of patients (63%) the median of functional outcome was 2 (0-4), according to the Wexner continence score. The median range of bowel moments was 5 (1-8) during the day, and 1 (0-3) at night. 24% had episodes of soiling, 11% urgency defecation, in 2/1.7% was seen true faecal incontinence. Nevertheless, 50% of patients occasionally had to change daily activities, and up to 62% of patients were taking antidiarrheal medications.

In patients after IPAA were observed slightly but significantly lower mean of QoL overall, and in five of eight SF-36 health dimensions than general population.The HRQoL was mainly impaired in the psychological and social areas and to a lesser degree in physical area. Physical Component Summary (PCS) and Mental Component Summary (MCS) were 46.37 and 46.55 (both are 50 in general population), respectively (p < 0.001). Patients with a certain degree of defecation function damage with a median Wexner score 9 (6-17) had a significantly lower quality of life in majority of dimensions of SF-36 than patients with perfect continence (p< 0.001). Regarding pouchitis in female significantly was affected all dimensions of MCS (median score 37, p< 0.028). On the other hand pts with perfect continence had normal QoL in all dimensions.

Conclusion: The ileal – pouch anal anastomosis in patients with ulcerative colitis confers a good quality of life. The majority of patients are fully continent. Subjective assessment of QoL and overall satisfaction was very high (98.3%).

Disclosure of Interest: None declared

P0266 RESULTS OF ENDOSCOPIC DILATION OF ESOPHAGOGASTRIC ANASTOMOTIC STENOSIS

M. C. Franco¹, B. D. C. Martins¹, J. T. Rios¹, V. D. S. Medeiros¹, F. A. Retes¹, R. S. Uemura¹, F. S. Kawaguti¹, M. S. Lima¹, C. M. P. S. Pennacchi¹, C. C. Gusmon¹, S. N. Geiger¹, E. R. Baba¹, A. V. Safatle-Ribeiro¹, S. E. Matuguma¹, U. Ribeiro Jr¹, F. Maluf-Filho¹

¹São Paulo Cancer Institute, São Paulo, Brazil

Contact E-mail Address: mcavalcantefranco@gmail.com

Introduction: Esophagogastric anastomotic stenosis is the most common cause of dysphagia after esophagectomy with esophagogastroplasty for esophageal cancer.

Aims & Methods: To evaluate the results of endoscopic dilation therapy for esophagogastric anastomotic stenosis.

Retrospective analysis of prospectively collected database of patients who underwent subtotal esophagectomy for cancer and developed dysphagia due stenosis of the esophagogastric anastomosis, at the Cancer Institute of the University of São Paulo.

Results: From May 2010 to May 2014, a total of 32 patients were included, with dysphagia and stenosis of the esophagogastric anastomosis, and a median of 3 months after surgery (ranging from 0.5 to 19 months). Mean age was 58 years (range: 40 – 72 years), with male predominance (78.1%). Eight (25%) patients had fistulas or anastomotic leakage in the postoperative period. A 9.8mm endoscope could not traverse the stricture in 18 cases (56%). For endoscopic dilation, guidewire-assisted bougies (Savary-Gilliard; Wilson-Cook Medical) were used in 17 cases (56%), guidewire-assisted bougies or hydrostatic balloons (CRE-TTS, Boston Scientific) in 14 cases (43%), and hydrostatic balloons alone in 1 case. The maximum diameter of 16 mm was achieved in 31 patients (96%), with a median of 5 sessions per patient (range: 1 – 25 sessions per patient). There were no major complications, such as perforation or massive bleeding. Triamcinolone injections were performed in 22 cases (69%), with a mean of 2.1 sessions per patient (range: 1 – 5 sessions per patient), removal of sutures in 7 (22%), incisional therapy using electrocautery in 2 (6%), and placement of self-expanding metallic stent in 1 case. Therapeutic success rate, defined as clinical improvement without further dilation for a period of at least 6 months, was obtained in 28 patients (87.5%).

Conclusion: When patients undergoing esophagectomy and esophagogastric anastomosis develop symptomatic stenosis, they usually present dysphagia in the first 3 months after the operation. The endoscopic dilation carried out with bougies or balloons, associated with corticosteroid injection, is successful in almost 90% of the patients with no life-threatening related complications.

Disclosure of Interest: None declared

P0267 RISK OF NEW-ONSET DIABETES AFTER PANCREATODUODENECTOMY: A SYSTEMATIC REVIEW

S. Haijtink¹, T. Mungroop¹, W. Eshuis¹, Y. Issa¹, L. van Rijssen¹, C. van Eijck², J. DeVries³, O. Busch¹, M. Besselink¹

¹Department of Surgery, Academic Medical Center Amsterdam, Amsterdam, ²Department of Surgery, Erasmus Medical Center, Rotterdam, ³Department of Endocrinology, Academic Medical Center Amsterdam, Amsterdam, Netherlands

Contact E-mail Address: s.a.l.haijtink@amc.uva.nl

Introduction: Resection is the only curative treatment option for patients with pancreatic and periampullary cancer. After pancreatoduodenectomy (PD) patients are at risk of developing new-onset diabetes mellitus (NODM). The exact risk of NODM after PD is relevant when counseling patients, but it is currently unknown since systematic reviews are lacking. The aim of this study is to determine the risk of new-onset diabetes mellitus (NODM) after pancreatoduodenectomy (PD) performed for benign and malignant diseases.

Aims & Methods: A systematic literature search was performed up to October 1^st 2014 in PubMed, Embase (Ovid) and the Cochrane Library in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All studies reporting on the incidence of NODM following PD for benign or (pre)malignant pancreatic or periampullary tumors were included. Studies of patients undergoing PD for chronic pancreatitis were excluded. Primary outcome was incidence of NODM.

Results: Of the 1863 studies identified, 13 studies (715 patients) fulfilled the eligibility criteria. Patients underwent PD for cancer (n=602), benign disease (n=62), or neoplasm from unclear origin (n=51). The weighted mean percentage of NODM was 11.6% (±11.2). Only 4 studies, comprising 34 patients with NODM, reported the incidence of insulin-dependent diabetes mellitus (IDDM). The weighted mean post-PD percentage of IDDM among these patients with NODM was 20.5% (±6.02).

Conclusion: Incidence of NODM following PD for pancreatic or periampullary tumors is 11.6%. Routine postoperative screening for NODM seems advisable. More research into the risk of IDDM following PD is needed.

Disclosure of Interest: None declared

P0268 PERITONEAL IRRIGATION DOES NOT REDUCE RATE OF POST-OPERATIVE FORMATION OF INTRA-ABDOMINAL ABSCESS AFTER PERFORATED APPENDECTOMY

S. Groen¹, L. de Nes², H. Barton¹, S. Donkervoort¹, S. Festen¹, on behalf of Dirty Belly Working Group

¹Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam/Netherlands, Amsterdam, Netherlands, ²Surgery, Humanitas Research Hospital, Milano, Italy

Contact E-mail Address: syl.groen@gmail.com

Introduction: Annually 16,000 appendectomies are performed in the Netherlands. Although the overall rate of post-operative intra-abdominal abscess (PIAA) formation is small, there is a potential significant effect on mortality, morbidity, duration of hospital-admission and costs. Largest risk in developing PIAA is after perforated appendicitis (20%). Peritoneal-irrigation during surgery is frequently used as preventive procedure, however literature is lacking supporting evidence. The only available prospective study describes an increase of abscess-formation in a pediatric study-group. Primary objective of our study was to determine the efficacy of peritoneal-irrigation in perforated appendicitis on PIAA in adults.

Aims & Methods: All patients undergoing appendectomy for acute appendicitis from January, 2008, until December, 2013, were included in a database. Exclusion-criteria were age < 18yrs, incidental and interval-appendectomy. PIAA is used as primary outcome measure.

Results: 1163 of 1467 appendectomies were included. PIAA was diagnosed in 61 patients (5.2%). There were 245 (22.1%) appendix-perforations during surgery in which 37 patients (15.1%) developed PIAA, versus 24 of 917 patients in the non-irrigation group (2.6%). Between the peritoneal-irrigation and non-irrigation group were no significant differences in patient-characteristics. In the irrigation-group a greater risk in developing PIAA is shown versus non-irrigation (18.6% vs. 6.8%, OR 3.6, BI 0.9–13, p=0.082). Additionally, irrigation is associated with a longer hospital-admission, on an average of 1.7 days (OR 1.1, BI 1.0-1.4, P=0.004).

Conclusion: Peritoneal-Irrigation during surgery in perforated appendicitis does not significantly reduce the rate PIAA formation in this retrospective study and probably increases the rate of this complication. Furthermore, patients in the irrigation group were admitted significantly longer.

Disclosure of Interest: None declared

P0269 STAGE APPROACH TO MEDICAL MANAGEMENT OF INTRA-ABDOMINAL HYPERTENSION

V. Teplyi¹, I. Kolosovych¹, S. Tarasenko¹, A. Kolosovych¹

¹Surgery #2, O.O. Bogomolets National Medical University, Kyiv, Ukraine

Contact E-mail Address: teplyy@ukr.net

Introduction: Intra-abdominal hypertension (IAH) may lead to the development of abdominal compartment syndrome (ACS) – potentially lethal complication. The experts proposed IAH/ACS medical management algorithm which on our point of view is something general (1).

Aims & Methods: The purpose of this study was to detail the stage approach to the management of IAH/ACS in the patients with general surgical pathology. The monitoring of intra-abdominal pressure (IAP) was performed by trans-bladder technique. In 7 operated patients (group 1) the volume of abdominal cavity was decreased by the abdominal wall surgery (5 – abdominoplasty, 2 – ventral hernioplasty). In 25 other patients (group 2) IAH was caused by the increase of the volume of abdominal content (14 – acute pancreatitis, 5 – paralytic ileus secondary to diffuse purulent peritonitis and in 2 – because of uremia and 4 – cirrhosis with progressive ascites). Taking into account that the rise of IAP always is a result of the disproportion of the ratio of the abdominal content volume to the volume of the abdominal cavity, management was focused on the decrease of the former or enlargement of the latter one. The first stage measures in the group 1 were focused on the improving of the abdominal wall compliance. In all patients receiving mechanical ventilation we started from the adjustment of the ventilator settings (decrease of tidal volume and increase of the respiratory rate). In parallel the adequacy of sedation and analgesia were checked, constricting dressings and bandages were removed. The same management was hold at the 1 stage in all patients of the group 2 on mechanical ventilation. But the main efforts were directed to reduce the volume of abdominal content. Thus in 8 non-operated patients of the group 2 with severe abdominal accumulations primary stage included their percutaneous drainage under ultrasound control. The main cause of the increase of the abdominal content volume in 15 patients was paralytic ileus. Here the first stage was focused on the evacuation of the gastro-intestinal content. If it was not effective, on the second stage enteral nutrition was minimized or even discontinued and fluid administration was optimized. The 3 stage treatment for these patients was neuromuscular blockade.

Results: The adjustment of the ventilator setting sand removing of compressive garments permitted to decrease IAP in 16 patients (including all patients of group 1) on 18.8 ± 2.6 mm H₂O. Thus there was no necessity to go to the next stage. But if abdominal wall compliance cannot be improved, neuromuscular blockade should be considered. Drainage of severe abdominal accumulations permitted to decrease IAP to less than 200 mm H₂O in 6 of 8 patients. In remaining 2 patients therapy was escalated to the second stage.

Conclusion: In 68.8% of cases it was enough the first stage measures to stabilize and decrease IAP. Described approach permitted to escape the decompressive laparostomy in 93.8% of patients without redundant manipulations.

Disclosure of Interest: None declared

MONDAY, OCTOBER 26, 2015   09:00-17:00

IBD I – HALL 7__________

P0271 RISK OF THROMBOEMBOLIC DISEASE IN INFLAMMATORY BOWEL DISEASE

A. Kumar¹, B. Disney¹, L. Wood¹, J. Slater¹, S. de Silva¹

¹Gastroenterology, Russells Hall Hospital, Birmingham, United Kingdom

Contact E-mail Address: aditikumar@nhs.net

Introduction: Patients with inflammatory bowel disease (IBD) are thought to be associated with an increased risk of developing venous thromboembolic (VTE) disease and arterial thombi (AT). There is conflicting data on the prevalence of VTE disease and AT in IBD, varying between 1.2% and 6.7% in clinical studies, which rises to 39% in postmortem studies. Our aims were to evaluate the rate and risk factors of VTE and AT in a large cohort of IBD patients.

Aims & Methods: We performed a retrospective review between the years 1984 to 2014 of all patients with IBD. These patients were identified from the IBD database and cross-referenced with the online electronic reporting system, patient notes and clinic letters.

Results: There were a total of 1678 patients with IBD, with 47 found to have VTE and AT, giving a prevalence rate of 2.8%. Of these 47 patients, 8 (17%) patients had recurrent disease with 6 (12.8%)patients having 2 incidents and 2 (4.2%) patients having 3 incidents of VTE disease. The median age was 60.2 years old with a greater risk for males than females (55% versus 45%) and with ulcerative colitis than Crohn’s disease (2.8% versus 0.87%). A total of 6 patients were inpatients, unrelated to their IBD, and a diagnosis of VTE/AT was confirmed within 5 days of admission.

36 (2.1%) patients were diagnosed with deep venous thrombosis (DVT) and 20 (1.2%) with pulmonary embolism (PE). The remaining four had portal vein thrombosis, common femoral artery occlusion, femoral artery embolus and superficial femoral artery occlusion. Three patients were diagnosed with both DVT and PE in the same admission. The average duration from time of IBD diagnosis to VTE confirmation was 7.4 years. 5 patients were identified with VTE prior to their IBD diagnosis.

At the time of their diagnosis, 3 (5.3%) patients were treated for malignancy in the previous six months and 4 (7%) had undergone surgery in the previous four weeks. 32 (56%) patients were being treated with 5-aminosalicylic acid (5ASA) drugs, 17 (30%) with azathioprine, 12 (21%) with oral steroids, 4 (7%) with intravenous (IV) steroids, 2 (4%) had infliximab and 1 (2%) had adalimumab. Blood tests at time of diagnosis showed a median CRP of 46 and platelet count of 345. The mortality rate was 10.6%, of which one death was directly related to their VTE. 10.5% underwent surgery, 63% were anticoagulated and 1.8% underwent failed tissue plasminogen activator (TPA) therapy. 3.5% were left with a disability secondary to their VTE disease.

Conclusion: Thromboembolic disease is an increasingly prevalent and preventable complication of IBD. Positive risk factors identified in our cohort were patients that were male, increasing age and diagnosis of ulcerative colitis. Considering almost one third of those diagnosed were receiving oral or IV steroid therapy and had an average raised CRP, this supports the view that a disease flare is an ongoing risk factor for developing VTE and AT.

Disclosure of Interest: None declared

P0272 ORAL ADMINISTRATION OF LACTOBACILLUS PLANTARUM 06CC2 ATTENUATES THE SEVERITY OF DEXTRAN SULFATE SODIUM-INDUCED COLITIS IN MICE

A. Tanaka¹, S. Kanmura¹, K. Kawabata¹, T. Fujita¹, S. Arima¹, F. Sasaki¹, Y. Nasu¹, S. Tanoue¹, S. Hashimoto¹, H. Taguchi¹, M. Numata², A. Ido¹

¹Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, ²Division of Endoscopy, Kagoshima University Hospital, Kagoshima, Japan

Contact E-mail Address: tanakaki@m3.kufm.kagoshima-u.ac.jp

Introduction: The dysbiosis of enteric microbiota cause host mucosal immune responses that result in gastrointestinal diseases such as enterocolitis.

Aims & Methods: In this study, we investigated the beneficial effect of Lactobacillus plantarum (LP) 06CC2 in dextran sulfate sodium (DSS)-induced colitis in C57BL6 mice. Heat-killed lyophilized LP 06CC2 was suspended in PBS. Two mice groups that had received DSS were orally administered PBS only (control group) or LP 06CC2 (LP group) by gavage for 15 consecutive days. We assessed the severity of colitis using a disease activity index, measured the colon length and weight, and colon tissue was examined macroscopically and histopathologically. We also collected colonic lamina propria mononuclear cells (LPMCs). The gene expressions of inflammatory cytokines (IFN-γ, IL-6, IL-12, TNF-α and IL-10) in LPMCs were determined.

Results: The body weight reduction in the LP group was significantly suppressed relative to the control group. The LP group demonstrated significantly lower disease activity index (1.5 ± 0.8 vs. 0.2 ± 0.3, respectively; p < 0.05) and pathology score (6.3 ± 1.5 vs. 3.8 ± 1.3, respectively; p < 0.05) compared to the control group. The LP strain significantly prevented foreshortening of the large intestine: the average colon length was 80 ± 8 mm in the LP group and 94 ± 7 mm in the control group (p < 0.01). IL-10 expression in colonic LPMCs was significantly higher in the LP group than the control group, although there was no significant difference of IFN-γ, IL-6, IL-12 expressions in LPMCs between two groups.

Conclusion: The LP 06CC2 strain attenuated colon inflammation by induction of IL-10 production in the colonic LPMCs.

Disclosure of Interest: None declared

P0273 ACTIVATION OF THE GCN2/EIF2ALPHA/ATF4 SIGNALING PATHWAY TRIGGERS AUTOPHAGY RESPONSE TO INFECTION WITH CROHN’S DISEASE-ASSOCIATED ADHERENT-INVASIVE ESCHERICHIA COLI

A. Bretin ^1,2, J. Carrière^1,2, G. Dalmasso^1,2, N. Barnich^1,2, A. Bergougnoux^1,2, W. B'Chir³, A.-C. Maurin³, A. Bruhat³, H. T. T. Nguyen^1,2

¹M2ISH UMR U1071 INSERM/UdA, ²INRA USC 2018, Clermont-ferrand, ³INRA Theix, Human nutrition unit (UNH), Saint-Genes-Champanelle, France

Contact E-mail Address: hang.nguyen@udamail.fr

Introduction: A high prevalence of the adherent-invasive E. coli (AIEC) in the intestinal mucosa of Crohn’s disease patients has been shown. We previously showed that upon AIEC infection, autophagy is induced in host cells to restrain AIEC intracellular replication. The mechanism underlying such autophagy induction, however, remains largely unknown.

Aims & Methods: Here, we investigated the role of the GCN2/eIF2α/ATF4 pathway in autophagy response to AIEC infection. Autophagic activity was assessed by Western blot and immunofluorescent labelling of LC3. Intracellular bacterial number was determined by bacterial invasion assay and confocal microscopy. Binding of ATF4 to autophagy gene promoters was assessed by Chromatin immunoprecipitation (ChIP) assay. Wild type (WT) and GCN2 knockout (KO) mice were infected with an AIEC reference strain LF82 by gavage.

Results: Infection of human intestinal epithelial T84 cells with the AIEC LF82 strain activated the GCN2/eIF2α/ATF4 pathway as shown by increased phospho-GCN2 and phospho-eIF2α levels, enhanced ATF4 protein expression, and upregulated mRNA expression levels of ATF4 target genes. To explore the role of this pathway in host responses to AIEC infection, we used GCN2-deficient mouse embryonic fibroblasts (GCN2^-/- MEF). GCN2 depletion suppressed eIF2α activation and inhibited the increase in ATF4 protein level induced by LF82 infection. mRNA expression levels of the autophagy genes p62, MAP1lc3, Beclin1, atg3 and atg7 were significantly increased in WT MEF upon LF82 infection, and this was blocked in GCN2^-/- MEF. ChIP assay showed that GCN2 depletion inhibited the LF82-induced binding of ATF4 to the promoters of these autophagy genes. Consequently, autophagy induction upon LF82 infection was suppressed in GCN2^-/- MEF, leading to increased LF82 intracellular replication and elevated pro-inflammatory cytokine production, compared to WT MEF. In vivo study consistently showed that LF82 infection activated the GCN2/eIF2α/ATF4 pathway in enterocytes from WT mice, but not GCN2 KO mice. In response to AIEC infection, autophagy was induced in WT mouse-derived enterocytes, and this was not observed in KO mice. LF82 persistence in the gut was increased in KO mice, leading to aggravated intestinal inflammation, compared to that in WT mice. Depletion of GCN2 did not affect susceptibility of mice to DSS-induced colitis, indicating that the effects obtained were not a consequence of inflammation and were specific for AIEC infection.

Conclusion: The GCN2/eIF2α/ATF4 pathway is activated in host cells during AIEC infection, which is served as a defense mechanism to induce a functional autophagy to control AIEC intracellular replication.

Disclosure of Interest: None declared

P0274 EPIGENETIC MECHANISMS OF AIEC-RECEPTOR CEACAM6 REGULATION IN CROHN’S DISEASE: CHROMATIN REMODELLING AND MICRO-RNA SIGNATURES

A. Agus¹, J. Denizot¹, G. Sevrin¹, H. T. Nguyen¹, N. Barnich¹

¹Clermont Université, M2iSH, UMR 1071 INSERM/Université d'Auvergne, Clermont-Ferrand, France Unité Sous Contrat 2018 Institut National de la Recherche Agronomique, Clermont-Ferrand, France

Introduction: Abnormal expression of CEACAM6 is observed at the apical surface of the ileal epithelium in Crohn’s disease (CD) patients. This allows Adherent-Invasive Escherichia coli (AIEC) to colonize gut mucosa, leading to development of inflammation. Our aims were to understand the regulation of CEACAM6 expression in CD ileal mucosa and to investigate epigenetic mechanisms involved in CEACAM6 overexpression during AIEC infection.

Aims & Methods: HIF-1α and histone H3 Serine 10 phosphorylation (H3S10p) levels were measured in CEACAM6 promoter region by chromatin immunoprecipitation (ChIP). MicroRNAs (miRNAs) that potentially target CEACAM6 were predicted by in silico algorithms. MiRNA levels in human intestinal epithelial T84 cells were measured using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Luciferase assays were used to assess binding of predictive miRNAs to the 3’-untranslated region (3’-UTR) of CEACAM6 mRNA. Effect of transfection of predictive microRNA precursors on CEACAM6 expression in T84 cells was analyzed by Western blot. Impact of AIEC infection on miRNA levels in T84 cells was analyzed by qRT-PCR.

Results: Higher expression of CEACAM6 was observed in T84 cells compared to Caco-2 cells. This was associated with high binding of HIF-1α on the CEACAM6 gene promoter in an open chromatin state region characterized by increased H3S10 phosphorylation level. In contrast, Caco-2 cells expressed low levels of CEACAM6 due to a compact chromatin state in CEACAM6 promoter (low level of H3S10p). AIEC infection led to an increase in CEACAM6 expression related to enhance HIF-1α binding to CEACAM6 promoter. Abnormal H3S10 phosphorylation in CEACAM6 promoter following AIEC infection enhanced HIF-1α binding and subsequent CEACAM6 expression. Moreover, in silico analysis predicted several miRNAs that are potentially able to regulate CEACAM6 expression. Luciferase reporter assays showed that among the predictive miRNAs, 11 hsa-miRNAs (in particular 29a-3p, 424-3p and 489-3p) directly bound to the 3’-UTR of CEACAM6 mRNA. Interestingly, expression of some of these miRNAs was altered after AIEC infection.

Conclusion: This study suggests that AIEC bacteria have the ability to modulate gene expression in the host cell for their own benefit by altering different epigenetic marks as miRNA expression profile and histones post-translational modifications enhancing CEACAM6 abnormal expression. Thus, epigenetic pathways could be new targets to prevent AIEC colonization and AIEC-induced inflammation in CD patients.

Disclosure of Interest: None declared

P0275 VITAMIN D POTENTIATES THE IMMUNOSUPPRESSIVE EFFECT OF ANTI-TNF INDUCED MACROPHAGES

A. Levin¹, M. Wildenberg^1,2, P. Koelink¹, F. Bloemendaal¹, G. D'Haens², G. Van den Brink^1,2

¹Tytgat Institute for Liver and Intestinal Research, ²Department of Gastroenterology & Hepatology, Academic Medical Center, Amsterdam, Netherlands

Contact E-mail Address: a.d.levin@amc.uva.nl

Introduction: We have previously shown that anti-TNF treatment of mixed lymphocyte reactions (MLR) results in the induction of macrophages with immunosuppressive and wound healing properties. In patients who respond to IFX treatment, the number of these macrophages increases significantly in the intestine. In contrast, no increase is seen in non-responders, indicating the clinical importance of this cell population. Because Vitamin D has an immunosuppressive effect on immune cells, we wanted to determine the role of vitamin D in anti-TNF induced macrophages. The aim of this study was to determine if the Vitamin D receptor pathway was activated in anti-TNF induced macrophages and if Vitamin D can potentiate immunosuppressive effect of these macrophages.

Aims & Methods: Peripheral blood mononuclear cells (PBMC) were isolated from peripheral blood of healthy donors. MLR were established by co-culturing PBMC of two healthy donors in a 1:1 ratio. Cultures were treated with anti-TNF to induce anti-TNF induced macrophages. IFN- γ induced macrophages were generated by culturing monocytes in the presence of IFN-γ. Gene expression of anti-TNF compared to IFN-γ induced macrophages was determined by microarray or by real-time PCR. Protein expression of the Vitamin D receptor (VDR) was determined by western blot.

To determine the effect of Vitamin D on IFN-γ and anti-TNF induced macrophages cell culture experiments were performed in the presence or absence of 1.25-dihydroxyvitamin D.

Anti-TNF induced macrophages were isolated with CD14 microbeads and co-cultured with activated T-cells from a third donor. Subsequently T-cell proliferation was measured by 3H thymidine incorporation.

Results: Anti-TNF induced macrophages displayed increased expression of a number of components of the vitamin D receptor pathway including the transcripts for VDR, Osteopontin and the Retenoid X receptor. In line with this, anti-TNF induced macrophages showed increased VDR protein expression compared to IFN-γ induced macrophages, confirming the results of the micro array. Furthermore anti-TNF induced macrophages showed increased expression of the VDR response gene cathelicidin antimicrobial peptide after treatment with 1.25-dihydroxyvitamin D. Indicating increased capacity to respond to Vitamin D.

In order to determine if Vitamin D could enhance the immunosuppressive effect of anti-TNF induced macrophages, macrophages were generated in the presence of the active metabolite of vitamin D. Addition of active vitamin D did not alter the number of regulatory macrophages. However anti-TNF induced macrophages generated in the presence of 1.25-dihydroxyvitamin D did show an increased capacity to inhibit of T-cell proliferation.

Conclusion: Anti-TNF induced macrophages show an increased activation of the vitamin D receptor pathway. The immunosuppressive properties of anti-TNF induced macrophages can be potentiated by 1.25-dihydroxyvitamin D.

Disclosure of Interest: A. Levin: None declared, M. Wildenberg: None declared, P. Koelink: None declared, F. Bloemendaal: None declared, G. D'Haens Conflict with: has served as speaker, consultant, and principal investigator for Abbott/AbbVie, AM Pharma, Centocor/Janssen Biologics, Engene, Photopill, Setpoint, Novo Nordisk, MSD, UCB, Takeda, TEVA, Millenium, Boehringer Ingelheim, Elan, Ferring Pharmaceuticals, Dr Falk Pharma, Shire, Cosmo, AstraZeneca, GSK, and PDL., G. Van den Brink Financial support for research: PPM services, Crucell and AbbVie, Lecture fee(s): AbbVie, Merck Sharp & Dohme, and Ferring Pharmaceuticals, Consultancy: AbbVie

P0276 THE AUTOPHAGY-RELATED PROTEIN CATHEPSIN S IS ESSENTIAL FOR THE INDUCTION, VIABILITY AND M2 PHENOTYPE OF ANTI-TNF INDUCED MACROPHAGES

A. Levin¹, P. Koelink¹, F. Bloemendaal¹, C. Vos², G. D'Haens³, G. Van den Brink^1,3, M. Wildenberg^1,3

¹Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, ²Depart of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, ³Department of Gastroenterology & Hepatology, Academic Medical Center, Amsterdam, Netherlands

Contact E-mail Address: a.d.levin@amc.uva.nl

Introduction: We have previously shown in vitro and in vivo that anti-TNFs induce macrophages with immunosuppressive and wound healing properties. These macrophages express the M2 macrophage phenotype marker CD206. Furthermore anti-TNF induced macrophages have increased levels of autophagy and our in vitro studies have shown that the presence of the wild type allele of ATG16L1 is associated with an increase of anti-TNF induced macrophages. The aim of this study was to further understand the effect of autophagy on anti-TNF induced macrophages.

Aims & Methods: In order to generate anti-TNF induced macrophages mixed lymphocyte reactions (MLR) were performed with peripheral blood mononuclear cells from healthy donors in the presence of anti-TNF. Anti-TNF induced macrophages were isolated by magnetic bead separation using CD14+ microbeads. IFN-γ induced macrophages were generated by culturing human monocytes in the presence of IFN-γ. Expression profile of 84 autophagy related transcripts was determined by real-time PCR array. Protein expression for Cathepsin S was determined by western blot. CD206 expression was determined by flow cytometry and viability was determined by MTS assay.

Results: Anti-TNF-induced macrophages had a different expression profile of autophagy-related transcripts compared to macrophages induced with IFN-γ. Interestingly Cathepsin S was highly upregulated in the anti-TNF-induced macrophages. Because Cathepsin S is a lysosomal protease that has previously been shown to induce M2 polarization in an autophagy dependent manner, we wanted to further study the effect of Cathepsin S on anti-TNF-induced macrophages.

Anti-TNF-induced macrophages showed increased Cathepsin S protein expression compared to IFN-γ-induced macrophages, confirming the results of the RNA array. We then tested the functional role of Cathepsin S in these macrophages. Addition of Cathepsin S inhibitor abrogated the capacity of anti-TNF to induce CD206+ macrophages. Furthermore anti-TNF-induced macrophages isolated from MLR and subsequently cultured in the presence of Cathepsin S inhibitor showed decreased viability and decreased expression of the M2 phenotype marker CD206.

Conclusion: The autophagy-related protein Cathepsin S is highly expressed in anti-TNF-induced macrophages and is essential for the induction, viability and M2 phenotype of anti-TNF-induced macrophages.

Disclosure of Interest: A. Levin: None declared, P. Koelink: None declared, F. Bloemendaal: None declared, C. Vos: None declared, G. D'Haens Conflict with: has served as speaker, consultant, and principal investigator for Abbott/AbbVie, AM Pharma, Centocor/Janssen Biologics, Engene, Photopill, Setpoint, Novo Nordisk, MSD, UCB, Takeda, TEVA, Millenium, Boehringer Ingelheim, Elan, Ferring Pharmaceuticals, Dr Falk Pharma, Shire, Cosmo, AstraZeneca, GSK, and PDL., G. Van den Brink Financial support for research: PPM services, Crucell and AbbVie, Lecture fee(s): AbbVie, Merck Sharp & Dohme, and Ferring Pharmaceuticals, Consultancy: AbbVie, M. Wildenberg: None declared

P0277 INFLIXIMAB PROMOTES MEGAKARYOCYTE DEVELOPMENT AND PRO-PLATELET RELEASE IN INFLAMMATORY BOWEL DISEASE PATIENTS

M. Guerci¹, A. Balduini², A. Malara³, C. Salvatore¹, D. Bagordo¹, A. Caprotti¹, G. Davì⁴, G. R. Corazza¹, A. Di Sabatino¹

¹First Department of Medicine, ²Department of Molecular Medicine, Laboratory of Biotechnology, IRCCS San Matteo Foundation, ³Department of Molecular Medicine, Laboratory of Biotechnology, IRCCS Policlinico San Matteo, Pavia, ⁴Department of Medicine and Aging Center of Excellence on Aging, University of Chieti-Scalo, Chieti-Scalo, Italy

Contact E-mail Address: a.disabatino@smatteo.pv.it

Introduction: Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory disorders of the small intestine and colon. Tumor necrosis factor (TNF)-a mediates multiple pro-inflammatory signals and plays a central role in the pathogenesis of IBD. The monoclonal anti-TNF-a antibody infliximab is effective in the induction and maintenance of clinical remission in patients with IBD. Therefore, we studied the in vitro effect of infliximab on megakaryocyte development and pro-platelet release in IBD

Aims & Methods: Blood samples were collected from five clinically active IBD patients (two with CD and three with UC; males n=3; mean age 38.2 yrs, range 24-64). CD45 positive cells were separated by immunomagnetic selection and cultured for two weeks in the presence of 10 ng/mL thrombopoietin together with eitgher 10 mg/mL infliximab or its isotype control (human IgG1). At the end of the culture, CD61 positive megakaryocytes and pro-platelet-forming megakaryocytes were analyzed by flow cytometry. Blood samples were also collected from five IBD (4 males, mean age 38 yrs, min 25 yrs, max 71 yrs) patients before and after 6 weeks of infliximab treatment at the dose of 5 mg/kg administered at week, 0, 2 and 6.

Results: No significant difference in in vitro megakaryocyte differentiation was observed in cultures stimulated with either infliximab or IgG1. However, mature megakaryocytes exhibited a significantly (p < 0.001) higher capacity in releasing pro-platelets in the presence of infliximab compared to megakaryocytes cultured in the presence of IgG1. Furthermore, hematopoietic progenitor cells derived from the blood of IBD patients after in vivo infliximab treatment showed a significantly (p < 0.05) higher in vitro differentiation in megakaryocytes in comparison to cells collected before the infiximab treatment.

Conclusion: These findings showed that infliximab promotes in vitro pro-platelet release in IBD patient-derived megakaryocyte cultures. Further experiments are needed to clarify whether the infliximab-induced development of pro-platelets might have a role in the wound-healing process sustained by the anti-TNF-a treatment.

Disclosure of Interest: None declared

P0278 COMPARISON OF GEBOES SCORE AND SIMPLIFIED GEBOES SCORE WITH MAYO ENDOSCOPIC SUBSCORE IN PATIENTS WITH RECENT DIAGNOSIS OF ULCERATIVE COLITIS: A RETROSPECTIVE STUDY

A. Jauregui-Amezaga¹, A. Geerits², Y. Das², B. Lemmens², T. Bessissow³, T. Lobatón⁴, M. Ferrante⁵, G. Van Assche⁵, R. Bisschops⁵, K. Geboes², G. De Hertogh², S. Vermeire⁵

¹Gastroenterology, University Hospitals Leuven - KU Leuven, Leuven, Spain, ²Pathology, University Hospitals Leuven - KU Leuven, Leuven, Belgium, ³Gastroenterology, Mc Gill University Health Center, Montreal, Bahrain, ⁴Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain, ⁵Gastroenterology, University Hospitals Leuven - KU Leuven, Leuven, Belgium

Contact E-mail Address: aran.jauregui@gmail.com

Introduction: The Geboes Score (GS) is the most commonly used histological score in ulcerative colitis (UC).¹ A Simplified Geboes Score (SGS) that only includes variables linked to active inflammatory disease has been proposed in a previous study.² The aim of this study was to compare both scores, and to assess their correlation with the endoscopic findings in patients recently diagnosed with UC and followed up over 5 years.

Aims & Methods: Patients diagnosed with UC between 2005 and 2010, and who had serial endoscopies and biopsies, were retrospectively included. The 5-year histological evolution after diagnosis was recorded. Endoscopic results were recorded based on Mayo Endoscopic Subscore. Histological activity was scored by an experienced pathologist with the GS and the SGS. Conversions were constructed to compare endoscopic/histological scores: 2 conversions from the GS based on the results of a previous study (conversions 3 and 9) and 3 conversions from the GSG were tested, combining grade 1 and 2 (conversion 1), grade 2 and 3 (conversion 2), and grade 3 and 4 (conversion 3) of SGS.³

Results: We analysed 339 colonoscopies and their corresponding biopsies obtained from 103 patients with UC (51% women, mean age 40). Twenty-nine (28%) patients had proctitis, 46 (45%) left-sided colitis, and 28 (27%) extensive colitis. Forty (12%) colonoscopies presented Mayo 0, 74 (22%) Mayo 1, 107 (31%) Mayo 2, and 117 (35%) Mayo 3. A comparison of endoscopic and both histological scores of the 339 colonoscopies was performed (see Table). Patients in endoscopic remission (Mayo 0) presented with active microscopic disease (≥ Grade 3.1) in 23% of cases and those with Mayo 1 in 84%. The correlation analysis between endoscopy and both GS and SGS assessed by Kendall rank correlation coefficient (kendall τ, p value) did not show significant differences between the 2 histological scores: GS-conversion 3 (0.51, <0.001), GS-conversion 9 (0.51, <0.001), SGS-conversion 1 (0.48, <0.001), SGS-conversion 2 (0.48, <0.001), and SGS-conversion 3 (0.48, <0.001).

GEBOES S.		Mayo 0	Mayo 1	Mayo 2	Mayo 3	Total
Grade 0	0.00.10.20,3	91300	3300	0000	0000	121600
Grade 1	1.11.21.3	800	600	200	100	1700
Grade 2	2.12.22.3	100	000	100	000	200
Grade 3	3.13.23.3	200	100	300	100	700
Grade 4	4.14.24.3	000	101	111	000	212
Grade 5	5.15.25.35.4	5101	2523101	3334301	21284621	84868624
SIMPLIFIED GEBOES S.		Mayo 0	Mayo 1	Mayo 2	Mayo 3	Total
Grade 0		30	12	2	1	45
Grade 1	1.11.2	00	00	00	00	00
Grade 2	2.12.2	10	00	10	00	20
Grade 3	3.13.2	20	10	30	10	70
Grade 4	4.14.24.34.4	0601	147121	267311	0494621	31698924
Total		40	74	107	118	339

Conclusion: The assessment of histological activity based on the original GS and the SGS in a population of recently diagnosed active UC patients was comparable. Further validation should be performed in order to replace the original Geboes Score with the Simplified Geboes Score for the assessment of histological activity in UC patients’ biopsies.

Disclosure of Interest: None declared

P0279  PREDICTIVE FACTORS OF BONE LOSS IN INFLAMMATORY BOWEL DISEASE

A. Hammami¹, A. Ben Slama¹, H. Jaziri¹, M. Ksiaa¹, A. Souguir¹, I. Ben Mansour¹, S. Ajmi¹, A. Brahem¹, A. Jmaa¹

¹University hospital of Sahloul, Sousse, Tunisia

Contact E-mail Address: aya_med@hotmail.fr

Introduction: Patients with Inflammatory Bowel Disease (IBD) are at increasing risk of developing disorders in bone and mineral metabolism. Osteopenia and osteoporosis are frequent but often underestimated complications in these patients. Several factors could contribute to osteopenia, but the pathogenetic mechanisms are still not completely understood. The aim of this study is to assess the prevalence and the risk factors associated with bone loss in IBD patients.

Aims & Methods: We conducted a retrospective study from January 2007 to June 2012, including all patients with IBD who attended our department. Bone mineral density (BMD) was measured with diphotonic x-ray absorptiometry of the lumbar spine and the neck of the left femur. Results were expressed as T score (osteopenia: -2.5 standard deviation (SD) < T< -1 SD, osteoporosis: T<-2.5 SD) according to the World Health Organization (WHO).

Results: 146 patients with IBD were included, 105 had Crohn's disease (CD) (71.9%), and 41 had ulcerative colitis (UC) (28.1%). The average age at diagnosis was 33.18 years [18-46]. BMD was normal in 61 patients (41.8%) and reduced in 85 patients (58.2%). 57 cases had osteopenia (39%) and 28 patients had osteoporosis (19.2%). In patients with Crohn's disease, 60% of cases (63/105) had reduced BMD (osteopenia in 39 cases and osteoporosis in 24 cases). 53.6% of patients with UC (22/41) had reduced BMD (osteopenia in18 cases and osteoporosis in 4 patients). The univariate analysis showed a statistically significant relationship between bone loss and age over 38 years (0.032), an active tobacco consumption (0.049), low calcium intake (p = 0.0001), reduced physical activity (p = 0.024), a lower body mass index, particularly below 20 kg / m2 (p = 0.033), elevated markers of inflammation (p = 0.003), a duration of disease over 12 months (0.049), the extent of disease (0.001), and active disease (0.016), total duration of corticosteroids consumption over 12 months (p = 0.02), and a cumulative dose of corticosteroids > 4.5 g of Prednisone (p = 0.001). In multivariate analysis, the following factors were independently predictive of bone loss: limited physical activity (p = 0.013), body mass index <20 kg / m2 (0.015), active disease (p = 0.035), the extent of the disease (p = 0.006), and a cumulative dose of corticosteroid exceeding 4.5g of Prednisone (p = 0.003).

Conclusion: Bone loss and osteoporosis are commonly reported in patients with IBD. Bone mineral density screening must be conducted systematically for patients with IBD with greater risk related to reduced physical activity, body mass index <20 kg / m2, active disease, extensive disease, and a cumulative dose of corticosteroids > 45g.

Disclosure of Interest: None declared

P0280 ROLE OF RAGE DURING INTESTINAL INFLAMMATION AND ITS THERAPEUTIC POTENTIAL IN IBD

M. Body-Malapel¹, M. Djouina¹, N. Grossin¹, P. Desreumaux¹, A. M. Schmidt², E. Boulanger¹, C. Vignal¹

¹Lille Inflammation Research International Center, UMR 995 INSERM, Lille University, CHRU, Lille, France, ²Department of Medicine, NYU Langone Medical Center, New York, United States

Contact E-mail Address: cecile_vignal@hotmail.com

Introduction: Inflammatory bowel diseases (IBD) are chronic and relapsing, life-long diseases of the gastrointestinal tract. Environmental factors which have a crucial role in the development of these diseases remain largely unknown. Few studies have described Advanced Glycation End-Products (AGE) as potential contributors of intestinal inflammation, and the role of AGE and their receptor RAGE in the pathophysiology of IBD are not yet fully elucidated.

Aims & Methods: The global aim of our study was to address the link between AGE, RAGE, and IBD which might help to better understand the role of nutrition, as a major source for AGE, in the pathophysiology of IBD.

Three different models of intestinal and colonic inflammation (indomethacin, dextran sodium sulfate (DSS) and trinitro benzene sulfonic acid (TNBS)) were induced in C57BL/6 wild type (WT) and RAGE null mice. In a second set of experiments, mice were orally administered with the food derived ligand for RAGE, carboxymethyllysine-bovine serum albumin (CML-BSA) or control BSA for 30 days; then, intestinal and colonic inflammation were induced. Severity of inflammation was evaluated using macroscopic, histologic and molecular parameters in the small intestine and colon of mice.

Results: Following indomethacin administration, a significant decrease in ulcerations number and area was observed in the duodenum, jejunum and ileum of RAGE null mice compared to WT mice. Consistently, IL1b mRNA levels were significantly decreased in the three intestinal segments. RAGE null mice were protected from DSS- and TNBS-induced colitis, with a significant decrease of clinical and macroscopic parameters. Myeloperoxidase (MPO) activity, reflecting the neutrophil infiltration, was also significantly reduced in the colon of TNBS- treated RAGE null mice compared to TNBS- treated WT mice. IL1b and iNOS mRNA expression were significantly decreased in colitic RAGE null mice compared to colitic WT mice. Chronic BSA-CML administration to mice worsened indomethacin-induced enteritis, as evidenced by a significant increase in ulcerations number and area in the duodenum, jejunum and ileum compared to control BSA-treated mice. Consistently, MPO activity and oxidative stress assessed by anion superoxide dosage were significantly increased in the ileum of CML BSA-treated mice compared to control BSA-treated mice. Chronic CML-BSA administration did not induce any effect on colonic inflammation.

Conclusion: We demonstrated that RAGE signaling pathway is implicated in intestinal and colonic inflammation in mice. We showed that BSA-CML might be a dietary factor involved in intestinal inflammation. The role of RAGE and AGE in IBD now merits further investigations.

Disclosure of Interest: None declared

P0281 CASP8 INHIBITION IN CD4+ T CELLS BLOCKS CHRONIC INTESTINAL INFLAMMATION

I. Backert¹, M. Leppkes¹, M. F. Neurath¹, C. Neufert¹

¹University Hospital Erlangen, First Department of Medicine, Erlangen, Germany

Contact E-mail Address: clemens.neufert@uk-erlangen.de

Introduction: Caspase 8 (CASP8) is an aspartate-specific cysteine protease that has been recently linked to inflammatory bowel diseases (IBD), and CD4+ T cells are well-known key players influencing the perpetuation of mucosal inflammation in IBD patients. Previous work identified CASP8 as a central regulator of T cell fate decisions which can exert pro– as well as anti-inflammatory effector functions depending on the cellular and molecular context.

Aims & Methods: The T cell-specific role of CASP8 during intestinal inflammation has not been clarified yet. To address that topic, we have analyzed the potency of FACS-sorted naïve CD4+ T cells from several genetically modified mouse strains to induce intestinal inflammation in the adoptive transfer model of chronic colitis. Serial inspections of colonic inflammation were performed in vivo by mini-endoscopy. In addition, histopathological analyses and immunofluorescence studies were done in colon cross-sections, and immunomonitoring was performed by FACS in lamina propria and mesenteric lymph node cells.

Results: Interestingly, CASP8 deficient T cells failed to induce intestinal inflammation, produced decreased levels of pro-inflammatory cytokines and showed diminished accumulation in immunocompromised hosts, despite being highly resistant to Fas induced apoptosis. Co-transfer of congenic wildtype T cells demonstrated that the CASP8-deficient T cell population expanded less efficiently under the same in vivo conditions as wildtype cells. Additional genetic deletion of RIPK3, but not ATG7 fully restored the colitogenicity of CASP8 deficient T cells, indicating that T cell necroptosis represents a key mechanism for the blockade of intestinal inflammation. Moreover, we could show that pro-inflammatory human T cells from IBD patients can be targeted via RIPK3-RIPK1-kinase-dependent necroptosis.

Conclusion: Our study demonstrates a critical role of CASP8 in CD4+ T cells during chronic intestinal inflammation. Thus, the blockade of CASP8 and induction of necroptosis in CD4+ T cells might emerge as a novel therapeutic strategy for IBD patients.

Disclosure of Interest: None declared

P0282 DENDRITIC CELL COMPARTMENTALIZATION IN THE HUMAN INTESTINAL GUT IN HEALTH AND CROHN'S DISEASE

I. Moret Tatay^1,2, Y. Siaw^1,3, R. Man⁴, H. O. Al-Hassi¹, R. Vora¹, D. Reddi¹, A. L. Hart³, B. Beltran^5,6, P. Nos^5,6, S. C. Knight¹, D. Bernardo¹, on behalf of Dr S.C. Knight and Dr D. Bernardo are both co-senior authors

¹Antigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark's Campus, Harrow, United Kingdom, ²Gastroenterology Dpt, IIS Hospital La Fe, Valencia, Spain, ³Digestive Medicine, St. Mark's Hospital, North West London Hospitals NHS Trust, ⁴Wolfson Unit for Endoscopy, North West London Hospitals NHS Trust, Harrow, United Kingdom, ⁵CIBERehd,, ⁶Gastroenterology Dpt., Hospital La Fe, Valencia, Spain

Contact E-mail Address: agnese2005@hotmail.com

Introduction: Human intestinal dendritic cells (DC) maintain a balance between tolerance to nutrients/commensals and immunogenicity against pathogens. Changes in intestinal DC properties are found in inflammatory bowel diseases including Crohn’s disease (CD). Most studies, however, do not consider DC compartmentalization through the human gut. Here we studied whether DC subsets and phenotype change through the human gut in healthy controls (HC) and CD patients.

Aims & Methods: Paired biopsies from human proximal colon and the terminal ileum (TI) were obtained from HC and CD patients. DC were identified following collagenase digestion where DC phenotype were assessed by flow cytometry. Antigen presenting cells (CD45⁺HLA-DR^high) were identified within single viable cells. Discrimination between DC and Mϕ was subsequently performed based on lineage marker expression (CD3,CD14,CD16,CD19,CD34) and side scatter properties of the cells identifying DC as CD45⁺HLA-DR⁺lineage^-complexity^low. DC were further distinguished from Mϕ as CD64^- with CCR7 up-regulation following overnight culture.

Results: In all samples, intestinal DC were myeloid (mDC, CD11c⁺) and were further divided into different subsets based on CD103 and SIRPα expression. CD103^-SIRPa⁺ and CD103⁺SIRPa⁺were type 1 immature mDC (CD1c⁺CD141^-ILT3⁺) while CD103⁺SIRPa^- were type 2 mature mDC (CD1c^-CD141⁺ILT3^-). CCR2 was expressed in all CD103^-SIRPa⁺ DC, with expression being variable on CD103⁺SIRPa⁺and absent on CD103⁺SIRPa^- DC.

In HC, total DC numbers were higher in the proximal colon compared with the TI with no differences in the CD103/SIRPα DC subset composition between compartments. However, the TI from HC carried higher numbers of CCR2⁺DC and CD11c^dimCD1c^- DC.

In CD patients compared with healthy controls, DC numbers were higher in both the colon and the TI and displayed a specific reduction of CD103⁺SIRPa⁺ DC in both tissues. CCR2 expression on ileal and colonic DC did not differ between HC and CD. In CD, however, the proportion of ileal CD11c^dimCD1c^- DC was lower in CD patients than in HC, an effect that was not seen in the proximal colon. Finally, TLR2 and TLR4 expression were higher in both the colon and TI from CD patients, compared with the healthy matched tissue, due to a specific up-regulation of CD11c⁺CD1c⁺DC.

Conclusion: DC subsets and phenotype change through the length of the human gastrointestinal tract and display different tissue-specific alteration in CD patients. Tissue compartmentalization is, therefore, likely to affect the results of studies addressing the immune system of the human gut, both in health and disease.

Disclosure of Interest: None declared

P0283 EVALUATION OF HUMORAL IMMUNE RESPONSE TO CLOSTRIDIUM DIFFICILE INFECTION IN INFLAMMATORY BOWEL DISEASES

D. Mukhametova¹, D. Abdulganieva¹, A. Odintsova²

¹Hospital Therapy, Kazan State Medical University, ²Gastroenterology, Republican Clinical Hospital, Kazan, Russian Federation

Contact E-mail Address: muhdilyara@gmail.com

Introduction: Disorder of intestinal microbes is thought to play a critical role in the pathogenesis of inflammatory bowel diseases (IBD). Evaluation of bacterial Ig could become a new approach to judge the situation of this disease.

Aims & Methods

Aim: to evaluate IgA, IgM and IgG levels to Clostridium difficile infection (CDI) in patients with IBD.

Methods: We prospectively included 147 pts with IBD – 92 pts with ulcerative colitis (UC) (87 in exacerbation and 5 in remission), 55 pts with Crohn's disease (CD) (44 in exacerbation and 11 in remission) and 30 healthy controls. Concentrations of IgA, IgM and IgG to lipopolysaccharide of CDI were evaluated by immunoassay. Mean age in UC was 38.18 ± 1.23 years, CD – 28.04 ± 2.11 and in control group – 30.13 ± 1.53. Severity of UC was assessed by Mayo score: mild – 28 (32.2%), moderate – 43 (49.4%), severe – 16 (18.4%). Severity of CD was assessed CDAI: mild – 15 (34%), moderate – 16 (36.4%), severe – 13 (29.6%).

Results: There was increasing of IgA, IgM and IgG levels to CDI in UC and CD compared to controls (Table 1).

Table 1.

IgA, IgM and IgG levels to Clostridium difficile infection

	Ig A	Ig M	Ig G
control group	0.009 ± 0.005	2.99 ± 0.4	1.76 ± 0.27
exacerbation of UC	0.017 ± 0.003	5.46 ± 0.41***	6.49 ± 1.13***
remission of UC	0.06 ± 0.05	5.77 ± 2.09	6.05 ± 3.17
exacerbation of CD	0.02 ± 0.003**	6.09 ± 0.79**	8.74 ± 2.0***
remission of CD	0.12 ± 0.002	4.36 ± 1.06	5.83 ± 3.11*

*p < 0.01 v. control, **p < 0.005, ***p < 0.001

Immune response to CDI correlated with clinical parameters of IBD: in CD with IgM increasing faeces were more loose (r=–0.29; p < 0.05); in UC the increasing of IgA to CDI correlates with defecation rate decreasing (r=-0.23; p < 0.05), loosing of faeces (r=-0.27; p < 0.05), less weight loss (r=-0.26; p < 0.05). There is higher level of IgG to CDI in older patients with UC (r=0.24; p < 0.05). In UC the increasing of IgA to CDI correlates with gamma-globulin blood level (r=0.31; p < 0.05), alpha 1-globulin level increases with increasing of IgG to CDI (r=0.30; p < 0.05).

Conclusion: The majority of pts with active IBD have increased IgM and IgG levels to CDI compared to control. Antibodies changes correlated with IBD clinical features and laboratory data.

Disclosure of Interest: None declared

P0284 ACTIVATION OF NLRP3 INFLAMMASOME IN INFLAMMATORY BOWEL DISEASE: DIFFERENCES BETWEEN CROHN’S DISEASE AND ULCERATIVE COLITIS

L.-D. Lazaridis¹, A. Pistiki², E. J. Giamarellos-Bourboulis², M. Georgitsi², G. Damoraki², D. Polymeros¹, G. D. Dimitriadis¹, K. Triantafyllou¹

¹2nd Department of Internal Medicine and Research Institute, ²4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece

Contact E-mail Address: ktriant@med.uoa.gr

Introduction: NLRP3 inflammasome is a multimolecular cytosol complex that when activated contributes to the cleavage of pro-interleukin (IL)-1β to IL-1β via caspase-1 activation¹. NLRP3 activation can derive from both organic and inorganic substances and has been described to have in a variety of auto-inflammatory disorders. Evidence for a role of systemic NLRP3 activation in inflammatory bowel disease (IBD) is still lacking. Herein, we present the final results of our study on inflammasome activation in IBD; prelimenary results were presented at UEGW 2013².

Aims & Methods: Human peripheral blood mononuclear cells (PBMCs) were isolated from 20 Crohn’s disease (CD) patients, 21 ulcerative colitis (UC) patients and 17 controls after gradient centrifugation of heparinized whole blood over Ficoll. PBMCs were stimulated at a density of 5x10⁶/ml with 10 and 0.1ng/ml of the TLR4 ligand lipopolysaccharide (LPS) of Escherichia coli O55:B5 in the absence or presence of different concentrations of NLRP3 stimulant monosodium urate (MSU). After 24h of incubation at 37⁰C at 5%CO₂, concentrations of IL-1β, IL-6 and TNFα were measured in cell supernatants by an enzyme immunoassay. In separate experiments, PBMCs were lysed with Trizol for RNA isolation and measurements of IL-1β gene transcripts by RT-PCR using β2-microglobulin as the housekeeping gene. NLRP3 activation was considered as a more than 30% enhancement of IL-1β production after MSU addition.

Results: NLRP3 activation was found in 12 (75%) patients with CD compared to four (26.7%) controls, (p=0.045) while no significant difference was detected between UC and controls (11/20 or 55% vs. 4/15 or 26.7%, p=0.17), as shown in the table of mean changes of cytokine production and of respective copies. Moreover in CD patients, NLRP3 activation was proportionate to the time since the last intensification of treatment (r=0.95, p < 0.001). Among UC patients, NLRP3 activation was found in eight (72.7%) with late (duration >1.5 years) and in nil with early disease (p=0.03), respectively; no similar association was found in CD patients. No difference was detected regarding changes in IL-6 and TNFα levels and IL-1β transcripts numbers among IBD patients and controls (table). There was no association between NLRP3 activation and disease location, activity, current immunosupressive treatment and smoking status in IBD patients.

	Controls	UC	CD
% change of IL-1β	27.7 ± 26.7	258.6 ± 119.4*	1919.2 ± 1387.3$
% change of IL-6	2428 ± 1997@	822.3 ± 701.4@	919.3 ± 599.3@
% change of TNFα	203.5 ± 100.2#	1675.3 ± 616.6#	779.4 ± 247#
IL-1β transcripts	206.4 ± 188.9^	55.3 ± 25.1^	528 ± 510.1^

*p=0.148 vs. controls, ^$p= 0.032 vs. controls, ^@p > 0.6 (controls vs. UC & CD), ^#p > 0.082 (controls vs. UC & CD), ^{^}p > 0.82 (controls vs. UC & CD)

Conclusion: NLRP3 is activated in CD patients, as compared to controls, and especially in those with long-term intensified treatment. Among UC patients NLRP3 inflammasome activation is detected only in those with long-standing disease.

Disclosure of Interest: L.-D. Lazaridis: None declared, A. Pistiki: None declared, E. Giamarellos-Bourboulis: None declared, M. Georgitsi: None declared, G. Damoraki: None declared, D. Polymeros: None declared, G. Dimitriadis: None declared, K. Triantafyllou Financial support for research: MSD, Lecture fee(s): AbbVie, Takeda

P0285 CIRCULATING PLATELET-DERIVED MICROPARTICLES IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE AND THE IMPACT OF DRUG THERAPY ON THEIR LEVELS

D. Polymeros¹, M. Triantafyllou¹, A. Spathis², G. Tziatzios¹, P. Karakitsos², G. D. Dimitriadis¹, K. Triantafyllou¹

¹2nd Dept Internal Medicine, Medical School, Athens University, ²Department of Cytopathology, “Attikon” University Hospital, Athens, Greece

Contact E-mail Address: ktriant@med.uoa.gr

Introduction: Platelet activation is a consistent feature in inflammatory bowel disease and is thought to contribute to both the proinflammatory and procoagulant states of this disorder. The role of circulating platelet derived microparticles (PDMPs) and the effect of 5-amino salicylate acid (5ASA) and anti-TNF-a agents on their levels has not yet been clarified.

Aims & Methods: The aim of the study is to evaluate the levels of circulating PDMPs, as well as, the effect of 5ASA and anti-TNF-a treatments on these levels in IBD patients. Platelet-rich plasma was isolated from 47 patients with Crohn’s disease (CD), 43 patients with ulcerative colitis (UC) and 26 sex and age-matched healthy controls. Clinical disease activity was assessed by Harvey-Bradshaw index for CD, Mayo score for UC and serological activity by measurement of C-reactive protein (CRP). Drug treatment at the time of blood sampling was recorded. Using flow cytometry, PDMPs were measured as the percentage of CD 36+ microparticles, as well as, the percentage of CD36+ microparticles expressing annexin (a phospholipid binding protein of the platelet surface expressing platelet activation) by total events with appropriate size and scatter; CD36 being a platelet surface marker.

Results: Overall, CD patients have greater percentage of CD36+ microparticles (0.31% ± 0.07% vs. 0.14%± 0.04%, p=0.02) and of CD36+ microparticles expressing annexin (27% ± 2.6% vs. 14.6% ± 2.7%, p=0.002), in comparison with healthy controls. However, there is no correlation of percentages of both microparticles with Harvey-Bradshaw index and CRP. CD patients not receiving 5ASA have also greater percentage of CD36+ microparticles expressing annexin (25.8% ± 2.8% vs. 14.6% ± 2.7%, p=0.005), in comparison with healthy controls. Moreover, CD patients on 5ASA therapy show lower percentage of CD36+ microparticles in comparison with those not receiving 5ASA (0.30% ±0.07% vs. 0.32% ± 0.09%, p=0.048). Anti-TNF-a treatment has no effect on both microparticle percentages in CD patients. In contrast to CD, UC patients have similar percentages of CD36+ microparticles and of CD36+ microparticles expressing annexin, as compared to healthy controls (p=0.06 and p=0.2, respectively), and there is no correlation of percentages of both microparticles and disease activity (Mayo score and CRP). Moreover, 5ASA and anti-TNF-a treatments have no effect on both microparticle percentages in UC patients.

Conclusion: Circulating levels of platelet derived microparticles are increased only in CD but they are not correlated with disease activity. The use of 5ASA is associated with lower levels of CD36+ PDMPs only in CD, while anti-TNF treatment does not influence their levels in CD and UC patients.

Disclosure of Interest: D. Polymeros: None declared, M. Triantafyllou: None declared, A. Spathis: None declared, G. Tziatzios: None declared, P. Karakitsos: None declared, G. Dimitriadis: None declared, K. Triantafyllou Financial support for research: MSD, Angelini, Lecture fee(s): AbbVie, Takeda

P0286 THE ETHANOLIC EXTRACT OF HYLOCEREUS SP. EXERTS ANTI-INFLAMMATORY EFFECTS AND PREVENTS MURINE COLITIS

D. C. Macias Ceja¹, J. Cosín-Roger¹, M. D. Ortiz-Masiá¹, P. Salvador¹, S. Calatayud¹, C. Hernández¹, M. D. Barrachina¹

¹Pharmacology, Faculty of Medicine of Valencia, Valencia, Spain

Contact E-mail Address: yuche_dulce@hotmail.com

Introduction: Inflammatory bowel disease (IBD) is a chronic disorder of the gastrointestinal tract characterized by epithelial barrier disfunction and imbalance immune response. Recent pharmacological treatment has significantly improved the course of the disease but there are still a high percentage of patients that do not respond to current therapies.

Aims & Methods: We aim to evaluate the effects of the ethanolic extract of Hylocerus sp. (EH) in a murine model of colitis induced by TNBS. Colitis was induced in Balb/c mice by the intrarectal administration of TNBS (3.5mg/20g). Control animals received an intrarectal injection of TNBS-vehicle (EtOH 40%) (day 0). Six hours after TNBS, mice received an i.p. injection of EH (20 mg/20g mice) or its vehicle (DMEM). Changes in body weight were determined daily (results are expressed as percentage vs the weigth at day 0) and mice were sacrificed 2 and 4 days after TNBS administration. Mucosal histology was evaluated according to Wallace Score (1-10). Colons were frozen for RNA and protein isolation. The mRNA expression of iNOS, Arginase I, COX-2, TNF-α, IL-1β, IL-6 and IL-10 was analysed by qPCR and protein levels of NF-κB and Iκβ-α were determined by western blot.

Results: Treatment of mice with TNBS induced a loss of body weight that peaked 2 days after treatment. Subsequently, mice began to recover and, four days after treatment, body weight reached similar values to those of control animals. In TNBS-treated mice, the administration of EH significantly (P < 0.05) prevented the loss of body weight (91.97 ± 1.65%) compared with the injection of vehicle (86.40 ± 2.05%), two days after TNBS. Mice receiving the EH exhibited a significant reduction in histological damage score (3.6 ± 0.6) compared with that detected in mice receiving vehicle (7.0 ± 1.0), four days after treatment. The increase in the expression of pro-inflammatory molecules detected 2 days after TNBS was significantly prevented (P < 0.05) by treatment with EH while no significant differences were detected in the expression of the anti-inflammatory molecule IL-10 (Table 1). Iκβ-α degradation and nuclear NF-κβ translocation were detected in the colon of TNBS-treated mice which was significantly prevented in the colon of mice receiving the EH.

Table1.

mRNA expression of different molecules detected in the colon of TNBS-treated mice. Results are expressed as fold induction vs the value obtained in mice that did not receive TNBS.

	iNOS	ArgI	COX-2	TNFα	IL-1β	IL-6	IL-10
Vehicle	5.3 ± 0.2	22.1 ± 4.1	1.7 ± 0.9	8.8 ± 1.9	1.9 ± 0.3	11.8 ± 3.8	1.2 ± 0.2
EH	0.5 ± 0.2	4.1 ± 1.3	0.5 ± 0.1	1 ± 0.2	0.8 ± 0.2	2.0 ± 0.4	1.8 ± 0.3

Conclusion: Systemic administration of the ethanolic extract of Hylocereus sp exerts an anti-inflammatory effect and prevents murine colitis induced by TNBS.

Disclosure of Interest: None declared

P0287 AN INTERPLAY BETWEEN AUTOPHAGY AND ER STRESS COORDINATES INTERLEUKIN-22 DEPENDENT SIGNALS IN THE INTESTINAL EPITHELIUM

K. Aden^1,2, F. Tran¹, M. Falk-Paulsen¹, A. Luzius¹, J. Kuiper¹, R. Häsler¹, R. Sheibani-Tezerji¹, S. Schreiber^1,2, R. S. Blumberg³, A. Kaser⁴, P. Rosenstiel¹

¹Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, ²1st Department of Medicine, University Hospital Schleswig-Holstein, Kiel, Germany, ³Gastroenterology Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States, ⁴Division of Gastroenterology and Hepatology, Department of Medicine, Addenbrooke’s Hospital, University of Cambridge, Cambridge, United Kingdom

Contact E-mail Address: f.tran@ikmb.uni-kiel.de

Introduction: Endoplasmic reticulum (ER) function and autophagy are necessary to maintain cellular homeostasis. Genetic variants of inflammatory bowel disease (IBD) risk genes like ATG16L1 or XBP1 are associated with epithelial ER stress. While XBP1 plays a beneficial role in resolving ER stress, altered function of ATG16L1 leads to defective autophagy and subsequent deregulation of ER function. ER stress impairs intestinal immune defense against pathogens and promotes cell death. Interleukin (IL) 22 is known to be a protective cytokine in mucosal regeneration through downstream expression of antimicrobial peptides and epithelial proliferation via STAT3 activation, respectively.

Aims & Methods: In this study, we investigate the impact of IBD risk genes ATG16L1 and XBP1 on regenerative function of IL22 in intestinal epithelium. Human colon carcinoma cells (HT-29 and CaCo-2) were treated with recombinant IL22 and ER stress inductors like Tunicamycin and were subjected to wound healing assays, gene expression analysis and immunoblot analysis. Intestinal organoids derived from Xbp1 ΔIEC and Atg16l1 ΔIEC mice were generated by culturing small intestinal crypts in collagen matrix. These were treated with recombinant IL22 and subjected to gene expression analysis. Organoids were subjected to RNA sequencing and transcriptome analysis. Secreted cytokines in supernatants from cells and organoids were detected with ELISA.

Results: IL22 induces transient self-limiting ER stress in the intestinal epithelium. Regulation of transient ER stress is dependent on Xbp1 and Atg16l1 as IL22 treated intestinal organoids from Atg16l1 ΔIEC und Xbp1 ΔIEC mice display a dramatic increase of inducible ER stress and pro-inflammatory gene expression. While IL22 improves wound healing in the absence of ER stress, IL22 leads to impaired wound closure and increased cell death under ER stress conditions. This effect is dependent on STAT3 and autophagy as STAT3 inhibition or autophagy induction through rapamycin completely neutralizes IL22 induced detrimental effect.

Conclusion: These data suggest an unexpected role of the IBD risk genes ATG16L1 and XBP1 in coordinating regenerative IL22 function in intestinal epithelium.

Disclosure of Interest: None declared

P0288 MAGNESIUM IN INFLAMMATORY BOWEL DISEASE: AN UNEXPECTED PLAYER

F. Scaldaferri¹, V. Petito¹, D. Arduini², W. Hamersma², V. Trapani², A. Poscia³, V. Arena², E. Stigliano², A. Di Agostini¹, F. I. Wolf², A. Gasbarrini¹

¹Internal Medicine Department, Gastroenterology division, ²Department of Pathology, ³Department of Hygiene, Catholic University of Sacred Heart of Rome, Rome, Italy

Contact E-mail Address: valepetito88@gmail.com

Introduction: Magnesium is an essential mineral that is fundamental in many pathophysiological processes. A mild hypomagnesaemia is a common condition associated to dietary deficiency of magnesium. Hypomagnesaemia is a well-known enhancer of oxidative stress and inflammation. Inflammatory Bowel Disease (IBD) is a collection of chronic inflammatory bowel diseases characterised by a variety of nutritional deficiencies due to reduced absorption and/or increased loss of essential nutrients, which among other conditions, can induce hypomagnesaemia.

Aims & Methods: To investigate the influence of magnesium availability in the diet on the severity of murine dextran sodium sulphate (DSS)-induced acute colitis. Mice were exposed to 2.5% DSS in the drinking water and fed three different diets (low (30mg/kg), normal (1000mg/kg) and high (4000mg/kg) magnesium content). Both acute colitis (5 days exposure to DSS) and recovery after the acute colitis (7 days of recovery without DSS) were studied. The severity of the colitis was scored daily using a four-point Disease Activity Index (DAI) based on the faecal consistency, weight loss and faecal blood loss. Colon, kidney and serum were collected at the sacrifice. Magnesaemia was analysed using atomic absorption spectrometry and severity of the inflammation of the colon was scored on morphological examination of haematoxylin/eosin stained slides.

Results: Dietary magnesium deficiency increased the severity of the DSS-induced colitis as scored with the Disease Activity Index, whereas magnesium supplementation seemed to score more or less like controls. Serum magnesium measurements showed that while magnesium in the diets positively correlated with the magnesaemia, the exposure to DSS reduced magnesaemia in all conditions. However, high magnesium content in the diet compensated for DSS-induced hypomagnesaemia (the colitic mice on the magnesium-enriched diet showed a magnesaemia similar to the control group on the normal magnesium diet). Interestingly, morphological analysis of the colon showed that while the low magnesium diet enhanced mucosal damage and impaired mucosal recovery, magnesium supplementation clearly protected the colonic mucosa against DSS-induced damage (much less crypt destruction and inflammatory infiltrates). And after recovery the colonic mucosa of the mice on the magnesium-enriched diet appeared to be absolutely normal.

Conclusion: Magnesium supplementation protects the colonic mucosa, compensates inflammation-induced hypomagnesaemia and seems to help the colonic mucosa restore after acute colitis. Our data suggest an active role of magnesium in the pathogenesis and in the severity of colon inflammatory diseases. The validation of these results in IBD patients is currently under study.

Disclosure of Interest: None declared

P0289 TOLL2- AND TOLL9-DERIVED SIGNALS IN DROSOPHILA MELANOGASTER PRESERVE THE INTEGRITY OF MIDGUT NEURONS

G. Schirato¹, M. Pasqualin¹, P. Brun¹, L. Spagnol¹, M. Scarpa², V. Russo¹, G. Palù¹, I. Castagliuolo¹

¹Molecular Medicine, University of Padova, ²IOV Istituto Oncologico Veneto, Padova, Italy

Contact E-mail Address: ignazio.castagliuolo@unipd.it

Introduction: The gut microbiota-innate immunity axis guarantees the development, and the functional integrity of the intestine including the nervous system (ENS) embedded in the gut wall. However, the complexity of animal models is a substantial obstacle to dissect the cellular populations and the molecular pathways involved in this interplay. Since many components of innate immunity, including the sensors for conserved microbial structures such as Toll genes and Toll like receptors, are shared between Drosophila melanogaster and mammals we aimed to identify the enteric cellular populations generating trophic signals, that secure gut neuronal integrity through the Toll pathways using the Drosophila model.

Aims & Methods: We ablated Toll genes in adult flies by the expression of siRNA using ubiquitous (actin and beta-tubulin) and cellular specific (smooth muscle cells, neurons and glia) temperature inducible drivers. After 8 days of Toll genes silencing we: 1) dissected flies gut (20-30 individuals/measure) to perform quantitative RT-PCR for Toll1÷9 and Elav (a neuronal marker) gene expression; 2) executed immunohistochemistry on gut whole mount preparations using a neuronal (anti-HRP) marker to quantify neuronal bodies in the flies midgut; 3) exposed flies to an intestinal toxic (5% DSS) and daily recorded survival (n=60-90 individuals/group).

Results: In Drosophila lines the expression of specific siRNA under the control of ubiquitous drivers significantly reduced in the gut the mRNA levels of Toll1 (by 82%), Toll2 (by 99%), Toll4 (by 80%), Toll6 (by 38%), Toll7 (by 96%), Toll8 (by 85%), Toll9 (by 95%), as compared to W^III8 control (p < 0.01). The number of neuronal bodies in the midgut was significantly reduced by the silencing of Toll2 and Toll9 (p<0.01) but not by the other Tolls. Using the ubiquitous drivers actin and tubulin Toll2 silencing reduced neurons by 92% and 81%, whereas Toll9 silencing diminished neurons by 95% and 93% as compared to W^III8 controls. In agreement to the loss of neurons in the midgut, Elav mRNA was reduced by 80% and 85%, respectively, in the gut of flies with ubiquitous Toll2 or Toll9 silencing. By using specific drivers to silence Toll2 in smooth muscle and glial cells, Toll2 mRNA levels were significantly reduced (p<0.01 vs W^III8 control) in the gut. Accordingly, the number of neuronal bodies in the midgut and the Elav mRNA levels were reduced by 43% and 50% by using the smooth muscle driver and by 85% and 40%, by using the glial cells driver, respectively.

Ubiquitous Toll2 or Toll9 silencing reduced mortality by 32% and 31%, respectively, at the 5^th day of DSS administration as compared to W^III8. While Toll2 silencing in smooth muscle cells had a protective effect reducing mortality by 30%, Toll2 silencing in glial cells exacerbated colitis inducing mortality in 95% of individuals as opposed to 86% of W^III8 (p < 0.01).

Conclusion: Loss of Toll2- and Toll9-derived signals is associated to significant reduction of neuronal bodies in the Drosophila midgut. By using the Drosophila model was possible for the first time to observe that Toll2 silencing has opposite effects in smooth muscle cells and glial cells, supporting specific effects of innate immunity-microbes interplay in specific intestinal cell population.

Disclosure of Interest: None declared

P0290 MUCOSAL FUNGAL MICROBIOTA DYSBIOSIS IN CROHN’S DISEASE

G. Liguori¹, B. Lamas^2,3, M. Lavie-Richard², G. Brandi⁴, G. Da-Costa², T. W. Hoffmann², M. P. Di-Simone¹, C. Calabrese¹, G. Poggioli¹, P. Langella², M. Campieri¹, H. Sokol^2,5

¹Department of Medical and Surgical Science, University of Bologna, Bologna, Italy, ²UMR1319 MICALIS, INRA, Jouy-en-Josas, ³ERL INSERM U 1157/UMR7203, Université Pierre et Marie Curie (UPMC), Paris, France, ⁴Department of Specialistic, Diagnostic and Sperimental Medicine, University of Bologna, Bologna, Italy, ⁵Service de Gastroentérologie et Nutrition, Hôpital Saint Antoine, APHP, Paris, France

Contact E-mail Address: liguori.gy@gmail.com

Introduction: The gut microbiota is involved in many physiological functions. An imbalance in its composition named dysbiosis is associated with several diseases and particularly with inflammatory bowel diseases (IBD). Mucosa associated microbiota, that has been shown to differ from faecal one, could have a key role in induction of host immunity and in inflammatory process. Although the role of fungi has been suggested for a long time in IBD pathogenesis, the fungal microbiota has been poorly explored. The aim of the current study was to analyzed the composition of the mucosa associated microbiota of Crohn’s disease (CD) patients and healthy subjects (HS) taking into account both bacterial and fungal fractions.

Aims & Methods: Bacterial and fungal composition of mucosa associated microbiota of 23 CD patients (16 in flare and 7 in remission) and 10 healthy subjects (HS) was determined using 16S (MiSeq) and ITS2 (pyrosequencing) respectively. The obtained sequences were analyzed using the Qiime pipeline to assess composition, alpha and beta diversity. Comparisons between clinical groups were performed using Linear Discriminant Analysis Effect Size (LEFSE). Global fungal load was assessed by real time PCR.

Results: Bacterial microbiota in CD patients was characterized by a restriction in biodiversity, a decrease of Firmicutes and Bacteroidetes and an increase of Proteobacteria and Fusobacteria. Global fungi load was significantly increased in CD flare compared to HS (p< 0.05). No significant difference in fungi biodiversity was observed between the studied groups. Both in HS and CD, the colonic mucosa-associated fungal microbiota was dominated by Basidiomycota and Ascomycota phyla. Dioszegia genera and Candida glabrata species were overrepresented in CD whereas Leptosphaeria and Trichosporon genera were decreased. Saccharomyces cerevisiae and Filobasidium uniguttulatum species were associated with non inflamed mucosa whereas Xylariales order was associated with inflamed mucosa.

Conclusion: Our study confirms an alteration of the bacterial microbiota and demonstrates the existence of an altered fungal microbiota in CD patients. These alterations are characterized by an increased fungal load in CD and an abnormal composition suggesting that fungi may play a role in CD pathogenesis.

Disclosure of Interest: None declared

P0291 ACTIVATION OF AUTOPHAGY BY CROHN'S DISEASE-ASSOCIATED E. COLI IS DEPENDENT OF SIDEROPHORE EXPRESSION

G. Dalmasso¹, H. T. T. Nguyen¹, T. Faïs¹², S. Massier¹, J. Delmas^1,2, N. Barnich¹, R. Bonnet^1,2

¹University of Auvergne, ²Laboratory of Bacteriology, Clermont-Ferrand Hospital, Clermont-Ferrand, France

Contact E-mail Address: guillaume.dalmasso@udamail.fr

Introduction: The intestinal mucosa of Crohn's disease patients are abnormally colonized by Escherichia coli able to invade and to replicate inside intestinal epithelial cells. Those pathogenic bacteria have been named adherent-invasive E. coli or AIEC. Genomic analysis of the AIEC reference strain LF82 has revealed a pathogenicity island of ∼34kb (PAI II, for pathogenicity island II) closely related to the “high pathogenicity island” of pathogenic Yersinia sp. that encodes the yersiniabactin siderophore system. Bacteria have developed efficient high affinity iron uptake systems (siderophores) promoting their growth in iron-restricted environments.

Aims & Methods: Here, we aimed at investigating the role of the PAI II during AIEC infection. The entire PAI II was deleted and wild-type or the mutated AIEC LF82 strains were used to infect human intestinal epithelial T84 cells. Morphology of AIEC was observed using electron microscopy. AIEC intracellular survival and proliferation were assessed by counting bacterial numbers on Luria Broth (LB) plates. Activation of the transcription factor HIF-1α was assessed by Western blot and by quantifying mRNA expression levels of VEGF, a target gene of HIF-1α. Autophagy was monitored by Western blot for the conversion of LC3-I to LC3-II and by confocal microscopy.

Results: Deletion of PAI II did not alter either morphological aspects (pili, flagella…) or growth of AIEC LF82 bacteria in LB or in T84 cell culture medium. However, loss of PAI II resulted in increases in AIEC intracellular survival and proliferation in T84 cells. This was associated with inhibition of AIEC-induced HIF-1α expression and activation. HIF-1α has been associated with induction of a functional autophagic response. We observed that autophagy was induced in T84 cells infected with wild-type LF82 but not with the mutated LF82. Furthermore, siRNA-mediated HIF-1α silencing in T84 cells inhibited autophagy response, leading to increased intracellular LF82 number, confirming the key role played by HIF-1α in autophagy induction in response to AIEC infection.

Conclusion: Activation of HIF-1α and subsequently autophagy in AIEC-infected cells requires PAI II expression.

Disclosure of Interest: None declared

P0292 MICRORNA-424 MAY REGULATE TRANSCRIPTS IN THE PATHOGENESIS OF INFLAMMATORY BOWEL DISEASES - SUGGESTED MECHANISM

I. Dotan ^1,2, H. Sherman Horev¹, S. Ben-Shachar^2,3

¹IBD Center, Department of Gastroenterology and Liver Diseases, The Research Center for Digestive Tract and Liver Diseases, Tel Aviv Medical Center, ²Sackler Faculty of Medicine, Tel Aviv University, ³Genetic Institute, Tel Aviv Medical Center, Tel Aviv, Israel

Contact E-mail Address: hadassh@tivmc.gov.il

Introduction: Inflammatory bowel diseases (IBD) are associated with differential expression of genes involved in inflammation and tissue remodeling. One mechanism of regulating gene and protein expression is by MicroRNAs (miRs). Recently we performed massive sequencing analysis of ileal biopsies showing that increased expression of multiple miRs occurs in intestinal inflammation, specifically that occurring in ulcerative colitis patients after total proctocolectomy and pouch surgery. miRs expression alterations correlated with disease behavior. Among the miRs with significantly altered expression, miR-424 had a robust increase: 8.4 fold change in Crohn's-like disease of the pouch (CLDP) and 2.6 in normal pouch (NP) compared to the ileum of normal controls (NC). We hypothesized that miRs may have a role in down-regulation of mRNA transcripts in IBD.

Aims & Methods: To define the interaction of candidate miRs with their potential targets and the mechanisms modifying miRs expression in intestinal inflammation. miRs and mRNAs were selected based on our previous microarray studies and in silico data. Levels of mature and primary miR-424 as well as its potential target genes: solute carrier family 6 member 4 (SLC6A4, neurotransmitter transporter) and solute carrier family 36 member 1 (SLC36A1, proton/amino acid symporter) were examined in patients with CLDP and NP as well as in NC and in a human epithelial cell line (HCT-116) incubated with inflammatory cytokines (TNF-α, IL-1β, INF-γ) by quantitative reverse transcription-polymerase chain reaction. Regulation of gene expression by miR-424 was assessed by transfection of specific mimic and miR-424 inhibitor.

Results: miR-424 expression was increased (3.3 fold, p < 0.001), while SLC6A4 mRNA expression was decreased (5.8 fold, p < 0.01) and SLC36A1 expression was lower in ileal biopsies of CLDP patients compared to NC. Primary to mature miR-424 expression ratios were higher in the NP compared to pouchitis (4 fold increase). Similarly, under inflammatory conditions HCT-116 cells expressed 4 fold more miR-424 (p < 0.05) and less SLC6A4 (2.8 fold, p < 0.05) and SLC36A1 (1.3 fold, p < 0.01) compared to untreated cells. Transfection of miR-424 mimic into HCT-116 cells resulted in a decrease in SLC6A4 and SLC36A1 expression (1.3 fold, p < 0.05) whereas transfection of miR-424 inhibitor resulted in an increase in SLC6A4 and SLC36A1 expression (2 fold, p < 0.01 and 1.3 fold, p < 0.05 respectively).

Conclusion: Mature miR-424 expression is increased and its target genes are decreased in intestinal inflammation suggesting its role in gene expression regulation in IBD. The processing of a primary to mature miR is increased in pouch inflammation. As miRs are robustly increased in IBD, the behavior of miR-424 may serve as a proof of concept for the role of miRs in regulating intestinal inflammation in IBD.

Disclosure of Interest: None declared

P0293 FUNGAL MICROBIOTA DYSBIOSIS IN INFLAMMATORY BOWEL DISEASES PATIENTS

H. Sokol¹, V. Leducq², S. Jegou², G. Liguori³, J. Cosnes¹, P. seksik¹, P. Langella⁴, M. L. Richard⁴, L. Beaugerie¹

¹gastroenterology, St Antoine Hospital, APHP, ²Avenir Team U1157, Inserm, paris, France, ³Medical and Surgical Science, University of Bologna, Bologna, Italy, ⁴Micalis, INRA, Jouy en Josas, France

Contact E-mail Address: harry.sokol@aphp.fr

Introduction: The intestinal microbiota plays major roles in human physiology as well as in inflammatory bowel diseases (IBD). It is mostly composed of bacteria, but also contains other microorganisms such as virus and fungi. Although the bacterial part of the gut microbiota is being actively studied, almost no data are available regarding the fungal part. The presence of genes involved in sensing and response to fungi among IBD susceptibility genes and recent results in mouse models suggest a role of the fungal microbiota in IBD pathogenesis. Our aim was to characterize the fungal microbiota in IBD patients.

Aims & Methods: Bacterial and fungal composition of the fecal microbiota of 235 IBD patients and 38 healthy subjects (HS) was determined using 16S (ion torrent) and ITS2 (pyrosequencing) respectively. The obtained sequences were analyzed using the Qiime pipeline to assess composition, alpha and beta diversity. Bacterial and fungal taxa associated with clinical parameters were identified using Multivariate association with Linear Models (MaAsLin) taking into account the following parameters: IBD status, IBD type, disease activity, ileum involvement, gender, age, smoking and treatment (5 ASA, steroids, anti-TNFa, immunosuppressant). Correlation between bacterial and fungal microbiota was investigated using spearman test.

Results: Among the 235 IBD patients (106 in flare, 129 in remission), 149 had Crohn’s disease (CD) and 86 had ulcerative colitis (UC).

The results of the bacterial microbiota analysis were in accordance with published data with notably a decreased biodiversity, a decreased proportion of Firmicutes and an increased proportion of Proteobacteria in IBD patients. Beta diversity analysis showed that samples clustered according to disease activity both for bacterial and fungal microbiota. Fungal microbiota in both IBD patients and HS was dominated by the Basidiomycota and Ascomycota phyla, and by the Saccharomyces, Debaryomyces, Penicillium, and Candida genera. The fungal gut microbiota was found imbalanced in IBD patient with notably an increase Basidiomycota / Ascomycota ratio and a decreased proportion of Saccharomyces and Kluyveromyces compared to HS. The fungal biodiversity was also decreased in IBD patients, particularly in those with colon involvement.

Many correlations were observed between bacterial and fungal genera abundance suggesting an inter-kingdom crosstalk. These correlations were stronger in UC patients compared to CD patients and healthy subjects. Global correlation network was homogenous and even in HS, whereas it was unbalanced and uneven in IBD patients and particularly in UC, suggesting unbalanced crosstalk.

Conclusion: The fungal gut microbiota is dominated by the Basidiomycota and Ascomycota phyla. The fungal microbiota is imbalanced in IBD patients with a reduced biodiversity and an increased Basidiomycota / Ascomycota ratio compared to HS. Correlation analyses suggest an unbalanced crosstalk globally within the microbiota and particularly between fungal and bacterial microbiota components in IBD patients.

Disclosure of Interest: None declared

P0294 ATTENUATION OF DSS-INDUCED COLITIS BY PROBIOTIC ADMINISTRATION IS ASSOCIATED WITH IMMUNOSTIMULATING EFFECTS ON REGULATORY T CELLS

H. Zhang¹, Y. Zhang¹, J. Ma¹, J. Su¹

¹Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

Contact E-mail Address: hjzhang06@163.com

Introduction: The exact etiology of inflammatory bowel disease (IBD) remains unclear, there is much evidence supporting the hypothesis of the involvement of intestinal microbiota in IBD pathogenesis. In recent years, there is increasing interest for using probiotic in IBD. A growing body of evidence suggests that the probiotic bacteria has immune-modulatory ability. So, we investigate the effect of administration of probiotic mixture (bifidobacterium, lactobacillus and enterococcus) on colitis and regulatory T cells in DSS-induced mice.

Aims & Methods: The aim of this study is to investigate the effect of administration of probiotic mixture (bifidobacterium, lactobacillus and enterococcus) on colitis and regulatory T cells in DSS-induced mice.

An acute colitis was induced in BALB/c mice (8-10 week-old) using 3.5% w/v dextrane sulfate sodium (DSS). Mice were randomly divided into five groups: NS group (received saline), DSS group (received DSS), BB group (14-day probiotic mixture without DSS), BD group (received 7-day probiotic mixture prior to DSS administration) and BDB group (14-day probiotic mixture with DSS given at 8th day for 7 days). The Disease Activity Index was monitored daily, colon length and weight were measured and histological scores were evaluated. Regulatory T cells (CD4 + CD25 + Foxp3 + T) in spleen and blood were measured by flow cytometry.

Results: Probiotic mixture administration attenuates the DSS-induced intestinal damage. Compared with DSS group, disease activity Index (DAI) (P <0.001), colonic length (P <0.01), body weight (P < 0.01 in BD group; P=0.075 in BDB group) and histological scores (P <0.001) were significantly improved in mice with probiotic mixture administration. The probiotic mixture protection may be associated with a reduction in CD4 + T cells (total CD4 + T cell in BD group was lower than that of DSS group (P < 0.05)). Intervention with probitic mixture led to a significant increase of regulatory T cell in blood (P < 0.05), but not in spleen.

Conclusion: Administration of probiotic mixture (bifidobacterium, lactobacillus and enterococcus) can reduce intestinal inflammation and damage in DSS-induced colitis.This result was associated with reduction in total CD4 + T cells and increasing regulatory T cells.

Disclosure of Interest: None declared

P0295 THE ROLE OF MIR-19B TARGETING SOCS3 IN MEDIATING INTESTINAL INFLAMMATION

H. Zhang¹, J. Ma¹, J. Su¹, X. Cheng¹

¹Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China

Contact E-mail Address: hjzhang06@163.com

Introduction: The exact etiology of inflammatory bowel disease (IBD) remains unclear. Current evidence suggested that IBD is caused by complex interactions of environmental, genetic, and immuno-regulatory factors. Of these, immune dysregulation is thought to play important roles in the pathogenesis of IBD. Intestinal epithelial cells (IECs) are prominently linked to the pathogenesis of IBD. IECs can attribute to classic inflammatory response. There is accruing evidence that miRNAs play a role in regulating inflammatory processes. Recently, unique miRNA expression profiles have been described in epithelial cells of patients with active IBD. However, the roles of miRNAs in modulating disruption of epithelia during the process of IBD remain incompletely clear.

Aims & Methods: The aim of this study is to investigate whether miR-19b targeting SOCS3 regulate activation of signal transducer and activator of transcription 3 (STAT3) in IECs and mediate intestinal inflammation.

Acute colitis was induced via an intra-rectal injection of TNBS. Levels of SOCS3 and miR-19b in colon tissues from mice were assessed by Western blot (WB) and qRT-PCR. Distribution of miR-19b in intestinal mucosal of CD patients was performed by RNA in situ hybridization (ISH). STAT3 and phosphorylated-STAT3(p-STAT3)in intestinal tissue were determined by immunohistochemical (IHC). CCK8 and flow cytometry were conducted for detection of proliferation ability in HT-29 cells. The expression of cyclinD1 was detected by WB and qRT-PCR after overexpression or knockdown of miR-19b.

Results: Compared with normal control, levels of miR-19b decreased in lesion tissue, while the expressions of SOCS3 protein increased in TNBS-treated mice. The imbalance of miR-19b and SOCS3 in TNBS-induced colitis was similar to that in CD patients. TNBS-induced colitis was improved after intracolonic administration of miR-19b mimic. Using RNA ISH, miR-19b was obviously decreased in intestinal epithelium in CD patients. Expression of p-STAT3 was decreased in CD patients. Overexpression of miR-19b in HT-29 cells downregulated the protein level of SOCS3, but not SOCS3 mRNA. The proportion of cells in phase (S + G2) was increased in HT-29 cells after overexpression of miR-19b. Downregulation of SOCS3 by miR-19b mimic caused phosphorylation of STAT3. Expression of cyclinD1 was induced in cells treated with miR-19b mimic, which was the down stream of STAT3 and associated with cell proliferation and cell cycle.

Conclusion: Intracolonic administration of miR-19b mimic improved colitis in TNBS-induced mice. MiR-19b targeting SOCS3 regulate activation of STAT3 and influence intestinal epetheliul proliferation. This pathway maybe involved in mucosal healing during intestinal inflammatory lesion.

Disclosure of Interest: None declared

P0296 LOW COLECTOMY RATE FIVE YEARS AFTER DIAGNOSIS OF ULCERATIVE COLITIS. RESULTS FROM A PROSPECTIVE POPULATION-BASED COHORT

A. Rönnblom¹, T. Holmström², H. Tanghöj³, U. Karlbom⁴, M. Thörn⁵, D. Sjöberg⁶

¹Dpt of Medical Sciences, Uppsala, Sweden, ²Dpt of Internal Medicine, Dpt of Medical Sciences, Mariehamn, Finland, ³Dpt of Internal Medicine, Eskilstuna, ⁴Dpt of Surgical Sciences, ⁵Dpt of Internal Medicine, Uppsala, ⁶Dpt of Internal Medicine, Falun, Sweden

Contact E-mail Address: anders.ronnblom@akademiska.se

Introduction: The aim of the study was to analyse the first five years of a population based cohort consisting of newly diagnosed patients in all age groups with ulcerative colitis, with respect to medication, surgery and mortality.

Aims & Methods: The patients included in the study were recruited 2005-2009 in the Uppsala Health Care Region (population 642,000) and the cohort has previously been described in detail (1). The average incidence during the study period was 20.0/100 000/year. The mean age for the 526 patients was 39.2 years (median 36.0, IQR 23.0-54.0, range 3-88). The gender distribution male/female was 1.24/1. The medical notes were checked, patients that had moved before five years of observation were contacted by mail for supplementary information.

Results: Of the original 526 patients, two individuals were excluded from further analysis because of uncertain diagnose. Thus the cohort consists of 524 individuals, of whom 495 (87%) could be followed up to 5 years. Nineteen patients (3.6%) had died and two of these could be attributed to IBD (one postoperative death and one colonic cancer). The following drugs were used: 5-ASA (91%), steroids (65%), antimetabolites (28%) and anti-TNF (11%). During the 5-year observation period, 27 patients were subjected to colectomy because of ulcerative colitis, representing 5.7% using Kaplan-Meier survival function. Among patients <17 years at diagnosis (n=42), two were operated (4.8%) during the observation period. A multivariate analysis demonstrated that severity of symptoms at diagnosis was correlated to risk for colectomy (S2 + S3 vs SR OR=15.2 (95% CI 1.87-124.03, p=0.01)). The surgical rate varied according to the various geographical areas of the region (3.0% in the area served by the University Hospital and 11.7% in the surrounding counties).

Conclusion: Five years after diagnosis of ulcerative colitis, 5.7% had been subjected to colectomy. The geographic variation of operative treatment was considerable (3.0-11.7%) due to different approaches to severe episodes of colitis. Mortality caused by ulcerative colitis was low (0.44%)

Disclosure of Interest: None declared

P0297 AFFECTIVE TEMPERAMENT TRAITS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE ASSESSED BY TEMPERAMENT EVALUATION OF MEMPHIS, PISA, PARIS AND SAN DIEGO AUTOQUESTIONNAIRE AND THEIR IMPACT ON QUALITY OF LIFE

A. Mokrowiecka¹, A. Borkowska², E. Malecka-Panas¹

¹Dept of Digestive Tract Diseases, Medical University of Lodz, Lodz, ²Dept of Clinical Neuropsychology, Collegium Medicum, Bydgoszcz, Poland

Contact E-mail Address: annazlo@wp.pl

Introduction: Affective temperaments can be considered as the subclinical manifestation of affective disorders, which have an impact on the clinical course of chronic diseases as inflammatory bowel disease (IBD). Coping abilities of patients are influenced by their personality. Temperament variations may be useful to identify patients at risk and for further introducing the personalized therapy.

Aims & Methods: To explore the effect of affective temperament traits on disease-specific quality of life in patients with ulcerative colitis (UC) and Crohn’s disease (CD).

The study embraces 116 patients with IBD: 61 with UC and 55 – with CD, aged 19-84 years (mean 43 ±7.8), in remission, without serious mental or medical conditions.

The patients completed the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A), which is the assessment for five dimensions of temperament: depressive (TEMPS-A-D), cyclothymic(C), hyperthymic (H), irritable (I) and anxious (A).

For five temperament traits 0-1 scores were calculated. Higher score indicated the higher intensity of affective temperament. Patients Health-Related Quality of Life (HRQL) was assessed with the Inflammatory Bowel Disease Questionnaire

Results: Overall, more than 70% TEPMS-A scores were higher in IBD patients compared to general Polish population. In 25 patients (22%) we found 3 and more affective temperament traits with scores more than 0.5. In 37 patients (33%) at least one score was more than 0.7. The most common combination of affective traits was: depressive, cyclothymic and anxious and these traits reached the highest scores. Irritable temperament score was significantly higher in CD compared to UC patients (p < 0.01).

Mean HRQL in IBD patients were significantly decreased and mean IBDQ scores were 145/ 224. Significant negative correlation was found between HRQL in all IBDQ domains and TEMPS-A traits: D (p < 0.001), C (p < 0.01), I (p < 0.05) and A (p < 0.001).

Conclusion: The results confirmed that affective temperament traits have negative impact on quality of life in IBD patients. Personality traits should be taken into account when using IBDQ in studies as well as in management with IBD patients.

Disclosure of Interest: None declared

P0298 SYMPTOMATIC BURDEN AND EMOTIONAL HEALTH OF SPANISH PATIENTS WITH ULCERATIVE COLITIS. UC-LIFE SURVEY

A. López-Sanromán¹, D. Carpio², X. Calvet³, L. Cea⁴, B. Juliá⁴, C. Romero⁴, F. Argüelles-Arias⁵

¹Hospital Ramón y Cajal, Madrid, ²Complexo Hospitalario Universitario, Pontevedra, ³Corporació Sanitària Universitària Parc Taulí. Sabadell. Departament de Medicina. Universitat Autònoma de Barcelona CIBERehd, Instituto de Salud Carlos III, Barcelona, ⁴Medical Department, Merck Sharp & Dohme de España, Madrid, ⁵Hospital Universitario Virgen Macarena, Sevilla, Spain

Contact E-mail Address: cristina_rdesantos@merck.com

Introduction: ECCO guidelines indicates that psychological factors may have an impact on the course of ulcerative colitis (UC).

Aims & Methods: Here we describe the impact of UC on everyday life and feelings as perceived by patients followed in hospital clinics from Spain. Methods. Thirty-nine gastroenterologists handed each a survey to 15 consecutive patients aged ≥18 years. Patients completed the survey at home and returned it by mail. The emotional impact was evaluated through questions on impact of UC on everyday life, quality of sleep, and feelings (ranked from “never” to “always”).

Results: Response rate was 75% (436/585, mean age 46 years, 53% men). During the past year 51% reported at least one exacerbation and 43% perceived their UC as moderate or severe. For 79% of patients UC prevented them from doing a normal life. The figures were similar regarding age, gender or disease duration. A total of 76% reported UC affected the quality of their sleep, the percentage was higher in women (83% vs 69% in men p=0.001). Those who perceived UC as moderate or severe reported more frequently impact on everyday life and rest than those describing mild disease (92% vs 69%, p < 0.001 and 89% vs 65%, p < 0.001 respectively). The percentage of patients reporting negative feelings due to UC “frequently” or “most of the time” is shown in the table. No differences were found by age ranges. Anxiety and depression were more frequently rated as “frequently” or “most of the time” by women (p < 0.001 and p=0.017 vs men [table]). Those with higher disease burden during past year (with a flare, with perception of moderate/severe UC or with symptoms impacting everyday life), had all the feelings more frequently rated as “frequently” or “most of the time” (p < 0.05, table).

Abstract number: P0298 Table.

Percentage of patients that frequently or always had negative feelings due to ulcerative colitis (n may vary from question to question due to lost answers)

	Unmotivation	Anxiety	Anger	Depression	Frustration	Embarrassment
All (n= 436)	22%	26%	23%	27%	19%	9%
GENDER
Men(n= 229)	20%	19%	21%	25%	20%	7%
Women(n=205)	23%	34%	24%	30%	18%	10%
PERCEPTION OF SEVERITY
Mild (n=227)	15%	18%	15%	19%	15%	7%
Moderate or severe (n=169)	30%	36%	31%	37%	25%	12%
PRESENCE OF FLARE DURING PREVIOUS YEAR
No (n=130)	11%	14%	10%	12%	12%	3%
Yes (n= 252)	24%	30%	27%	34%	22%	11%
SYMPTOMS DURING PREVIOUS YEAR
Symptoms under control (n=185)	12%	16%	11%	17%	9%	4%
Yes, but not affecting my everyday life (n=110)	20%	33%	23%	30%	18%	9%
Yes, affecting my everyday life (n=98)	39%	37%	42%	40%	37%	15%

Conclusion: Data reported by patients underline the noteworthy impact of UC on emotions, everyday life and rest. Patients with higher burden of disease described more frequently such negative emotions. Following ECCO recommendations checking emotional aspects should be part of regular clinical practice.

Acknowledgments. Funded by Merck Sharp & Dohme of Spain and endorsed by ACCU (Spanish association of Crohn’s and ulcerative colitis patients)

Disclosure of Interest: None declared

P0299 ULCERATIVE COLITIS IN THE ELDERLY: A DESCRIPTIVE ANALYSIS OF DISEASE IN THE UK

C. Alexakis¹, V. Chhaya², E. Cecil³, S. Saxena³, R. Pollok²

¹Gastroenterology, St George's, ²Gastroenterology, St George's Hospital, ³Department of Primary Care and Public Health, Imperial College London, London, United Kingdom

Contact E-mail Address: richard.pollok@nhs.net

Introduction: The presence of an ageing population combined with an increase in the incidence of inflammatory bowel disease (IBD) may mean that the burden of elderly-onset ulcerative colitis (UC) will become more apparent. Relatively limited information is available about the disease process in this group. Recent cohort studies from European IBD populations have shed some light on this issue [1,2], but equivalent data for the British population has not yet been described.

Aims & Methods: We aimed to describe demographics, therapies and outcomes in a cohort of British patients with elderly-onset UC (diagnosis confirmed after 60th birthday). Data was sourced from the Clinical Practice Research Datalink (CPRD). This is one of the largest primary care datasets in the UK and has detailed information on diagnoses, clinical events and prescription data for 8% of the British population. Data on disease parameters, medication prescriptions and surgical procedures were collected on individuals aged greater or equal to 60 years with READ codes indicating a diagnosis of ulcerative colitis, over the study period 1990 to 2012. Patients with co-morbid conditions necessitating regular steroid or immunosuppressant therapy were excluded from the final anaylsis.

Results: Over the study period, 4775 patients (52.5% male) with elderly-onset UC were identified, with a mean follow-up of 3.9 years. Mean age at diagnosis was 71.5 years. The proportion of current, non, and ex-smokers were 10.5%, 53.2% and 36.3% respectively. 58.4% of patients had received at least one prescription of 5-aminosalicylate therapy. 46.0% had received a course of oral steroids during follow up with 34.3% prescribed corticosteroid therapy within the first year after diagnosis. 18.1% of patients were classified as steroid dependent (i.e. receiving steroid course > 3 months, or needing a repeat course of steroids within 3 months of finishing the previous course). 8.7% had a prescription for thiopurine (TP) therapy with 4.6% receiving TPs in the first year of diagnosis. 3.9% of elderly onset UC patients underwent colectomy during follow up versus 5.1% in patients aged less than 60 (Fisher's exact test p=0.009). Over half of elderly patients requiring colectomy had surgery within the first year of diagnosis. The table demonstrates multivariate logistic regression of risk factors associated with need for colectomy in elderly patients.

	Odds Ratio	95% Confidence Intervals	p value
Smoking	1.27	0.95-1.70	0.1
5-ASA use	1.12	0.73-1.71	0.51
Thiopurine use	3.77	2.42-5.89	<0.0001
Steroid dependency	2.05	1.35-3.12	0.001

Conclusion: Although colectomy rates appear comparitively lower than in younger populations, suggesting a more benign disease course, there is a concerning level of steroid dependency in this cohort of elderly patients who will be at particular risk from the many side effects of corticosteroid treatment. The low TP use in this group may reflect a less aggressive disease course, but may also indicate cautious prescribing in this age group.

Disclosure of Interest: None declared

P0300 SELF-CONFIDENCE, EMOTIONAL HEALTH AND HEALTH RESOURCES CONSUMPTION AMONG SPANISH PATIENTS WITH ULCERATIVE COLITIS. UC-LIFE SURVEY

D. Carpio¹, F. Argüelles-Arias², X. Calvet³, L. Cea⁴, B. Juliá⁴, C. Romero⁴, A. López-Sanromán⁵

¹Complexo Hospitalario Universitario, Pontevedra, ²Hospital Universitario Virgen Macarena, Sevilla, ³Corporació Sanitària Universitària Parc Taulí. Sabadell. Departament de Medicina. Universitat Autònoma de Barcelona CIBERehd, Instituto de Salud Carlos III, Barcelona, ⁴Medical Department, Merck Sharp & Dohme de España, ⁵Hospital Ramón y Cajal, Madrid, Spain

Contact E-mail Address: cristina.rdesantos@merck.com

Introduction: ECCO guidelines point out that psychological disorders contribute to poorer quality of life (QoL) and to increase the number of doctor visits regardless of disease severity.

Aims & Methods: We describe the prevalence of negative feelings and health resources consumption in UC patients followed in Spanish hospitals. Methods. Thirty-nine gastroenterologists handed a survey to 15 consecutive UC patients aged ≥18 years. Patients completed the survey and returned it by post-mail. The emotional impact of UC was collected by closed questions about feelings (ranked from never to always), and self-confidence. Patients were asked about health resources consumption during the previous year.

Results: Response rate was 75% (436/585, mean age 46 years,53% men). Up to 38% felt that UC reduced their self-confidence. A higher impact of UC on self-confidence was described by older patients (p=0.01), those with longer disease duration (p < 0.001) or higher burden of disease [i.e flares during previous year (p=0.05), perception of UC as moderate or severe (p < 0.001) and presence of symptoms impacting everyday life (p < 0.05)]. The previous year 19%, 31% and 47% respectively reported hospital admissions, emergency room visits or non-scheduled visits. Negative feelings reported by patients are described in the table. Health resources consumption was significantly more frequent among those who scored negative feelings as “sometimes” or “frequently/always” (table).

Abstract number: P0300 Table.

Health resources consumption during previous year. (n varies among questions due to lost answers)

	Hospital Admissions	Emergency room visits	Non-scheduled visits	Steroids use
LACK OF MOTIVATIONNever  (n=119)	6%	14%	27%	28%
Sometimes (n=187)	22%(a)	36%(a)	57%(a)	57%(a)
Frequently/always(n=84)	31%(a)	42%(a)	61%(a)	62%(a)
ANXIETYNever (n=115)	12%	17%	29%	35%
Sometimes (n=174)	18%	30%(a)	54%(a)	49%(a)
Frequently /always (n=102)	27%(a)	50%(a,b)	61%(a)	66%(a,b)
ANGERNever (n=151)	16%	19%	31%	38%
Sometimes (n=145)	17%	38%(a)	58%(a)	52%(a)
Frequently /always (n=87)	25%	40%(a)	65%(a)	64%(a)
DEPRESSIONNever (n=103)	11%	15%	16%	35%
Sometimes (n=184)	18%	30%(a)	48%(a)	48%(a)
Frequently /always (n=106)	30%	50%(a,b)	36%(a,b)	64%(a,b)
FRUSTRATIONNever (n=154)	11%	18%	33%	32%
Sometimes (n=152)	20%(a)	37%(a)	57%(a)	60%(a)
Frequently/always (n=73)	32%(a)	46%(a)	65%(a)	62%(a)
EMBARRASSMENTNever (n=240)	13%	25%	43%	42%
Sometimes (n=107)	25%(a)	39%(a)	57%(a)	55%(a)
Frequently/always (n=33)	36%(a)	52%(a)	64%(a)	73%(a)

(a) P <0.05 vs "Never" ; (b) P <0.05 vs "Sometimes"

Conclusion: In this survey, UC patients reported a significant impact on emotional health and self-confidence. Patients with more frequently negative feelings also described more frequency of health resources consumption.

Acknowledgments. Funded by Merck Sharp & Dohme of Spain and endorsed by ACCU (Spanish association of Crohn’s and ulcerative colitis patients)

Disclosure of Interest: None declared

P0301 SURGERY IN ADULT CROHN’S DISEASE PATIENTS HAS LIMITED IMPACT ON THE MEDICAL AND SOCIAL BURDEN OF DISEASE

D. Schwartz¹, E. Chernin², M. Friger³, O. Sarid⁴, H. Vardi³, D. Greenberg⁵, V. Slonim-Nevo⁴, S. Odes², on behalf of Israel IBD Research Nucleus IIRN

¹Gastroenterology, Soroka Medical Center, ²Gastroenterology, ³Public Health, ⁴Social Work, ⁵Health Systems Management, Ben-Gurion University of The Negev, Beer Sheva, Israel

Contact E-mail Address: doronsh@clalit.org.il

Introduction: Crohn’s disease is a chronic relapsing disease affecting men and woman at their prime, influencing both physical and social aspects of life. We hypothesized that surgery can be perceived as a life event that improves disease perception for the patients and those surrounding them. We investigated this issue in a community cohort of adult Crohn’s patients.

Aims & Methods: Consecutive adult Crohn’s disease patients were recruited from IBD clinics in 5 tertiary hospitals and from our website call, and filled out their demographics, disease status, Harvey-Bradshaw Index (HBI), and the social questionnaires: SF-36 (generic quality of life), and Brief Symptom Inventory (BSI, measures psychological stress). For the analysis parametric and nonparametric statistics were used as required. A logistic multivariate regression model was utilized to examine the associations between surgery as dependent variable with socio-demographic, HBI, BSI and SF-36 variables.

Results: The cohort comprised 518 patients, with mean (± SD) age 40.0 ± 14.8 years. Of these, 156 patients (30.1%) had undergone surgery (CD-S) and 362 (69.9%) not (CD-NS). 38.1% of 189 men underwent surgery versus 25.5% of 329 of women (p < 0.003). Duration of illness was greater in CD-S, 15.9 ± 9.7 years, versus CD-NS, 9.2 ± 7.3 years (p < 0.05), although there was no statistical difference in age between these groups. Smoking status in CD-S (18.4%) and CD-NS (19.8%) was also similar. CD-S patients had more severe present illness than CD-NS as shown by the HBI scores, with 46.8% having HBI > 7 versus 33.9%, respectively (p < 0.001). In the multivariate analysis CD-S was significantly associated with male sex, HBI, and selected components of SF-36 and BSI (Table).

Table.

Results of multivariate analysis for Surgery (CD-S) as dependent variable*

	OR	p
Gender (male)	1.592	0.032
HBI	1.144	<0.001
BSI: somatization	0.589	0.025
BSI: global severity index	1.544	0.088
SF-36: bodily pain	1.016	0.005
SF-36: general health	0.972	<0.001
SF-36: vitality	1.026	<0.001

*Adjusted for age, education, and the other components of BSI and SF-36.

Conclusion: Crohn’s disease patients who underwent surgery were more likely to be males, had evidence of greater disease activity and more psychological stress. They had reduced quality of life with more bodily pain and poorer general health.

Disclosure of Interest: None declared

P0302 COPING STRATEGIES AND DEPRESSION IN CROHN'S DISEASE

F. Furfaro¹, C. Bezzio¹, A. dell'Era¹, S. Carmagnola¹, A. Cassinotti¹, S. Ardizzone¹, R. de Franchis¹, G. Maconi¹

¹Gastroenterology, AO Luigi Sacco Milano, Milano, Italy

Contact E-mail Address: federica.furfaro@alice.it

Introduction: A significant proportion of Crohn's disease (CD) patients shows depressive and anxious disorders. Depression may also lead dysfunctional coping strategies, which implement non-adaptive and often counter-productive behaviours.

Aims & Methods: This study assessed the prevalence of anxious or depressive symptoms, and evaluated the coping strategies in CD patients with severe depressive disorders.

One hundred consecutive CD patients in clinical remission, regularly followed in our IBD Unit were included in the study. Patients with diagnosis of psychiatric disorder preceding the diagnosis of CD and patients with history of substance abuse or neoplastic diseases were excluded.

The eligible patients were screened to identify anxiety and/or depression by using Hospital Anxiety and Depression Scale (HADS). Patients with HADS scores ≥8 in the subscale “depression” were further investigated by means of Cognitive Behavioural Assessment 2.0 and Beck Depression Inventory (BDI). Afterwards the coping strategies were assessed through the Brief-COPE questionnaire.

Results: Thirty-seven patients showed psychiatric co-morbidity: 21 patients had anxious symptoms, and 16 had depressive symptoms with (15 patients) or without (1 patient) anxious symptoms. Seven of these patients (43.8%) showed significant depressive symptoms confirmed at Beck Depression Inventory. None of them had ever been treated for depressive disorder.

Compared to patients without psychiatric disorders, these patients showed lower values of “positive reframing” (p:0.017) that refers to the items “I try to see it in a different light, to make it seem more positive” and “I look for something good in what is happening”; lower values in “planning” (p:0.046) that corresponds to the item “I try to come up with a strategy about what to do”. Conversely, patients with depression showed higher score in “use of instrumental social support” (p < 0.001) corresponding to the items “I talk to someone to find out more about the situation” and “I try to get advice from someone about what to do”, in the “denial” scale (p:0.001) that refers to the items “I say to myself this isn't real” and “I pretend that it hasn't really happened”, and in the “use of emotional social support” (p:0.003) that includes the item “I try to get emotional support from friends or relatives”.

Conclusion: Depressed CD patients have altered coping strategies, meaning that they may not be able to implement functional strategies to manage at best stress related with their disease. These findings confirm that some CD patients may need psychiatric intervention and an interdisciplinary approach between gastroenterologist and psychiatrist.

Disclosure of Interest: None declared

P0303 CRYPTOGENETIC AND CROHN'S PERIANAL FISTULA: WHAT CHANGE IN PSYCHOLOGY OF PATIENTS

F. Furfaro¹, C. Bezzio¹, S. Carmagnola¹, A. dell'Era¹, A. Cassinotti¹, S. Ardizzone¹, R. de Franchis¹, G. Maconi¹

¹Gastroenterology, AO Luigi Sacco Milano, Milano, Italy

Contact E-mail Address: federica.furfaro@alice.it

Introduction: Perianal disease has been recognized as a relevant risk factor for anxiety and depression in Crohn's disease. However, its specific impact on mood disorders in patients with cryptogenic fistula has not been reported so far.

Aims & Methods: The aim of our study was to investigate the prevalence and associations of anxiety and depressive symptoms in the subset of Crohn's patients with perianal fistula and in patients with cryptogenic fistula.

Forty-two adult patients with confirmed diagnosis of Crohn’s disease, in clinical remission, with perianal fistula and 20 patients with cryptogenetic fistulae were included in the study. Patients were included irrespective to the activity of the fistula, whether actively draining or closed, and clinical history of perianal disease, whether previously operated or not.

All patients were investigated using a standard questionnaire assessing demographic and clinical features of disease, and the presence of psychiatric disorders using standardized questionnaires. The questionnaire assessed the development of psychiatric disorders after the diagnosis of perianal fistula, the use of antidepressant or anti-anxiety therapy and current anxiety or depression by means of the Hospital Anxiety and Depression Scale.

Differences in quantitative data were compared using Chi square and Fisher’s exact tests.

Results: Anxiety or depression were reported by 25 (59.5%) patients with Crohn's fistula and by 2 (10%) patients with cryptogenetic fistula (p<.0001).

Fourteen patients (33.3%) with Crohn's fistulae and 18 (90%) of patients with cryptogenetic fistulae had been operated, whilst actively draining fistula were present in 6 Crohn's patients and in 3 patients with cryptogenetic fistulae.

The prevalence of anxiety with or without depression was not significantly correlated with activity of perianal fistulae, but previous operations for perianal fistulae was significantly correlated with anxiety or depression among Crohn's patients (4.1% vs 12.5%; p=0.042)

Conclusion: Perianal fistula is significantly correlated with anxiety, with or without depression, only in Crohn's disease patients. Further studies are required to assess the impact of perianal disease overall quality of life and to address the need to target interventions.

Disclosure of Interest: None declared

P0304 ALCOHOL CONSUMPTION BEHAVIOUR AND IMPACT ON GASTROINTESTINAL SYMPTOMS AMONG SWISS IBD PATIENTS

F. Brunner¹, N. Fournier², R. von Känel³, S. Begré⁴, C. Clair⁵, A. Macpherson¹, P. Juillerat¹

¹Gastroenterology, University Hospital Bern, Bern, ²Institute of Social and Preventive Medicine, University Hospital Lausanne, Lausanne, ³Psychosomatic Medicine, Klinik Barmelweid, Barmelweid, ⁴Psychiatric Clinic Hohenegg, Meilen, ⁵PMU, University Hospital Lausanne, Lausanne, Switzerland

Contact E-mail Address: felix.brunner@insel.ch

Introduction: Little is known about alcohol drinking behaviour and its influence on gastrointestinal symptoms among patients with inflammatory bowel disease (IBD). In a preliminary analysis of the Swiss IBD cohort data using a screening question on alcohol drinking, we estimated a prevalence of 43% (≥ 1x alcohol consumption per week). Moderate alcohol consumption was associated with a shorter disease extend in ulcerative colitis (UC), whereas a lower risk of flares and hospitalizations was observed in Crohn’s disease (CD).

Aims & Methods: We aimed to assess alcohol drinking behaviour and its influence on gastrointestinal symptoms in patients with IBD. Therefore, we sent a questionnaire to patients randomly selected from 3 different groups of patients according to the reported frequency of alcohol consumption at enrolment to the Swiss IBD cohort: Group A (< 1x weekly), B (1-7x weekly) and C (> 1x daily). Data collection was based on demographic variables and disease characteristics from the most recent follow up report available, as well as the average alcohol intake per day (based on standard drinks), type of drinking, the number of days with alcohol consumption per week, influence of alcohol on gastrointestinal symptoms and smoking assessed in a dedicated questionnaire.

Results: We received 383 of 537 (72%) questionnaires from our IBD patients (56% CD and 44%UC): Group A: 182/243 (75%), B: 175/242 (72%), C: 27/52 (52%). The rate of abstainers was similar to the Swiss population*(12%). Among drinkers, 52% drank up to 1x weekly, 29% on 2-3 and 19% on 4-7 days per week. The amount of alcohol on each occasion was 0-20g in 70% of the patients, 20-40g in 24% and 40-60g in 5% and similar for both diseases. The incidence of binge drinking was similar to the Swiss population¹ with 12% monthly (vs. 11.3%), 3% weekly (3.7%) and 1% more than weekly (6%). Binge drinkers (> 6 drinks on one occasion at least monthly) are younger than the other IBD patients (mean age 39 vs. 49 years) and more often smokers (42.4% vs. 25.4%) whereas the amount of standard drinks per week increased with age. After IBD was diagnosed 61% of the patients did not change, 29% reduced, 6% quit or 4% increased alcohol consumption. In both, CD and UC, 30% of patients reported worsening of diarrhea and 15% worsening of abdominal pain and bloating after drinking alcohol. The type of preferred beverage did not significantly influence this changes of symptomatology. Patients did not differ significantly regarding age, disease duration, localisation, behaviour, extraintestinal manifestation and previous surgery in our study population based on alcohol consumption.

Conclusion: Drinking behaviour in Swiss IBD patients is similar to the general population and not influenced by the type of disease. A third of IBD patients reduce or quit drinking after being diagnosed. Worsening of diarrhea, abdominal pain and bloating after drinking alcohol was reported in 15-30% by both UC and CD patients, independently of the type of drinking.

Disclosure of Interest: F. Brunner: None declared, N. Fournier: None declared, R. von Känel: None declared, S. Begré: None declared, C. Clair: None declared, A. Macpherson: None declared, P. Juillerat Lecture fee(s): AbbVie, UCB, MSD and Vifor

P0306 RS2476601 POLYMORPHISM IN PTPN22 IS ASSOCIATED WITH CROHN'S DISEASE BUT NOT WITH ULCERATIVE COLITIS; A META-ANALYSIS OF 16838 CASES AND 13 356 CONTROLS

A. Hedjoudje ^1,2, C. Cheurfa^2,3, C. Briquez¹, A. Zheng⁴, S. Koch¹, L. Vuitton^1,5

¹Gastro-entérologie, Centre hospitalier régional universitaire de Besancon, Besancon, ²Faculté de Médecine, Université Paris Descartes, Paris, ³Anhéstésie réanimation, CHU Charles Nicole, Rouen, France, ⁴Johns Hopkins University Evidence-based Practice Center, Johns Hopkins University, Baltimore, United States, ⁵Gastro-entérologie, Centre hospitalier régional et universitaire, Nancy, France

Contact E-mail Address: abdellah.hedjoudje@gmail.com

Introduction: Although the polymorphism of PTPN22 rs2476601 has been reported to be a susceptibility gene for Crohn's disease, results from different studies varies and remain inconclusive. Also, no association has been found between rs2476601 and the risk of ulcerative colitis. The aim of this meta-analysis is to investigate the association between PTPN22 polymorphism (rs2476601) and the risk of Inflammatory bowel Disease (IBD), Ulcerative Colitis and Crohn's disease.

Aims & Methods: We performed a meta-analysis by two independent reviewers by identifying relevant candidate-gene based studies from EMBASE and PubMed. The Odds ratio (ORs) and 95% confident interval were calculated to estimate the strenght of the associations between rs2476601 and inflammatory bowel disease by using a fixed effect or random effect model meanwhile publication bias was assessed

Results: By pooling the results from 16 different studies, 13 356 controls, 8 182 Crohn's disease, and 8656 Ulcerative Colitis were included. We show that PTPN22 T > C is not associated significantly with a higher risk of developing ulcerative colitis (OR = 1.06 [0.98-1.14], p=0.16) but is associated with a decreased risk of developing Crohn's disease (OR=1.28 [1.17 – 1.40], p < 0.0001). T allele in rs2476601 lower the risk of Crohn's disease by 22%.

Conclusion: This study shows that PTPN22 (rs2476601) is associated with the risk of developing a Crohn's disease significantly but not an ulcerative colitis suggesting different pathways in the pathophysiology of the disease.

Disclosure of Interest: None declared

P0307 A COMPUTATIONAL APPROACH TO GENOTYPE-DRIVEN DRUG REPOSITIONING IN INFLAMMATORY BOWEL DISEASE (IBD)

F. Bonfiglio¹, T. Akhter¹, A. Reznichenko¹, J. Halfvarson², K. Sandberg³, M. B. Hansen³, A. Franke⁴, D. Greco⁵, M. D'Amato¹

¹Karolinska Institutet, Stockholm, ²Örebro University, Örebro, ³Astra Zeneca R&D, Mölndal, Sweden, ⁴Christian-Albrechts-University of Kiel, Kiel, Germany, ⁵Finnish Institute of Occupational Health, Helsinki, Finland

Contact E-mail Address: ferdinando.bonfiglio@ki.se

Introduction: Inflammatory bowel disease (IBD) is a chronic inflammation of the digestive tract, which primarily manifests in two forms, ulcerative colitis (UC) and Crohn's disease (CD). Existing therapies are partly effective, and limited understanding of IBD pathogenesis hampers the development of new therapeutic approaches. Recent applications in computational drug repositioning hold the promise for cost effective solutions.

Aims & Methods: We report an in silico pipeline for genotype-driven drug repositioning in IBD using publicly available data from genome-wide association studies (GWAS), expression quantitative trait loci (eQTL) repositories, and drug-induced gene expression profiles from the Connectivity Map (cMap).

GWAS data were retrieved from ibdgenetics.org, and significant SNPs (p ≤ 0.05) selected at each of the 163 known IBD risk loci. Two expression quantitative trait loci (eQTLs) databases (MuTHER, mRNAbySNP) were screened in order to produce a catalog of IBD genotype-specific eQTLs in different tissues, and to link genetic risk (protection, predisposition) to effect betas (up- or down-regulation). IBD, CD and UC gene expression signatures were then built based on physical distance and consistent cis-effects. These were used for functional annotation with hypergeometric test-based tools (WebGestalt), and as input for cMap drug screening using the embedded algorithm.

Results: We found 900 IBD SNPs associated with eQTLs in 2 databases in 3 different tissues (adipose, skin and/or LCL). After data filtering and quality controls for consistency of eQTL effects across genes, these SNP-eQTL profiles gave rise to IBD- CD- and UC-specific gene expression signatures including 91 annotated genes in total. Gene set enrichment analysis of these signatures highlighted immune response and cytokines production, but also intriguingly blood pressure and sulfur compound metabolism among the involved biological pathways. Similarly, anti-inflammatory compounds were among the top ranking drugs in the cMap screening, but other unexpected high-scoring categories included antipsychotics and antimicrobial. Of note, application of our pipeline to the analysis of available IBD-risk genotypes from individual patients resulted in detectable differences in the output of the corresponding cMap screenings.

Conclusion: We devised a novel computational approach to exploit (risk) genotype and eQTL data for drug repositioning in IBD. While its potential for implementation can greatly increase with the growing number of available tissue-specific eQTL datasets, our study proposes a novel effective translation of genomic information to precision medicine in IBD and other complex diseases.

Disclosure of Interest: None declared

P0308 GENETIC POLYMORPHISM IN THE TLR4 RELATED GENE CAN BE A PREDICTIVE FACTOR OF LONG-TERM EFFECT OF INFLIXIMAB TREATMENT FOR CROHN’S DISEASE

K. Matsushima¹, H. Isomoto¹, T. Ishida², T. Inamine³, S. Urabe¹, R. Uehara¹, T. Honda¹, H. Minami¹, H. Machida¹, Y. Akazawa¹, C. C. Chen¹, N. Yamaguchi¹, K. Ohnita¹, F. Takeshima¹, H. Hamada⁴, K. Nakao¹, K. Tsukamoto³

¹Gastroenterology and Hepatology, Nagasaki University, Nagasaki, ²Oita Red Cross Hospital, Oita, ³Department of Pharmacotherapeutics, Nagasaki University, ⁴Medical Education Development Center, Nagasaki University Hospital, Nagasaki, Japan

Contact E-mail Address: matsu7281978@yahoo.co.jp

Introduction: Infliximab (IFX) is a chimeric anti-tumor necrosis factor-α (TNF-α) monoclonal antibody exerting therapeutic effects against Crohn's disease (CD). However, some primary failure patients have been unable to achieve remission at the short-term period of 10 weeks. Moreover, the some responders at 10 weeks did get remission at the long-term period of 1 year later. Therefore, identification of biomarkers that might predict IFX therapeutic effects is important.

Aims & Methods: The purpose of this study was to investigate whether polymorphisms of target genes in the TLR4 signaling pathway are associated with the therapeutic effects of IFX for CD patients, and whether such polymorphisms could be used as new genetic biomarkers to identify CD patients having the sensitivity or resistance to IFX for the short- or long-term treatment.

The study subjects were 127 unrelated CD patients treated with IFX in our Hospitals between 2012 and 2013. Patients were classified into two groups, responders and non-responders, based on the presence of IFX effect at 10 weeks and 1 year after IFX administration. We examined a candidate gene-based association of 29 single nucleotide polymorphisms of 8 target genes in the TLR4 signaling pathway with the therapeutic effects of IFX, using the allele, minor allele dominant, and minor allele recessive models.

Results: The genetic analyses indicated that the frequency of a C/T or T/T genotype of rs4251580 in IRAK4 in the minor allele dominant model were significantly decreased in responders as compared to non-responders for the middle-term treatment of 1 year (P = 0.014, odds ratio (OR) = 0.289), implicating ∼3.5-fold resistance to IFX. Conversely, a C/C genotype of rs4251580 indicated ∼3.5-fold sensitivity to IFX. Likewise, the possession of a T/T genotype of rs7255265 in TICAM1 indicated ∼4-fold resistance to IFX at 1-year treatment period (P = 0.038, OR = 0.252). Conversely, a C/C or C/T genotype of rs7255265 showed ∼4-fold sensitivity to IFX. Subsequently, we carried out a genetic test with a combination of the two genetic factors (IRAK4 and TICAM1 genotypes), indicating that the possession of both the C/C genotype of rs4251580 in IRAK4 and the C/C or C/T genotype of rs7255265 in TICAM1 strongly showed responsiveness to IFX (P = 0.003, OR = 4.44). The sensitivity and specificity of this genetic test were estimated at 72.2% and 63.2%, respectively.

Conclusion: This is the first report that IRAK4 and TICAM1 could be associated with the responsiveness to IFX in CD patients. Combination of the 2 SNPs in rs4251580 and rs7255265 could be a biomarker to predict therapeutic effects at 1 year after IFX administration as well as target molecules for new therapeutic drugs overcoming the resistance to IFX. These results suggested that certain genetic prediction in the TLR4 signaling pathway and its downstream associated molecules might be involved in IFX responsiveness, possibly through altered expression of pro-inflammatory cytokines that would be held in common between the TNF-α and TLR4 signaling and the downstream cascades.

Disclosure of Interest: None declared

P0309 THE CLINICAL RELEVANCE OF THE IBD-ASSOCIATED VARIATION WITHIN THE RISK GENE LOCUS ENCODING PROTEIN TYROSINE PHOSPHATASE NON-RECEPTOR TYPE 2 IN PATIENTS OF THE SWISS IBD COHORT

M. R. Spalinger¹, M. Vögelin¹, J. Zeitz¹, L. Biedermann¹, J.-B. Rossel², M. C. Sulz¹³, P. Frei¹, S. Scharl¹, S. R. Vavricka¹, M. Fried¹, G. Rogler¹, M. Scharl⁴, on behalf of Swiss IBD Cohort Study Group

¹University Hospital Zürich, Zürich, ²Centre Hospitalier Universitaire Vaudois, Lausanne, ³Kantonsspital St. Gallen, St. Gallen, ⁴Division of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland

Introduction: The gene locus encoding protein tyrosine phosphatase non-receptor type 2 (PTPTN2) has been associated with an increased risk of developing inflammatory bowel disease (IBD). We have previously shown that PTPN2 plays a critical role in maintaining intestinal epithelial barrier function, cytokine secretion and autophagy. The single nucleotide polymorphism (SNP) rs1893217 within the PTPN2 gene locus results in a dysfunctional PTPN2 protein and is associated with Crohn’s disease (CD). SNP rs1893217 is in perfect linkage disequilibrium with the CD- and ulcerative colitis (UC)-associated PTPN2 SNP rs2542151. Here, we studied the association of PTPN2 SNP rs1893217 and clinical characteristics of the affected IBD patients.

Aims & Methods: 1,073 patients with CD and 770 patients with UC or indeterminate colitis (IC) from the Swiss IBD Cohort Study (SIBDCS) were included. Epidemiologic, disease and treatment characteristics were analysed for an association with the presence of one of the rs1893217 isoforms ‘homozygous wild-type’ (TT), ‘heterozygous’ (CT) and ‘homozygous variant’ (CC).

Results: 2.88% of IBD patients were identified with CC, 26.8% with CT and 70.4% with TT genotype. In univariate logistic regression analysis the CC-genotype was associated with an early age of diagnosis (OR 1.315; 95% CI: 1.068-1.620; p=0.010) and existence of bilestones (OR 4.793; 95% CI: 2.000-11.490; p < 0.001) in CD patients as well as with the presence of pancolitis (OR: 4.581; 95% CI: 1.267-16.556; p=0.020) in UC patients. These factors remained significant in the subsequent multiple regression analysis. Presence of the C-allele was associated with the presence of uveitis (OR: 2.020; 95% CI: 1.201-3.398; p=0.008), but protected from aphtous oral ulcers (OR: 0.578; 95% CI: 0.335-0.998; p=0.049) in CD patients. UC/IC patients carrying the C-allele were diagnosed at younger age (OR: 1.122, 95% CI: 1.001-1.257; p=0.049) and required intestinal surgery more frequently (OR: 3.056, 95% CI: 1.011-9.239; p=0.048). Significance was seen both in univariate as well as multiple regression analyses. Both, presence of the CC genotype or the C-allele were associated with a better response to treatment with anti-TNF antibodies in both CD and UC patients (chi-square test, p-value: 0.050).

Conclusion: IBD patients carrying the C-allele of PTPN2 SNP rs1893217 are at greater risk for developing a severe disease course as indicated by younger age at diagnosis, pancolitis and higher frequency of surgeries, but are more likely to respond to treatment with anti-TNF antibodies. These findings indicate a clinical relevance of this PTPN2 risk variant in IBD patients and suggest that PTPN2 may be used as predictive marker for early treatment with anti-TNF antibodies.

Disclosure of Interest: None declared

P0310 SNP RS6105269, A NEW PROGNOSIS MARKERS FOR CROHN DISEASE

P. Aguilar-Melero¹, J. M. Benitez¹, E. Iglesias¹, R. Medina Medina¹, I. Salgueiro¹, M. L. Garcia¹, V. Garcia-Sánchez¹

¹IMIBIC/Hospital Universitario Reina Sofía, Córdoba, Spain

Contact E-mail Address: p.aguilar.melero@gmail.com

Introduction: Crohn disease (CD) is a chronic disease that can have a variable course, from a mild inflammatory effect to a severe disease with the appearance of fistulas, ulcers, abscesses, strictures that can lead to a significant impairment in quality of life. An early identification of these patients, would allow an early intensive treatment for changing the natural history of the disease. For this purpose, is essential to identify prognosis markers. The SNP rs6105269 has been identified as risk factor for CD [1].

Aims & Methods: The aim of the study is to analyze the rs6105269 polymorphism, located in the MACROD2 gene, as a prognosis marker of CD and the effect of the polymorphism in the protein expression of MACROD2. 95 patients have been enrolled and classified according to their genotype of rs6105269 polymorphism (AA, AG and GG). A Chi-square test or Fisher test have been used to study if there are significant differences among the genotypes in clinical characteristics related to a severe CD. We propose a definition of severe/disabling disease based on the development of non reversible tissue lesions as any colectomy or at least two small bowel resections or a unique resection >50 cm or complex perianal fistulizing disease. Furthermore, plasma levels of MACROD2 protein have been analysed by ELISA assay.

Results: 43% of AA patients has family history of IBD (GG 12%, AG 9%, p=0.009). The AA genotype is link to a stricturing and fistulizing patterns (AA 80% patients, GG 47% and 38% AG, p=0.02) and 73% of patients with AA genotype develops a severe/disabling CD vs AG + GG 44%, (p= 0.04). 50% of AA patients suffers from a complex perianal disease vs 12% of GG or 19% of AG (p= 0.01). In particular, suprasphincteric, transsphicteric and extrasphicteric fistulas are present in 36% of AA patients vs 10% of AG + GG patients (p=0.03) and 31% of AA patients have required surgical drainage of fistula abscess vs 9% of GG and 2% of AG (p= 0.01). Furthermore, the levels of the inflammatory marker CRP were increased in AA patients (AA: 22.5 ng/ml, GG: 3.8 ng/ml, AG: 4.2 ng/ml, p=0.02), while the MACROD2 plasma levels are significantly downregulated in genotype AA (AA: 851 ng/ml, GG: 1372 ng/ml, AG: 907 ng/ml, p=0.04).

Conclusion: Genotype AA of the polymorphism rs6105269 is associated with a more severe CD and the polymorphism can be used as a prognosis marker of the disabling disease. Genotype AA produces a downregulation in protein levels of MACROD2, suggesting that this protein may have a protective role in CD.

Disclosure of Interest: None declared

P0311 MR ENTEROGRAPHY OR CAPSULE ENDOSCOPY - WHAT DO CROHN'S DISEASE PATIENTS PREFER?

A. Lahat¹, M. M. Amitai², S. Neuman¹, N. Levhar¹, D. Yablecovitch¹, U. Kopylov¹, S. Ben-Horin¹, R. Eliakim¹

¹Gastroenterology, ²Radiology, Chaim Sheba Medical Center, Ramat Gan, Israel

Contact E-mail Address: zokadi@gmail.com

Introduction: Despite differences in the information obtained by capsule endoscopy (CE) and magnetic resonance enterography (MRE) regarding mucosal and intestinal wall abnormalities in Crohn's disease patients, one of these modalities may need to be chosen or may suffice when evaluating disease activity. There are no data on patients' preference that would help guide the choice between these two modalities in these instances. Despite differences in the information obtained by capsule endoscopy (CE) and magnetic resonance enterography (MRE) regarding mucosal and intestinal wall abnormalities in Crohn's disease patients, one of these modalities may need to be chosen or may suffice when evaluating disease activity. There are no data on patients' preference that would help guide the choice between these two modalities in these instances.

Aims & Methods

Aim: To compare patients' tolerance to MRE vs CE.

Methods: Patients with known small bowel CD in clinical remission (CDAI < 150) or with mild symptoms (CDAI < 220) were prospectively recruited and underwent video capsule endoscopy after verification of small bowel patency and MRE examination. Patients' were asked to fill a questionnaire addressing specific points regarding inconvenience during preparation, during procedure and post procedure. Side effects and procedure preference were addressed. Degree of severity was graded from 1 (not at all) to 5 (severe). Questionnaires were included for analysis only when more than 95% of the items were addressed.

Results: Out of 62 patients approached 56 fulfilled inclusion criteria. Results are summarized in table 1.

subject	MRE (severity degree± SD)	CE (severity degree± SD)	P value
home preparation	2.38 ± 1.32	1.13 ± 2.68	0.1215
pre-exam discomfort	1.22 ± 2.7	0.99 ± 1.5	<0.0001
discomfort during the exam	1.22 ± 3.7	1.08 ± 2.0	<0.0001
nausea	18. 1 ± 2.24	0.53 ± 1.29	<0.0001
vomiting	1.05 ± 1.5	0.37 ± 1.07	0.009
bloating	1.14 ± 2.01	0.55 ± 1.25	0.0002
Abdominal pain	1.1 ± 2.24	0.63 ± 1.33	<0.0001
tenesmus	0.87 ± 1.40	0.55 ± 1.14	<0.0001
claustrophobia	0.7 ± 1.40	0 ± 1	<0.0001
Time consuming	1.19 ± 3.46	1.23 ± 3.0	0.0594
Difficulty	1.13 ± 3.42	0.98 ± 2.03	<0.0001
Drinking of contrast material	1.22 ± 3.2	NR	NR

44 patients (78%) preferred to repeat CE.

Conclusion: CE was significantly better tolerated in most parameters and preferred by 78% of patients . The superior tolerability of CE should be considered when choosing between these two modalities for suitable patients.

Disclosure of Interest: A. Lahat Financial support for research: The study was sponsored by the Helmsley Charitable Trust., M. Amitai Financial support for research: The study was sponsored by the Helmsley Charitable Trust., S. Neuman Financial support for research: The study was sponsored by the Helmsley Charitable Trust., N. Levhar Financial support for research: The study was sponsored by the Helmsley Charitable Trust., D. Yablecovitch Financial support for research: The study was sponsored by the Helmsley Charitable Trust., U. Kopylov Financial support for research: The study was sponsored by the Helmsley Charitable Trust., S. Ben-Horin Financial support for research: The study was sponsored by the Helmsley Charitable Trust., R. Eliakim Financial support for research: The study was sponsored by the Helmsley Charitable Trust.

P0312 EVALUATION OF NT-PROBNP IN INFLAMMATORY BOWEL DISEASE

A. Wacrenier¹, A.-M. bourgeois¹, J. Ausseil¹, C. Szymanski¹, H. Thiebault¹, F. Brazier¹, A. Galmiche¹, E. Nguyen-khac¹, J.-L. Dupas¹, J.-F. Colombel², M. Fumery¹

¹Amiens University Hospital, Amiens, ²Icahn School of Medicine At Mount Sinai, New-York, France

Contact E-mail Address: mathurinfumery@gmail.com

Introduction: N-Terminal pro-Brain Natriuretic peptide (NT-proBNP) is currently used as a diagnostic marker in heart failure. Elevated NT-proBNP and significant correlation between NT-proBNP and CRP was recently reported in rheumatoid arthritis (1) and in Crohn’s Disease (CD) (2). The purpose of this study was to evaluate NT-proBNPas a marker of inflammatory bowel disease (IBD) activity.

Aims & Methods: In this single-center study, NTproBNP assay was performed in patients with CD or ulcerative colitis (UC), irritable bowel syndrome (IBS) and in healthy controls. Clinical characteristics (Harvey-Bradshaw score (HB), Mayo Clinic score (Mayo)), biological (CRP) and endoscopic (CDEIS, UCEIS) data were collected at the time of NTproBNP dosage. Echocardiography was performed in case of NT-proBNPserum levels> 124pg/ml.

Results: To date, 118 patients with CD, 26 with UC, 20 with IBS and 18 healthy controls were included. The median serum NT-proBNP was 50.5 pg/ml [Q1=28-Q3=94] in CD group, 72 pg/ml [46-138] in the UC group, 43.5 pg/ml [27-111] in IBS Group and 34.5pg/ml [26-49] in the control group. A significant increase of NT-proBNPlevels was observed in CD patients with HB > 4 (p=0.02) or UC with Mayo > 2 (p=0.03) as compared to inactive patients. There was a significant correlation between NTproBNP and, the HB score (r=0.31, p=0.0005), and the Mayo score (r=0.45, p=0.01) respectively. A significant increase in NT-proBNP was observed in CD (p < 0.001) and UC (p < 0.0016) patients having CRP > 10 mg/l as compared to patients with CRP£10. There was a significant correlation between NT-proBNP and CRP in both CD (r=0.64, p < 0.001) and UC (r=0.8, p < 0.001). Among the 34 patients who had a colonoscopy a significant correlation between NT-proBNP and, CDEIS (r=0.85, p < 0.001), and UCEIS (r=0.78, p=0.007) was observed respectively. ANTproBNP level of 57pg/ml had a sensitivity (Se) of 70% and a specificity (Sp) of 63% (AUC 0.73, 95%CI [0.63-0.83]) to predict a CRP > 10 mg/l in CD. In UC, a rate of NTproBNP of 75 pg/ml had a Se of 88% and a Sp of 75% (AUC 0.87, 95%CI [0.71-1]) to predict a CRP > 10 mg/l. All echocardiograms performed were normal.

Conclusion: NT-proBNP is correlated to the clinical, biological and endoscopic activity of CD and UC and may be a new biomarker in IBD.

Disclosure of Interest: None declared

P0313 RELEVANCE OF ULTRASONOGRAPHIC PARAMETERS IN PREDICTING INFLAMMATORY BOWEL DISEASE IN A PEDIATRIC POPULATION

A. Dell'era¹², D. Dilillo³⁴, E. Galli⁴, F. Meneghin³⁵, F. Furfaro¹², C. Bezzio¹², F. Penagini³⁴, C. Mantegazza³⁴, F. Scrignoli³⁴, G. V. Zuccotti³⁴, G. Maconi¹²

¹Gastroenterology Unit - Ospedale L. Sacco di Milano, ²Department of Biomedical and Clinical Sciences - Università degli Studi di Milano, ³Department of Paediatrics, Università degli Studi, ⁴Ospedale dei Bambini V. Buzzi, ⁵Department of Pediatrics - Ospedale L. Sacco, Milano, Italy

Contact E-mail Address: alessandra.dellera@unimi.it

Introduction: Bowel ultrasound (B-US) has been widely recognized as a useful examination in patients with suspected IBD owing to its lack of invasiveness. The relevance of increased bowel wall thickening (BWT) and the additional value of other US parameters (e.g. lymph node enlargement and mesenteric hypertrophy (MH)), in the diagnosis of IBD have not been investigated so far.

Aims & Methods: This study aims at investigating the diagnostic accuracy of several US parameters in detecting IBDs in a pediatric population.

All patients aged 2-18 years referred to the Pediatric Gastroenterology Clinic of our Hospital since 2007 to 2013 for recurrent abdominal pain and/or altered bowel habits were retrospectively considered. Patients presenting with known organic diseases or already investigated with digestive endoscopy were excluded; those with a full US report (including altered US bowel pattern (US-BP), BWT, MH, pathologic lymph nodes, free abdominal fluid, presence of stenosis, abscesses or fistulae) were considered eligible. Ileocolonoscopy, performed in patients with a high index of suspicion of IBD, on the basis of paediatrician’s assessment and biochemical test results (e.g. calprotectin, CRP), has been used as reference standard. Children who initially were not selected for endoscopy, were followed for at least one year for the appearance of possible additional symptoms.

Results: 113 patients (mean age 10.8 years [range 2.1- 17.7], 65 male) were enrolled. 23 IBD (20.4%; 8 ulcerative colitis, 12 Crohn’s disease and 3 indeterminate colitis) were diagnosed. Among the bowel US variables considered, only US-BP, MH and BWT > 3 mm were found useful to identify IBD on univariate binary logistic analysis. On multivariate analysis, these factors were independent predictors of IBD, even after adjustment for age and sex: US-BP (OR 9.8;95%CI 1.6-59.0); MH (OR 5.2;95%CI 1.1-25.1) and BWT > 3 mm (OR 5.4;95%CI 0.7-40.1). Diagnostic accuracy of single US parameters and their combination, in distinguish between IBD and non IBD patients, is reported in the table.

Abstract number: P0313

Variables	Se, % (95% CI)	Sp, % (95% CI)	PPV, % (95% CI)	NPV, % (95% CI)
Altered US-BP	78.3 (69.3-85.2)	93.3 (86.6-96.9)	75.0 (65.8-82.5)	94.4 (87.9-97.6)
Mesenteric hypertrophy	65.2 (55.6-73.8)	92.2 (85.2-96.2)	68.2 (58.7-76.4)	91.2 (84.0-95.5)
BWT > 3 mm	69.6 (60.1-77.7)	96.7 (90.9-99.0)	84.2 (75.9-90.1)	92.6 (85.6-96.4)
BWT > 3 mm + US-BP + MH	56.5 (46.9-65.7)	100 (95.9-100)	100 (95.9-100)	90.0 (82.6-94.6)
BWT > 3 mm or US-BP or MH	82.6 (74.1-88.9)	86.7 (78.7-92.1)	61.3 (51.6-70.2)	95.1 (88.9-98.1)

Conclusion: Among several US parameters suggestive of IBD, only the increased BWT, MH and altered echopattern are independent predictors of IBD and useful in distinguishing IBD from non-IBD patients. Owing to their high specificity and NPV, these parameters can be useful in identifying patients who do not need diagnostic invasive procedures in the short time.

Disclosure of Interest: None declared

P0314 ACCURACY OF FECAL CALPROTECTIN, BOWEL ULTRASONOGRAPHY AND INFLAMMATORY INDEXES IN THE DIAGNOSIS OF PAEDIATRIC INFLAMMATORY BOWEL DISEASE

A. Dell'Era¹², D. Dilillo³⁴, E. Galli³⁴, F. Meneghin⁴⁵, C. Bezzio¹², F. Furfaro¹², F. Penagini³⁴, C. Mantegazza³⁴, F. Scrignoli³⁴, G. V. Zuccotti³⁴, G. Maconi¹²

¹Gastroenterology Unit - Ospedale L. Sacco, ²Department of Biomedical and Clinical Sciences - Università degli Studi di Milano, ³Ospedale dei Bambini V. Buzzi, ⁴Department of Paediatrics, Università degli Studi di Milano, ⁵Department of Pediatrics - Ospedale L. Sacco, Milano, Italy

Contact E-mail Address: alessandra.dellera@unimi.it

Introduction: IBD in pediatric age may present with non specific gastrointestinal symptoms overlapping with functional bowel disorders or with extraintestinal manifestations making the diagnosis a challenge.

Aims & Methods: The aim of our study was to assess the accuracy of non invasive parameters including fecal calprotectin (FC), bowel ultrasound wall thickening (BWT) and blood inflammatory indexes (BII) alone or in combination as a diagnostic tool for paediatric inflammatory bowel disease (IBD).

Subjects aged 2-18 years referred to our paediatric gastroenterology clinic from 2007 to 2013 for recurrent abdominal pain and/or altered bowel habits were retrospectively considered. Subjects who underwent laboratory tests (FC, BII: white blood cell count [WBC], C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]) and bowel ultrasound as initial assessment were eligible. Exclusion criteria were: signs or symptoms highly suggestive for IBD (perianal disease or haematochezia), known organic disease, previously performed endoscopy. Eligible patients were followed-up for one year.

Results: Seventy-seven patients (mean age 11.3, 44 males) were retrospectively included. One-year diagnoses were: 23 (29.9%) IBD (8 ulcerative colitis, 12 Crohn’s disease 3 indeterminate colitis), 54 (70.1%) non-IBD diseases. Mean values of WBC, CRP, ESR (p < 0.001) and at least one BII pathological value were higher in IBD vs non-IBD patients (65.2% v 11.1%, p < 0.001). Pathological BWT (> 3 mm) and FC (> 200 μg/g) were more frequent in IBD than in non-IBD patients (69.6% vs 3.7%, p < 0.001 and 95.7% vs 27.8%, p < 0.001 respectively). Considering 3 (BII + FC + BWT) or 2 parameters together (FC + BWT, FC + BII) IBD patients had more simultaneous pathological results than non IBD-patients (52.2% vs 0%, p < 0.001; 69.6% vs 0%, p < 0.001; 65.2% vs 3.7%, p < 0.001 respectively). Diagnostic accuracy of considered parameters are described in the table.

Variables	Se, % (95% CI)	Sp, % (95% CI)	PPV, % (95% CI)	NPV, % (95% CI)
BII*	65.2 (53.3 – 75.6)	88.5 (78.5 – 94.4)	71.4 (59.7 – 81.0)	85.2 (74.7 – 92.0)
BWT(> 3 mm)	69.6 (57.9 – 79.3)	96.3 (88.5 – 99.1)	88.9 (79.2 – 94.6)	88.1 (78.3 – 94.6)
FC (> 200 µg/g)	95.6 (87.7 – 98.8)	72.2 (60.7 – 81.5)	59.5 (47.7 – 70.3)	97.5 (90.2 – 99.6)
FC + BWT + BII	52.2 (31.8 – 72.6)	52.2 (40.6 – 63.6)	100 (94.1 – 100)	83.1 (72.4 – 90.3)
FC + BWT	69.6 (57.9 – 79.3)	100 (94.1 – 100)	100 (94.1 – 100)	88.5 (78.7 – 94.3)
FC + BII	65.2 (48.5 – 79.1)	88.2 (73.3 – 95.7)	88.2 (73.3 – 95.7)	65.2 (48.5 – 79.1)

Se = sensitivity. Sp= specificity, PPV= positive predictive values, NPV= negative predictive values.* at least one altered

Conclusion: In initial work-up for IBD, FC alone presents highest sensitivity but poor specificity. The combination of FC + BWT presents the highest accuracy in identification of patients needing further invasive procedures in the short term.

Disclosure of Interest: None declared

P0315 DIFFERENTIAL EXPRESSION OF MICRORNAS IN SERA AND FECES OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE

A. Link¹, K. Schoenauen¹, N. Le¹, U. von Arnim¹, C. Schulz¹, P. Malfertheiner¹

¹Gastroenterology, Hepatology and Infectious Diseases, OTTO-VON-Guericke University Hospital Magdeburg, Magdeburg, Germany

Contact E-mail Address: alinkmail@gmail.com

Introduction: Assessment of the disease activity in inflammatory bowel disease (IBD) is essential for appropriate treatment management. Symptom-based disease activity scores do not always correlate with endoscopic scores and are not reliable for verification of mucosal healing as a primary treatment goal. New non-invasive molecular biomarkers could substantially simplify the treatment management. MicroRNAs (miRNAs) are functionally active molecules and the expression pattern is frequently deregulated during inflammation and carcinogenesis.

Aims & Methods: Here, we evaluate the potential of several circulating and fecal miRNAs as diagnostic biomarkers for IBD. In the proof-of-principle trial, we obtained blood or fecal specimens form patients with known or newly diagnosed IBD. From total 61 patients, 41 had histologically confirmed Crohn´s Disease (CD) or indeterminate colitis and 18 patients ulcerative colitis (UC). Among them 38 patients had an active disease and 24 were in remission (CDAI < 150 for CD or Mayo-Score ≤ 1 for UC). Total RNA was isolated from sera and fecal specimens and quantitative RT-PCR analyses was performed for miR-16, miR-21, miR-223 and miR-155 using TaqMan Assay.

Results: The sera samples from IBD patients showed an increased expression level of miR-21 (p < 0.0001) and miR-223 (p < 0.0001), but not miR-155, compared to controls. The expression was higher in patients with clinically active disease compared to those in remission. In subgroup analyses, patients with CD demonstrated highest miRNA expression for both miRNAs compared to controls and UC (p < 0.0001, Kruskal-Wallis test). Similarly, miRNAs in feces from IBD patients showed strong increase in expression of all four miRNAs with highest expression of miR-16, miR-223 and miR-155. Opposite to miRNA expression in sera, stool samples from UC showed similarly or even higher miR-16, miR-223 and miR-155 level in feces. Clinical remission in IBD patients was associated with normalization of fecal miRNA expression. Despite the significant correlation with disease activity, only fecal miRNA, but not circulating miRNAs, correlated with surrogate parameters such as fecal calprotectin or C-reactive protein.

Conclusion: Our data provide a novel evidence for differential expression of miRNAs in sera and feces from patients with IBD. The increased expression of miRNAs correlates with disease activity especially in fecal samples. Further studies are needed to optimize this miRNA-based biomarker tool and evaluate the clinical applicability for treatment monitoring in IBD patients.

Disclosure of Interest: None declared

P0316 UROCORTIN 1 IN COLONIC MUCOSA IN PATIENTS WITH ULCERATIVE COLITIS

A. A. Ghweil¹, U. A. morsy²

¹Tropical Medicine and Gastroenterology, Qena Faculty of Medicine Egypt, Qena, ²internal medicine, sohag faculty of medicine, sohag, Egypt

Contact E-mail Address: alimena1@yahoo.com

Introduction: Ulcerative colitis (UC) is characterized by a long-standing chronic inflammation of the bowel with intermittent periods of exacerbation and remission. Its acute exacerbation appears to be related to various stresses. Urocortin 1 (Ucn1) may play important roles in integrated local responses to stress. We therefore examined local production of Ucn1 in patients with UC by immunohistochemistry

Aims & Methods: We therefore examined local production of Ucn1 in patients with UC by immunohistochemistry to detect the degree of inflammation. Ucn1 immunoreactivity was predominantly detected in lamina propria plasma cells and enterochromaffin cells. In UC patients without glucocorticoid treatment, Ucn1-positive cells and plasma cells increased in proportion to the severity of inflammation.

Results: Ucn1 immunoreactivity was predominantly detected in lamina propria plasma cells and enterochromaffin cells. In UC patients without glucocorticoid treatment, Ucn1-positive cells and plasma cells increased in proportion to the severity of inflammation (P < 0.0001). Ucn1-positive cells significantly increased in UC patients with advanced inflammatory grades, compared with a control group (P < 0.0001) and nonspecific colitis group (P < 0.0001). In glucocorticoid-treated patients, Ucn1-positive cells were significantly lower in number, compared with the nonglucocorticoid-treated group.

Conclusion: The present study showed that Ucn1-positive cells were correlated with the severity of inflammation in colonic mucosa with UC, and glucocorticoid treatment decreased these cells. Ucn1 therefore may act as a possible local immune-inflammatory mediator in UC.

Disclosure of Interest: None declared

P0317 USE OF FAECAL CALPROTECTIN PATHWAY IN PRIMARY CARE TO DISTINGUISH IRRITABLE BOWEL SYNDROME FROM INFLAMMATORY BOWEL DISEASE

A. Dhaliwal¹, J. ORourke¹, V. Sagar¹, J. Burdsall¹, R. Ransford¹, A. Milestone¹

¹Gastroenterology, Hereford County Hospital, Hereford, United Kingdom

Contact E-mail Address: adhaliwal85@gmail.com

Introduction: Faecal Calprotectin (FCP) testing is a simple, non-invasive investigation which can differentiate Inflammatory Bowel Disease (IBD) from Irritable Bowel Syndrome (IBS). It has high negative predictive values which allow utilisation in Primary Care by reducing unnecessary referrals to secondary care & expensive/invasive diagnostic tests eg. Colonoscopy and in turn suggest potential cost-effective benefits. FC is well established in secondary care, but the literature for FC in primary care is extremely limited.

Aims & Methods

Aim: Evaluation of a pilot study of a defined FC pathway in Primary Care.

Method: A primary care referral pathway was devised to guide appropriate use of FC in Primary Care to exclude IBD in appropriate patients, particularly if secondary care referral was being considered.

A pathway proforma with initial screening tests (FBC, LFTs, TTG, CRP, TSH & stool microbiology). Inclusion/Exclusion criteria: 16-45yrs age, IBS-compatible symptoms for ≥6 weeks/recurrent, no red flags. This was based on IBS guidelines (BSG), FC literature & recent NHS Centre for Evidence-Based Purchasing report (2010).

FC results (via Quantum Blue test kits) were classified as normal, intermediate or high. Each result was advised on further appropriate action. Subsequent clinic attendances, investigations, diagnostic outcomes & associated costs were evaluated.

Results: Nineteen GP surgeries (19/22) referred 277 patients via FC pathway over 24 months (Jan 2013-Jan 2015). Forty-five samples rejected as inappropriate.

Table 1.

Faecal Calprotectin results (received to date)

FCP Interpretation	FCP result (μg/g)	Patients (n=232)	Pathway Action
Normal <50	<50	62.1% (144/232)	IBD excluded.  Retain in primary care
Indeterminate	50-150	22.4% (52/232)	Repeat after 4-6 weeks,  if repeat > 50ug/g refer  to secondary care
Elevated	>150	15.5% (36/232)	Refer to secondary care

Diagnosis outcomes were available on 175/232 patients at the time of presented data analysis: Elevated 13.7%(24),Indeterminate 19.4%(34) & Normal 66.8%(117).

In Elevated FC clinic attenders, IBD was detected in 50%(11/22).

Indeterminates were repeated in only 68%: normal repeat 52.2% (12/23), 2 IBD cases detected. After a normal FC, 12.8% were referred to secondary care anyway, but no IBD detected.

In the normal FC group alone, assuming a normal FCP avoided a secondary care referral in 87.2% (102/117), the potential cost savings =£73,468 (assuming new patient clinic + 1 colonoscopy=£741.68).

Conclusion: Preliminary data suggests a structured FC pathway is effective in distinguishing IBD & IBS in Primary Care with significant cost savings. Further refinement is required for age ranges & FC cut-off points. Based on this pilot data & latest NICE Diagnostic Appraisal 11, the local Clinical Commission Group have commissioned a secondary care supervised FC service for primary care.

Disclosure of Interest: None declared

P0318 ILEAL CROHN'S DISEASE: MAGNETIC RESONANCE ENTEROGRAPHY AS A PREDICTOR OF RELAPSE AFTER ANTI-TNF DISCONTINUATION

J. C. Gallego¹, A. Echarri², A. Porta¹, S. E. Bencheikh¹, V. Ollero², J. Castro²

¹Radiology, ²Gastroenterology, Complexo Hospitalario Universitario de Ferrol, Ferrol, Spain

Contact E-mail Address: josecarlos.gallego.ojea@sergas.es

Introduction: Anti-TNF therapy has proven effective in maintaining remission of Crohn's disease (CD), although the optimum duration and strategies for withdrawal in asymptomatic patients remain unclear. The discontinuation of anti-TNF may be considered due to safety and cost issues and decision should be based on clinical, endoscopic, and biological factors. However, in cases of ileal CD, ileocolonoscopy study is limited and biomarkers such as C-reactive protein (CRP) or calprotectin may be less useful in evaluating inflammatory activity.

A multidiscliplinary european expert panel (EPACT-II update) considered imaging techniques to show an “uncertain” suitability for monitoring CD activity, so that there have been few studies about their role in the decision of stopping biologicals.

Aims & Methods: The aim of this study is to evaluate the capability of MR-enterography to predict disease relapse after withdrawal of anti-TNF therapy in patients with ileal CD.

A prospective study was conducted between 2009 and 2014 in our hospital over CD patients with ileal involvement in whom anti-TNF (Infliximab or Adalimumab) was stopped. Withdrawal was only carried out in patients on deep clinical, biochemical, and endoscopic remission, defined as absence of symptoms (Harvey-Bradshaw score ≤ 3), endoscopic mucosal healing (SES-CD <2), and CRP < 5 mg/L or Calprotectin <150 µg/g. Follow-up visits were performed every 3 months after cessation of treatment or earlier in cases of suspected relapse.

Patients underwent a Magnetic Resonance Enterography (MRE) before drug withdrawal on a Philips Intera 1.0 scan (median 30 days, range 10-82). The degree of activity of the ileal CD was assessed by an MRE score used in our hospital.

The MRE scores of the patients with and without relapse were compared using the independent samples t-test. Furthermore, a logistic regression analysis of the total MRE score as well as each parameter individually was performed, considering the relapse as the independent variable.

Results: A total of 29 patients (16 females and 13 males) with a mean age of 36.6 years (range 16-64) were included in the study. The median follow-up time since biological withdrawal was 45.2 months (range 15-72). The average time of recurrence was 17.1 months (range 3-57). Relapse rates were 24% at 1 year and 52% at 2 years.

Patients who relapsed had higher MRE score (4.2 vs. 2.5 p< 0.02) than those who did not. The relative risk of relapse in patients with an MR score > 3 was 2.21 (1.1-5 p<0.05), significantly higher than in patients with a score of 0-3 in the pre-withdrawal MRE.

Logistic regression analysis showed that MRE score is an independent predictor of relapse (hazard ratio 0.185 p=0.02). In terms of single MR parameters, only the presence of hyperintensity on T2-weighted sequences, which translates the bowel wall oedema, can be regarded as an independent predictor of relapse (hazard ratio 0.149 p<0.04).

Conclusion: This study demonstrates that, at least in patients with ileal CD, MRE should be taken into consideration when deciding the withdrawal of anti-TNF therapy in patients who are in clinical, biological, and endoscopic remission.

A MRE score >3 as well as the hyperintensity of the bowel wall on T2-weighted sequences increase the likelihood of relapse.

Disclosure of Interest: None declared

P0319 RELATIONSHIP BETWEEN ANTI-TNF TROUGH LEVEL THRESHOLDS AND EFFICACY LEVEL IN LUMINAL AND PERIANAL CROHN´S DISEASE: DIFFERENT STRATEGIES IN CLINICAL PRACTICE

A. Echarri¹, R. Ferreiro², R. Fraga¹, J. Cid³, M. Barreiro de Acosta², S. Pereira⁴, D. Carpio⁵, L. de Castro⁴, S. Soto⁶, A. Fernández-Villaverde⁷, V. Ollero¹, J. Gallego⁸, B. Gonzalez⁹, E. Castro¹⁰, J. Cadilla⁴, on behalf of EIGA group

¹Gastroenterology, Complejo Hospitalario de Ferrol, Ferrol, ²Gastroenterology, Complejo Hospitalario de Santiago, Santiago, ³Inmunology, Complejo Hospitalario de Coruña, La Coruña, ⁴Gastroenterology, Complejo Hospitalario Vigo, Vigo, ⁵Gastroenterology, Complejo Hospitalario Pontevedra, Pontevedra, ⁶Gastroenterology, Complejo Hospitalario Orense, Orense, ⁷Gastroenterology, Povisa, Vigo, ⁸Radiology, Complejo Hospitalario de Ferrol, Ferrol, ⁹Gastroenterology, Complejo Hospitalario de Coruña, La Coruña, ¹⁰Gastroenterology, Complejo Hospitalario Lugo, Lugo, Spain

Contact E-mail Address: ana.echarri.piudo@sergas.es

Introduction: Several studies have shown a correlation between antiTNF trough levels (TL) and clinical or endoscopical remission in luminal Crohn´s disease (CD), but there are few data about the role of TL in perianal CD or in radiological response.

Aims & Methods: Our aim was to determine the optimal TL associated with clinical, endoscopical and radiological remission for different phenotypes of CD. We included 32 antiTNF naïve patients with moderate to severe luminal (n=24) and perianal (n=8) CD under antiTNF treatment over 24m. Management of patients was based on clinical assessment and investigators were blinded to the TL results.

The TL measurements were performed just before antiTNF injection simultaneously with faecal calprotectin (calprotectin < 250ug/g was defined as normal). The Harvey-Bradshaw and the Perianal Disease Activity Index (PDAI) were reported (HBI-remission < 4; PDAI-remission < 3). Endoscopic evaluation was performed at weeks 0 and 54 (SES-CD remission < 2). In case of ileal location or perianal disease, magnetic resonance enterography (MRE) or pelvic resonance were performed. The activity was assessed with our own validated MRE index (remission < 3) and the Van Assche Index for perianal disease.

Results: At 54w, 84% of patients were in clinical remission. Deep remission (clinical with endoscopical /radiological remission) was observed in 56.2%. Up to 37% of all patients required dose escalation due to a loss of response in the first year (62% of perianal CD vs 21.8% of luminal CD;p < 0.05). Intensification was effective in 75% of cases in whom serum TL after escalation was detected above cut-off levels. Patients in clinical remission without endoscopical or radiological remission showed calprotectin >250 ug/g in 84%.

The optimal IFX /ADA TL cut-off associated with clinical remission in luminal CD was 1.1μg/ml and 2.51μg/ml respectively (sensitivity: 78% and 82%; specificity: 76% and 78%), while IFX /ADA TL cut-off associated with normal calprotectin, endoscopical or radiological remission in luminal disease was 2.7μg/ml and 5.4 μg/ml (sensitivity: 79% and 74%; specificity: 76% and 80%). The optimal IFX /ADA TL cut-off in perianal disease was similar for clinical, endoscopical and radiological remission: 2.7μg/ml and 5.4 μg/ml respectively (sensitivity: 79% and 74%; specificity: 76% and 80%). IFX TL > 2.7 and ADA TL > 5.4 were associated with a decreased risk of treatment failure (RR 0.34; RR 0.38).

Conclusion: 1. Serum anti-TNF TL associated to endoscopical or radiological remission are higher than TL associated to clínical remission in luminal Crohn´s disease, but not in perianal disease where cut-off levels are the same in both clinical and radiological remission. Furthermore, perianal CD required dose escalation more frequently than luminal CD.

2. A calprotectin level > 250ug/g was associated with endoscopical or radiological activity in patients on clinical remission and could be useful to decide upon the need of endoscopical /radiological explorations.

Disclosure of Interest: None declared

P0320 USABILITY STUDY OF A SMARTPHONE-BASED CALPROTECTIN HOME TEST

A. Beyer¹, C. Reinhard², J. Weber², F. Perretta², H. Vogelsang¹

¹AKH - Med. Universität Wien, Vienna, Austria, ²BÜHLMANN Laboratories AG, Schönenbuch, Switzerland

Contact E-mail Address: cre@buhlmannlabs.ch

Introduction: Inflammatory Bowel Disease (IBD) is a chronic inflammation of the gut presenting with phases of active inflammation, remission and relapses. IBD treatment goals are mucosal healing and persistent remission. Calprotectin measured in patients’ stool samples is a well-established biomarker to measure the inflammatory activity in the gut. Periodical assessment of calprotectin levels is important to measure effectiveness of the treatment as well as predicting relapses. Until now this meant that patients send in their stool sample for laboratory analysis, leading to long time spans between sample collection and final test result. To ensure real-time information about the inflammatory activities in the gut for both, the patient and the clinician, we have developed a calprotectin home test called IBDoc^®. The IBDoc^® consists of a stool collection and extraction device (CALEX^® Valve) and an immunochromatographic calprotectin rapid test, which is measured using a smartphone App (CalApp^®) controlling the phone’s camera. Once the test is measured the result is sent to a webserver (IBDoc^® Portal) allowing the treating physician immediate access to the result.

Aims & Methods: The objective of this study was to evaluate the usability of the IBDoc^® calprotectin home test system with patients in respect of handling both, the physical test components as well as the integrated software.

10 voluntary patients suffering from IBD and naïve to the IBDoc^® system were trained to perform the test by their IBD nurse. The patients were then asked to perform a calprotectin stool test every two weeks over a period of two months by themselves at home using the IBDoc^® system. The patients were asked to fill in a questionnaire after the first and the last test performed. The questionnaires were based on 5-point Likert scale questions concerning all steps of the test in respect of usability aspects. It also contained free commentary sections and system usability scale (SUS) score question. The SUS is commonly used for measuring and comparing the usability of software and integrated software systems.

Results: All patients were able to able to perform home test using the IBDoc^® system during the course of the test period. All patients (100%) felt well instructed and the instructions for the test were well understood (4.7 on a 5-point Likert Scale). When asked how easy it was to measure the test cassette with the smartphone, the patients judged this question with an average score of 4.8 on a 5-point Likert scale. The test result was displayed by the smartphone app in a clear way with a traffic light interpretation and quantitative results within the measuring range of 30-1000 µg/g of calprotectin. The test result was easy to understand for all patients (100%). All patients would use the IBDoc^® system in the future (100%). 87% of the patients felt that the home test helps them in their disease management. The IBDoc^® system reached a mean SUS score of 88 on a scale from 0 to 100. This SUS is well above the software industry’s average score of 68.

Conclusion: This study shows that calprotectin home testing using a smartphone as measuring system was well accepted among IBD Patients. The complexity of the application is low, the entire IBDoc^® system can be considered very user-friendly and is easy to handle by lay users without prior knowledge or experience of immunochromatographic rapid tests.

Disclosure of Interest: None declared

P0321 SELECTING IBD PATIENTS WHO WILL BENEFIT FROM THROMBOPROPHYLAXIS THROUGH A RISK ASSESSMENT THAT INCLUDES CLOT LYSIS PARAMETERS AND CLINICAL ASSESSMENT

L. Bollen¹, N. Vande Casteele¹, W. Van Moerkercke², G. Van Assche², M. Ferrante², S. Vermeire², A. Gils¹

¹KU Leuven, ²University Hospitals Leuven, Leuven, Belgium

Contact E-mail Address: ann.gils@pharm.kuleuven.be

Introduction: Patients with inflammatory bowel disease (IBD) have a higher risk of developing thromboembolic events (TE) compared to the healthy population. TE has a substantial impact on mortality in IBD and TE prevention requires improved awareness and management.

Aims & Methods: The aim of the study is to describe the clinical characteristics of IBD patients with a history of TE and to compare markers of clot lysis between (1) IBD patients and healthy controls (HC) and (2) IBD patients with (IBD + TE) and without a history of TE (IBD-TE).

In this study, 84 IBD patients in whom a TE occurred (between January 1987 and March 2014) after the diagnosis of IBD, seen at an academic referral center between February 2009 and May 2012 were included. During the same period, 118 IBD patients without a history of TE and 113 healthy controls were selected as control groups in this case-control study. Three clot lysis parameters (area under the curve (AUC); 50% clot lysis time (CLT) and amplitude) were determined.

Results: Of the 84 IBD + TE patients (63% Crohn’s disease, 44% males), 70/84 (83%) developed a venous TE and 25/84 (30%) patients were identified with recurrent TE. At time of TE, 60/84 (71%) patients had active disease and 36% received steroids. Within a 6-month period preceding the TE, 31/84 (37%) had been operated of whom only 17% received thromboprophylaxis at hospital discharge. Both the 50% CLT and AUC were significantly associated with the presence of IBD as compared to controls. Moreover, AUC (31 (24-49) vs. 22 (13-31), p < 0.05), 50% CLT (110 (64-132) vs. 95 (70-126) minutes, p < 0.05) and amplitude (0.295 (0.222-0.436) vs. 0.241 (0.168-0.308), p < 0.05) were significantly higher in IBD + TE vs. IBD-TE and remained higher after adjustment for age, gender, C-reactive protein, type of disease, presence of comorbidities and disease activity.

Conclusion: This study reveals that IBD patients have an altered clot lysis profile compared to healthy controls. In addition, the clot lysis parameters differ significantly between IBD patients with and without a history of TE. Of the IBD patients with a history of TE, 36% received steroids at time of TE and 37% underwent recent surgery of whom only a minority received thromboprophylaxis at hospital discharge. To date, IBD patients with a high risk for TE are given thromboprophylaxis. However, for the patients with low to moderate risk for TE it is less clear who will benefit from prophylactic therapy. Therefore, we propose to perform a risk assessment in which clot lysis parameters and IBD specific risk factors for TE are combined to identify the patients who can benefit from prophylactic therapy with low molecular weight heparins.

Disclosure of Interest: L. Bollen: None declared, N. Vande Casteele: None declared, W. Van Moerkercke: None declared, G. Van Assche Financial support for research: MSD, Abbvie, Lecture fee(s): MSD, Abbvie, Takeda, Ferring, Consultancy: MSD, Abbvie, Takeda, Ferring, Genetech/Roch, Pfizer,, M. Ferrante Lecture fee(s): Takeda, Abbvie, Janssen, MSD, Chiesi, Tillots, Zeira, Consultancy: Takeda, Abbvie, Janssen, MSD, Boehringer-Ingelheim, Ferring, S. Vermeire Financial support for research: MSD, Abbvie, Lecture fee(s): MSD, Abbvie, Takeda, Falk, Tillotts, Consultancy: MSD, Abbvie, Takeda, Falk, Ferring, Shire, Galapagos, Hospira, Mundipharma, Genetech/Roch, Pfizer, Celgene, A. Gils Financial support for research: Grant FWO-Vlaanderen G.0464.10

P0322 VITAMIN D STATUS IN IBD PATIENTS: A COMPARISON OF THREE DIFFERENT ASSAYS

A. Krajcovicova¹, T. Hlavaty¹, Z. Leskova¹, Z. Kubinova¹, M. Huorka¹, J. Payer¹

¹5th Internal Medicine Department, Faculty of Medicine Comenius University and University Hospital Bratislava, Slovakia, Bratislava, Slovakia

Contact E-mail Address: krajann@hotmail.com

Introduction: Vitamin D (VD) is a fat soluble secosterol that is produced in the skin after the sun exposure. Epidemiological studies show significant associations of VD deficiency and immune mediated diseases. The plasma 25-OH vitamin D3 concentration is a reliable biomarker for VD status but assays' variability makes adequate monitoring of VD difficult.

Aims & Methods: The aim of this study was to compare three different assays for measurement of 25(OH)D and to evaluate the impact of 25(OH)D assessment on clinical decision making.

Blood samples from 50 IBD patients were evaluated in a blinded way in three different laboratories using diverse assays of 25 (OH) vitamin D monitoring such as high-performance liquid chromatography (HPLC), IDS automated immunoassay (IDS) and competitive binding assay (CBP). We correlated the VD levels of different assays using Pearson correlation coefficient. To quantify the agreement between total 25(OH)D serum levels from all three assays, the interclass correlation coefficient (ICC) was calculated. We evaluated the clinical accuracy of each assay by examining the agreement of assays in sorting patients into distinct categories according to difference of VD levels using the cutoffs (< 5ng/ml) for acceptable agreement, (5-10ng/ml) significantly different and (>10ng/ml) insufficient.

Results: The median serum 25(OH)D level measured by CBP was 17.9ng/ml (range 3.0 to 39.3ng/ml), by HPLC 27.3ng/ml (range 4.6 to 53.2ng/ml) and by IDS 24.4ng/ml (range 9.0 to 48.0ng/ml). The linear correlation between different assays was Pearson r=0.69 for HPLC and RIA, 0.69 for HPLC and CBP, 0.63 for RIA and CBP. Comparing 25(OH)D assay HPLC with CBP gave the best agreement with an ICC 0.23 (95% CI -0.06, 0.481; p=0.058). We saw total disagreement between assays IDS and CBP with an ICC= 0.02 (95% CI -0.258, 0.299; p=0.439). To a lesser extent, we saw a disagreement between IDS and HPLC with an ICC= -0.22 (95% CI -0.476, 0.067; p=0.063). By sorting individual patients samples into distinct categories according to the difference of 25(OH)D levels, we have seen the best agreement between the HPLC and IDS (64%, 29/48). Total discordance in 24% (12/50) patients was found comparing CBP and IDS. When applying the cut-off 30ng/ml for defining optimal level of 25(OH)D, the HPLC and IDS classifies 31.25% (15/48) and 26% (13/50) of patients as normal, respectively. CBP with 16% (8/50) underestimates the number of individuals having 25(OH)D concentrations above 30ng/ml.

Conclusion: The linear correlation between different assays was 0.63-0.69. We have seen a clinically significant difference between measured 25(OH)D values in 18.8-24% samples.

Disclosure of Interest: None declared

P0323 PREVALENCE AND CAUSES OF ANAEMIA IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES IN SOUTHERN ITALY

A. Testa¹, A. Rispo¹, M. Romano², M. Patturelli³, G. Pellino⁴, M. E. Bottiglieri⁵, M. Martorano⁶, M. Diaferia¹, A. G. Gravina⁶, G. Riegler³, F. Selvaggi⁴, N. Caporaso¹, F. Castiglione¹

¹Department of Clinical Medicine and Surgery, University “Federico II” of Naples, ²Department of Clinical and Experimental Medicine “Magrassi-Lanzara”, ³Gastroenterology Unit, ⁴Surgery, Second University of Naples, napoli, ⁵Hospital of Marcianise, Caserta, ⁶Hospital of Sapri, Sapri, Italy

Contact E-mail Address: annatesta82@virgilio.it

Introduction: Anaemia (AN) is frequently associated with inflammatory bowel diseases (IBD) with a prevalence varying from 17% to 68%. In recent years, the management of AN in IBD has became a major issue as it negatively affects both the underlying disease and the quality of life of affected patients.

Aims & Methods:

Aim: To evaluate the prevalence and causes of AN in patients with IBD living in a region of Southern Italy.

Methods: We prospectively performed a one-year multicentre study in Campania (Italy) including all consecutive IBD cases attending 5 Units. AN was defined in presence of haemoglobin values Hb <13 g/dl for males and Hb <12 g/dl for females; severe AN was defined in case of Hb <10 g/dl. To explore the causes of AN, all anaemic patients underwent a second-line haematological assessment including ferritin, transferrin, vitamin B12, folic acid and homocysteine levels and screening for celiac disease (total IgA and anti-transglutaminase antibodies). Furthermore, in all IBD cases CRP and ESR were evaluated. Iron deficiency AN (IDA) was diagnosed in case of ferritin <30 ng/ml and transferrin saturation (TSAT) <16%. AN of chronic disease (ACD) was diagnosed when elevated CRP/ESR values coexisted with TSAT <16% and ferritin >100 ng/ml; mixed type AN was considered in case of TSAT <16% and 30 ng/ml < ferritin < 100 ng/ml.

Results: The study population included 965 IBD patients (582 CD; 383 UC) of whom 142 in- and 823 out-patients. AN was diagnosed in 134 out 965 IBD patients (14%). No significant difference was seen between CD and UC groups (81 CD vs 53 UC; 13.9% vs 13.8%; p=n.s.). The prevalence of AN was more frequent in the admitted IBD group (26% in- vs 11.7% out-patients; p < 0.01; O.R. 2.2) and in patients with active disease (CD: 34% active vs 16% in remission; p < 0.01; OR 2.1 – UC: 26% active vs 19% in remission; p=0.03; O.R. 1.3). Furthermore, AN appeared to be more frequent in patients with ileo-colic CD and in those with extensive UC (p < 0.01). Regarding the causes of AN, IDA was present in 72 patients (53.7%), ACD in 12 patients (8.2%), 11 patients (8.2%) had mixed type AN, 9 had thalassemia (6.7%), 8 (5.9%) had macrocytic AN, while in 18 patients (13.4%) the causes remained unclassifiable. Vitamin B12 deficiency was observed in 7.4% of CD patients and in no case of UC. Folic acid deficiency was detected in 6.1% of CD and in none of the patients with UC. There was no evidence of celiac disease.

Conclusion: AN is common among patients with IBD in Southern Italy and is more frequent in IBD patients with active and extensive disease and in whom needing hospitalization. Iron deficiency still remains the major cause of AN in IBD population.

Disclosure of Interest: None declared

P0324 DEFINITIONS OF THE ENDOSCOPIC LESIONS IN CROHN'S DISEASE: REPRODUCIBILITY STUDY AND GETAID EXPERT CONSENSUS

A. Buisson¹, J. Filippi², A. Amiot³, G. Cadiot⁴, M. Allez⁵, P. Marteau⁵, Y. Bouhnik⁵, G. Pineton de Chambrun⁶, A.-L. Pelletier⁵, S. Nancey⁷, D. Moussata⁸, A. Attar⁵, A. Blain⁹, L. Vuitton¹⁰, G. Vernier-Massouille¹¹, P. Seksik⁵, M. Nachury¹², J.-L. Dupas¹³, L. Peyrin-Biroulet¹⁴, J.-Y. Mary⁵, E. Louis¹⁵

¹Clermont-ferrand, ²Nice, ³Créteil, ⁴Reims, ⁵Paris, ⁶Montpellier, ⁷Lyon, ⁸Tours, ⁹IMM, Paris, ¹⁰Besançon, ¹¹Tourcoing, ¹²Lille, ¹³Amiens, ¹⁴Nancy, France, ¹⁵Liège, Belgium

Contact E-mail Address: a_buisson@hotmail.fr

Introduction: Emergence of mucosal healing as therapeutic goal in Crohn's disease (CD) has highlighted the need for endoscopic scores. Although other scores are available, the CD Endoscopic Index of Severity (CDEIS) [1] remains, to date, the most validated score to assess the severity of CD endoscopic lesions. Clarifying the definition of the endoscopic lesions composing this score appeared as a keypoint to optimize the CDEIS use.

Aims & Methods: This expert consensus was performed according to a Delphi-like method (12 experts) to define aphtoid erosions (AE), superficial ulcerations (SU), deep ulcerations (DU), stenosis and fistulas. These consensual definitions were then submitted to 30 other IBD physicians from the GETAID to determine an independent acceptance rate (AR). For the intra and inter-observer variation studies, 100 short films were selected (study leader), focusing on AE, SU, DU or a sham lesion (≈25% for each lesion). Overall 15 GETAID members (not the study leader) read independently the 100 films, indicating the recognized lesion. A re-reading of the same 100 films in a randomized order by the same readers was organized one month later using the same methodology. For the intra-observer variation study, the standard κ-coefficient was used from repeated readings of each observer to measure the agreement level on defining endoscopic lesions. For the inter-observer variation study, the κ-coefficient was estimated as described by Fleiss for nominal agreement among many observers.

Results: AE was defined as an ulceration with a white center whose diameter is < 5 mm with red halo (AR=29/30). DU was defined as a frank depression compared to the surrounding mucosa OR striated bottom of the ulceration OR mucosal detachments OR well-like ulcerations (AR=24/29). SU was defined as an ulceration whose features fit neither with that of AE nor with that of DU, as previously defined (AR=24/29). Stenosis was defined as a narrowing of the intestinal lumen making impossible or difficult to pass with an adult colonoscope (AR=25/29). Fistula was defined as a deep and well-limited hole whose bottom cannot be seen, with leaking faecal or purulent material OR with a suspected communication with another organ (AR=27/29).

Intra and inter-observer agreements (κ-values)

	AE	SU	DU	sham lesions
Intraobserver estimate range	0.419-0.843	0.572-0.891	0.502-0.934	0.289-0.805
Interobserver estimate ± sd	0.554 ± 0.03	0.548 ± 0.04	0.693 ± 0.04	0.569 ± 0.03

IBD experience duration, mean endoscopies number for IBD for the last 3 years and the participation to the definition process, did not influence intra-observer agreement.

Conclusion: The definitions of CD endoscopic lesions retrieved from this GETAID expert panel, showing substantial reproducibility, should improve the standardization and the use of the CDEIS in the era of mucosal healing.

Disclosure of Interest: None declared

P0325 DIFFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING IS EFFECTIVE TO DETECT ILEOCOLONIC ULCERATIONS IN CROHN'S DISEASE

A. Buisson¹², C. Hordonneau³, M. Goutte¹², R. Hilaire², L. Boyer³, B. Pereira⁴, G. Bommelaer²

¹Microbes, Intestine, Inflammation and Susceptibility of the Host, UMR 1071 Inserm/Université d'Auvergne; USC-INRA 2018, ²Gastroenterology department, ³Radiology department, University Hospital Estaing, ⁴DRCI, Biostatistics Unit, University Hospital, Clermont-Ferrand, France

Contact E-mail Address: a_buisson@hotmail.fr

Introduction: Magnetic resonance entero-colonography (MREC) enables accurate assessment of ileocolonic Crohn’s disease, but the need for bowel cleansing and rectal enema limits considerably its use in daily practice. Diffusion-weighted MREC (DW-MREC), with no bowel cleansing and no rectal enema, is highly accurate in assessing inflammation in ileal CD using the Clermont score (=1.646 × bowel thickness − 1.321 × ADC + 5.613 × edema +8.306 × ulceration + 5.039) as it is highly correlated to the Magnetic Resonance Index of Activity (MaRIA) and the simplified endoscopic score for CD (SES-CD)[1-3]. DW-MREC highly assess CD colonic inflammation using apparent diffusion coefficient (ADC), the quantitative parameter of DW-MREC, compared to the MaRIA [3]. However the ADC performances in colonic CD compared to endoscopy remain unknown.

Aims & Methods: We evaluated DW-MREC accuracy to assess endoscopic activity. Overall, 44 CD patients underwent prospectively and consecutively DW-MREC and colonoscopy within 4 weeks (mean interval=17 ± 11 days). Apparent diffusion coefficient (ADC) and Clermont score were calculated from DW-MREC. The colonoscopies were scored using CDEIS and SES-CD. Radiologists were blinded from endoscopic findings and endoscopists were blinded from radiologic findings.

Results: Mean ADC was moderately correlated with total CDEIS (rhô=−0.40; p=0.0067) and total SES-CD (rhô=−0.33; p=0.032).

Considering the 194 segments, ADC was moderately correlated with segmental CDEIS (rhô=−0.48; p < 0.001) and segmental SES-CD (rhô=−0.44; p < 0.001). ADC values were lower in segments with deep ulcers (1.30 ± 0.23) or superficial ulcerations (1.75 ± 0.64) than in non-ulcerated segments (2.15 ± 0.5)(p=0.001). Using a receiver operating curve, we determined that segmental ADC < 1.42 detected endoscopic deep ulcerations with sensitivity (se)=0.91 and specificity (spe)=0.83 (AUC=0.84; p < 0.001). Segmental ADC < 1.88 detected endoscopic superficial ulcerations with se=0.64 and spe=0.75. The segmental ADC values decreased when the ulcerations size increased(p < 0.001).

Considering ileal segments (n=36), Clermont score was correlated with ileal CDEIS (rhô=0.63;p < 0.05) and ileal SES-CD (rhô=0.58;p < 0.05). Clermont score was higher in ulcerated segments (23.3 ± 8.4) than in non-ulcerated segments (12.4 ± 10.0)(p=0.006) and increased with ulceration size (p=0.012). Clermont score > 18.9 detected ulcerations with se=0.79 and spe=0.73.

Among the 44 CD patients, while 10 (22.7%) were in endoscopic remission (no ulceration and no endoscopic stenosis), 8 (18.2%) were in DW-MRI remission (no segmental ADC <1.88 AND no Clermont score ≥18.9 AND no MRI stenosis). The DW-MRI remission detected endoscopic remission with high Spe and NPV (90.9% and 85.7%, respectively).

Conclusion: DW-MREC using ADC and Clermont score is effective to indirectly detect endoscopic ulcerations in ileocolonic Crohn’s disease.

Disclosure of Interest: None declared

P0326 ENDOSCOPIC FACTORS INFLUENCING FECAL CALPROTECTIN VALUE IN CROHN’S DISEASE

F. Goutorbe¹, M. Goutte¹², R. Minet-Quinard³, A.-L. Boucher¹, B. Pereira⁴, G. Bommelaer¹, A. Buisson¹²

¹Gastroenterology department, University Hospital Estaing, ²Microbes, Intestine, Inflammation and Susceptibility of the Host, UMR 1071 Inserm/Université d'Auvergne; USC-INRA 2018, ³Biochemistry laboratory, University Hospital Estaing, ⁴DRCI, Biostatistics Unit, GM Clermont-Ferrand University and Medical Center,, Clermont-Ferrand, France

Contact E-mail Address: a_buisson@hotmail.fr

Introduction: Fecal calprotectin is usually an accurate biomarker of Crohn’s disease (CD) endoscopic activity. Identifying the endoscopic situations in which fecal calprotectin is less reliable remains unexplored. We aimed to determine the endoscopic factors influencing fecal calprotectin level in CD.

Aims & Methods: Overall, 53 CD patients underwent consecutively and prospectively colonoscopy, with CD Endoscopic Index of Severity (CDEIS) calculation and stool collection. Fecal calprotectin was measured using quantitative immunochromatographic test. To calculate the overall affected or ulcerated surfaces, we considered that each segment (according to CDEIS) represented 20% of the overall surface. Correlation analysis was done with Pearson statistics. In multivariate situation, linear regression was performed according to univariate results and clinical relevance.

Results: Fifty-three CD patients were included (57% female), with a median age of 31 [21–44] years and a median CD duration of 3.5 [1.0-9.0] years at the inclusion time. Thirteen patients (24.5%) had pure ileal disease (L1 according to Montreal classification), 12 (22.7%) had colonic disease (L2), and 28 (52.8%) had ileocolonic CD (L3). The median CDAI and CRP were 198.5 [101-258] and 11.40 [4.20-33.70] mg/L, respectively. Median CDEIS was 3.6 [2.66 – 6.4]. Endoscopic ulcerations were reported in 40 patients (75.5%).

Fecal calprotectin level was correlated with CDEIS (0.66, p < 0.001). In univariate analysis, fecal calprotectin was correlated with the affected surface (0.65, p < 0.001) and the ulcerated surface (0.47, p < 0.001). Fecal calprotectin was significantly associated with ulcerations depth, with median fecal calprotectin values of 867.5µg/g, 1251.0µg/g and 1800.0µg/g, for non-ulcerated lesions, superficial ulcerations and deep ulcerations, respectively. Lesions locations (ulcerated or not) did not influence fecal calprotectin level.

In multivariate analysis, fecal calprotectin level was associated with affected surface (p=0.04) and the presence of CD lesions. Moreover, fecal calprotectin increased with the ulcerations depth (p=0.03). However, ulcerated surface and CD location did not impact fecal calprotectin.

Using a ROC curve, we showed that fecal calprotectin ≥ 400µg/g was the best compromise between sensitivity (0.76) and specificity (0.77) (AUC (95% CI) =0.795, (0.624-0.966)) to detect CD superficial or deep ulcerations. A cut off value of 200 µg/g detected superficial or deep ulcerations with sensitivity, specificity, positive predictive value and negative predictive value of 0.86, 0.70, 0.86 and 0.70, respectively.

Conclusion: Fecal calprotectin is a very reliable biomarker to detect endoscopic ulcerations in CD. We suggest to repeat measurement for intermediary results (200-400µg/g) in daily practice. Fecal calprotectin level is not related to CD location but is mostly influenced by the affected surface and the presence of CD lesions (even non-ulcerated), with high impact of deep ulcerations.

Disclosure of Interest: None declared

P0327 POSTOPERATIVE RECURRENCE IN CROHN’S DISEASE: NATURAL HISTORY, RISK FACTORS AND MANAGEMENT STRATEGIES IN A RETROSPECTIVE COHORT (1986-2015)

A. Buisson¹², A.-L. Boucher¹, M. Goutte¹², F. Goutorbe¹, S. Decousus³, A. Dubois⁴, P. Dechelotte³, B. Pereira⁵, G. Bommelaer¹

¹Gastroenterology department, University Hospital Estaing, ²Microbes, Intestine, Inflammation and Susceptibility of the Host, UMR 1071 Inserm/Université d'Auvergne; USC-INRA 2018, ³Pathology Department, ⁴Digestive Surgery Department, University Hospital Estaing, ⁵DRCI, Biostatistics Unit, GM Clermont-Ferrand University and Medical Center, Clermont-Ferrand, France

Contact E-mail Address: a_buisson@hotmail.fr

Introduction: As surgical resection is not curative, postoperative recurrence (POR) remains a crucial issue in Crohn's disease (CD). Several factors have been considered as POR predictors, but their true impact remains debated. Recently, the POCER trial[1] suggested that an early endoscopic-based management (EBM) decreased the risk of endoscopic POR at 18 months. However the long-term impact of EBM remains unknown.

Aims & Methods: We aimed to describe the natural history, the risk factors, and the optimal prevention strategy of POR in CD.

From the pathology department database, we retrieved the data of all the patients who underwent intestinal resection for CD in our centre between 1986 and 2015. Surgical POR was defined as re-operation for CD. Clinical POR was defined as symptoms recurrence leading to hospitalization or therapeutic modifications. Endoscopic POR was defined as a Rutgeerts’ score ≥ i2. Patients were classified as Endoscopic-based management (EBM) if they underwent a systematic colonoscopy with no clinical POR. Considering the censored data, multivariate analyses were performed according to univariate results (log rank tests) and clinical relevance.

Results: Among the 161 CD patients, 59% were females, 33% active smokers, 33% had previous intestinal resection and 47% had previous perineal lesions (37% with abscess/fistula). Mean age at surgery was 37 ± 13.5 years.

The rates of POR were:

	1 year	5years	10 years	15 years	20 years
Surgical POR (%)	1.3	19.0	38.9	57.7	64.7
Clinical POR (%)	21.5	61.4	75.9	88.7	92.5
Endoscopic POR (%)	31.7	67.6	79.7	91.1	95.5

In multivariate analysis, fistulizing CD (B3 according to Montreal classification) (Hazard ratio: HR 1.78 [1.04-3.04], p=0.003) and previous intestinal resection (HR 1.7 [1.00-2.72]; p=0.05) were predictive of surgical POR. Previous intestinal resection (HR 1.65 [1.10-2.48]; p=0.02) and previous perineal abscess or fistula (HR 1.48 [1.01-2.19] ; p=0.048) were predictive of clinical POR. Fistulizing CD (HR 1.78 [1.04-3 .04] ; p= 0.03) and previous intestinal resection (HR 1.7 [1.00-2.92]; p=0.05) were predictive of endoscopic POR. In our cohort, no other factor, including smoking and resection length, were POR predictors. Neither anti-TNF agents nor thiopurines therapies decreased the risk of POR.

The median interval between surgery and endoscopy was 9.5 [5.6-54.2] months) in the EBM group (n=49/161). An EBM decreased the risks of clinical (HR 0.4 [0.25-0.66]; p< 0.001) and surgical POR (HR 0.31 [0.13-0.73]; p=0.007).

Conclusion: POR remains common in CD. The identification of risk factors may enable targeted strategies to reduce this recurrence rate. EBM should be recommended in all CD patients within the first year after surgery as it highly decreased the long-term risk of POR.

Disclosure of Interest: None declared

P0328 DEVELOPMENT OF A SMALL BOWEL CAPSULE ENDOSCOPIC INDEX OF SEVERITY IN PATIENTS WITH CROHN’S DISEASE

A. Bourreille¹², A. Attar³, V. Maunoury⁴, M. Simon⁵, L. Picon⁶, M. Fumery⁷, S. Viennot⁸, C. Reenaers⁹, I. Nion-Larmurier¹⁰, J. Filippi¹¹, B. Bonaz¹², O. Dewit¹³, X. Dray¹⁴, J. Moreau¹⁵, R. Altwegg¹⁶, X. Roblin¹⁷, C. Stefanescu³, J.-Y. Mary¹⁸, on behalf of the GETAID

¹Institut des Maladies de l'Appareil digestif, ²Inserm CIC-04, University Hospital, Nantes, ³Pole des Maladies de l'Appareil Digestif, University Hospital Beaujon, Clichy, ⁴Gastroenterology, university Hospital, Lille, ⁵Gastroenterology, University Hospital saint Louis, Paris, ⁶Gastroenterology, University Hospital, Tours, ⁷Gastroenterology, University Hospital, Amiens, ⁸Gastroenterology, University Hospital, Caen, France, ⁹Gastroenterology, University Hospital Sart Tilman, Liege, Belgium, ¹⁰Gastroenterology, University Hospital, Paris, ¹¹Gastroenterology, University Hospital, Nice, ¹²Gastroenterology, University Hospital, Grenoble, France, ¹³Gastroenterology, university Hospital, Louvain, Belgium, ¹⁴Gastroenterology, university Hospital Lariboisiere, Paris, ¹⁵Gastroenterology, university Hospital, Toulouse, ¹⁶Gastroenterology, university Hospital, Montpellier, ¹⁷Gastroenterology, University Hospital, Saint Etienne, ¹⁸Biostatistic, Inserm, Paris, France

Contact E-mail Address: arnaud.bourreille@chu-nantes.fr

Introduction: The capsule endoscopy is the most powerful exam to detect small bowel (SB) mucosal lesions in patients with Crohn’s disease (CD) but the disease severity remains difficult to evaluate. The aim of this study was to develop prospectively a new index of severity devoted to the small bowel using the Pilcam® SB capsule

Aims & Methods: Patients with CD were prospectively enrolled between June 2007 and May 2013. Inclusions were stratified according to the SB disease location in a ratio 1/1/2/2 (none, ulcer at endoscopy only, non severe and severe at radiology whatever endoscopy) crossed with clinical activity in a ratio 3/1 (active or not) to ensure a wide range of severity of the SB lesions. The SB was divided into 3 tertiles from the duodenum to the caecum or to the end of the record. When possible, the terminal ileum (TI) was defined as the last 15 cm above the caecal valve. All lesions i.e. erythema, oedema, villous denudation, nodularity, lymphangiectasia, pseudo-polyp, aphtous lesions, ulcerations in relation to size, depth and shape were described, fistulas and stenosis were quantified according to predefined frequency. The extension in length of oedema, in length and circumference of ulcerations were quantified according to predefined proportions. The surface and length of lesions and ulcerations were quantified on linear analog scales. The severity physician global assessment (PGA) for each segment and for the whole SB, was assessed on a linear analog scale. Multiple linear mixed model was used to construct the new severity index in two ways as a linear combination of lesions, lengths and surfaces highly correlated either to the whole SB or to the segmental severity PGAs. Random factors were used to take into account the dependency of estimates performed in different segments of the same patient or by the same investigator on different patients.

Results: 118 patients (33 yrs [25-44]) were enrolled, 23, 21, 41 and 33 according to disease lesion strata, 76 and 42 according to clinical activity strata. Seven films were unusable for the construction of the index because of missing data or a prolonged stay in the stomach. The colon was identified in 80 patients (71%). The extension of oedema, the presence of >8 ulcerations (> 10mm or superficial), the presence of deep or circular ulcerations, the extension of ulcerations in length or circumference, the lesion surface and ulceration length, and the presence of stenosis were highly related to severity, whereas the presence of villous denudation, lymphangiectasia, pseudo-polyp or aphtous lesions was clearly not

Conclusion: The preliminary results of this prospective study highlights the importance of oedema, deep and circular ulcerations and the extension of the disease in evaluating the severity of SB lesions to build this new index

Disclosure of Interest: A. Bourreille Lecture fee(s): Covidien, A. Attar: None declared, V. Maunoury: None declared, M. Simon: None declared, L. Picon: None declared, M. Fumery: None declared, S. Viennot: None declared, C. Reenaers: None declared, I. Nion-Larmurier: None declared, J. Filippi: None declared, B. Bonaz: None declared, O. Dewit: None declared, X. Dray Lecture fee(s): Covidien, J. Moreau: None declared, R. Altwegg: None declared, X. Roblin: None declared, C. Stefanescu: None declared, J.-Y. Mary: None declared

P0329 RECEIVING CORTICOSTEROIDS THERAPY IS ASSOCIATED WITH A POOR OUTCOME IN PATIENTS WITH ELDERLY-ONSET ULCERATIVE COLITIS: A POPULATION-BASED STUDY

B. Pariente¹, M. fumery², H. Sarter¹, L. Armengol-Debeir³, L. Dauchet¹, E. Laberenne⁴, H. Coevoet⁵, L. Peyrin-Biroulet⁶, C. Gower-Rousseau¹, G. Savoye³

¹CHRU Lille, University Lille 2, Lille, ²CHRU Amiens, Amiens, ³CHU Rouen, Rouen, ⁴CHR, Seclin, ⁵Arras, Arras, ⁶CHU Nancy, Nancy, France

Contact E-mail Address: benjamin.pariente@chru-lille.fr

Introduction

Background: In elderly-onset ulcerative colitis (UC) patients, clinical course has been reported to be mild, with a rare disease extension and a majority of patients never exposed to any immunosuppressant (IS) or anti-TNF-therapy, nor operated. Nevertheless, some patients have poor clinical outcome with early resort to surgery. Along this, the impact of receiving corticosteroids (CS) therapy on the evolution of elderly-onset UC has not been evaluated.

Aims & Methods

Methods: In a French population-based cohort we identified from 1988 to 2006 473 UC patients >60 years of age at diagnosis with a median follow-up of 6.3 years [Q1=2.3-Q3=10.3]. Clinical outcome of patients undergoing CS (CS group) was compared with patients who never received CS (control group) after adjustment on receiving or not IS and/or biothérapies (as clinical surrogate marker), and on colonic location and disease duration.

Results: Among the 473 UC patients, 157 (33%) received at least one time CS therapy (prednisone or prednisolone in 97% of cases). The cumulative probabilities of receiving CS was 21% (95% CI: 17-25) at 1 year, 39% (34-45) at 5 years, and 45% (38-52) at 10 years. Gender, median age and presence of extraintestinal manifestations at diagnosis were not different in CS and control groups. In CS group, proctitis (21%) was less frequent and pancolitis (36%) more frequent compared to control group (32% and 21% respectively, p < 10⁻²). At maximal follow-up, 7% and 49% of patients in CS group had proctitis and pancolitis respectively, compared to 22% and 26% in control group respectively (p < 10⁻⁴). Colectomy rate was higher in CS group (13%) than in control group (4%, p=10⁻³). Total number of flares and hospitalizations per year but also time spent in hospital were significantly higher in CS group compared to control group (p < 10⁻⁴). The median duration of CS exposure was 4.6 months (2.4–9.0). Thirty-two (20%) patients were CS-dependent, 14 (9%) CS-resistant, and 15 (10%) became intolerant to CS (in which almost 30% of patients developed insulin-dependent diabetes). The cumulative probabilities of developing intolerance to CS was 1.3% (0.0 ; 4.0), 6.7% (2.6 ; 16.4) et 17.3% (8.1 ; 34.6) at 1, 5, and 10 years respectively. Four patient stopped CS because of intolerance.

Conclusion: In elderly-onset UC, receiving CS therapy is associated with a more pejorative evolution of the disease, with higher rate of surgery, flares and hospitalization. Moreover a significant proportion of patients become intolerant to CS with more than one third who developed diabetes. Unlike the majority of cases in elderly-onset UC, IS or anti-TNF treatments should be early considered in patients receiving CS.

Disclosure of Interest: None declared

P0330 SMALL BOWEL CAPSULE ENDOSCOPY IN ULCERATIVE COLITIS – THE CAPCOLITIS STUDY: A PROSPECTIVE OBSERVATIONAL STUDY IN GERMANY

D. Luehr¹, B. Bokemeyer²³, U. Helwig⁴, C. Maaser⁵, P. Jessen⁶, S. Schreiber²

¹Clinic for Gastroenterology, Johannes Wesling Klinikum, Minden, ²Clinic of General Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, ³Gastroenterology Practice Minden, Minden, ⁴Gastroenterology Practice, Oldenburg, ⁵Medizinische Klinik, Klinikum Lüneburg, Lüneburg, ⁶Gastroenterology Practice, Altenholz, Germany

Contact E-mail Address: bernd.bokemeyer@t.online.de

Introduction: From the genetic point of view ulcerative colitis (UC) and Crohn's Disease (CD) are not strictly separated in genome-wide association studies (GWAS). This was the reason to investigate UC-patients with a Small Bowel Capsule Endoscopy (SBCE). The nationwide BioColitis Registry (Biological Registry with Ulcerative Colitis Patients in Germany) of the German Competence-Network IBD is a five-year prospective registry of about 1.000 patients with ulcerative colitis (UC) in Germany. The CapColitis Study is a sub-study of the BioColitis Registry reporting the results of a SBCE in these UC-patients.

Aims & Methods: The primary study objective was to describe the type and frequency of small bowel lesions detected by SBCE in UC-patients and secondary to evaluate the prognostic impact of SBCE in new TNF-therapies. Within the framework of this non-interventional prospective online documentation, data in respect to the results of the SBCE and the course of disease, psychosocial burden, health economics and the genetic profile were analyzed. Until April 2015 about 500 UC-patients have been included in the BioColitis Study, the recruitment is ongoing. End of 2014 the recruitment of the CapColitis study was stopped having analyzed the data of 127 UC-patients with a SBCE in early disease UC-patients (disease duration < 2 years) and in UC-patients (n=57) starting with an anti TNF-alpha antibody therapy (TNF) included by 11 gastroenterology practices and hospitals with IBD-experience. All patients will have a prospective 5 year follow-up period. The data of the baseline and the 6-months visit will be analyzed.

Results: 127 UC-patients have been examined with SBCE and 125 SBCE (incomplete small bowel examination (n=2); no capsule retention) could be analyzed (average age: 40 years; female: 47%; disease duration: 4.5 years; pancolitis: 42%, NSAIDs 0%). Small bowel lesions/inflammation have been found in 16/125 UC patients (13%). These 16 patients with small bowel lesions/inflammation could be divided in different categories: only single-non-relevant small bowel lesions (n=7) (PE-induced-lesions (n=3); single-non-relevant lesions (n=4)) and pathologic findings in 9 UC-patients (backwash ileitis in active pancolitis (n=4); switch to Crohn's Disease (n=5; 4%) after discussing all findings with the study centers). The findings in the 57 UC-patients starting a TNF-therapy have not been significantly different compared with the early disease group.

Conclusion: In this real life setting SBCE showed small bowel lesions/inflammation in 13% in these NSAIDs free UC-patients with relevant findings in 9/125 (7%), perhaps indicating an overlapping phenotyp between UC and CD as shown earlier in the partial genetic association of UC and CD in the entirety of inflammatory bowel diseases (IBD). In 5/125 UC-patients (4%) the diagnosis have been switched following the SBCE-findings to CD. In accordance with the UC-guidelines a small bowel diagnostic is required at the point of UC-diagnosis and in this case SBCE seems to be a sensitive procedure, possibly better suited than small-bowel MRT.

Disclosure of Interest: D. Luehr: None declared, B. Bokemeyer Financial support for research: Abbvie, Ferring, UCB, Lecture fee(s): Abbvie, Ferring, MSD, Merckle, Falk, HLR, UCB; Takeda, Consultancy: Abbvie, MSD, Shire, Ferring, UCB, Hospira, U. Helwig: None declared, C. Maaser: None declared, P. Jessen: None declared, S. Schreiber: None declared

P0331 NETWORKING AND IMPLEMENTATION OF EVIDENCE-BASED PATHWAYS FOR PATIENTS WITH INFLAMMATORY BOWEL DISEASES (IBD)

B. Bokemeyer¹², J. Langbrandtner³, P. Jessen⁴, H. Raspe³, A. Hüppe³

¹Clinic of General Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, ²Gastroenterology Practice Minden, Minden, ³Institute of Social Medicine and Epidemiology, University of Luebeck, Luebeck, ⁴Gastroenterology Practice, Altenholz, Germany

Introduction: IBD-patients experience various somatic and psychosocial impairments. They need a comprehensive, interdisciplinary and problem-oriented health care. To improve their quality of health care IBD-pathways recommend a systematic assessment of health-related problems and focus on a multidisciplinary, patient-centered care. In a prospective controlled cohort study German gastroenterologists tried to optimize their quality of care by network activities. The impact on patient reported outcomes was evaluated.

Aims & Methods: In a region of North Germany 15 gastroenterologists recruited outpatients with IBD (IG: intervention group), outside this region 18 gastroenterologists included nationwide IBD-patients in a control group (CG). At baseline (t0), 6 (t1) and 12 months (t2) patients completed a questionnaire assessing 22 somatic and psychosocial problems. Medical data on the course of disease were gathered by the gastroenterologists. IG-patients received written feedback of their problem-profile together with individualized recommendations for appropriate treatment. Further IG-interventions were the implementation of interdisciplinary IBD-case conferences and the offer of a patient training in small groups. Main outcomes were health related quality of life (HRQoL: EQ-VAS, score: 0-100) and social participation restrictions (IMET, score: 0-10); self-management skills (heiQ) and work productivity (WPAI) were among the secondary outcomes.

Results: 282 of 349 IBD-patients (80.8%; IG: 142 of 189; CG: 140 of 160) participated in both follow-up visits. Baseline characteristics were broadly similar (age: 43 years; 61% female; 50% with Crohn's Disease; 66% in remission; 68% in full- or part time employment). Only minor differences between IG and CG for age, school education and medication could be found. Covariance analyses were used to adjust for baseline differences. No significant differences between IG and CG were seen at follow-up with respect to the primary outcomes, the entire group showed small improvements from t0 to t2 (EQ-VAS: 72.5 to 76.2, p=0.002; IMET: 2.1 to 1.9; p=0.025). After 12-months only the IG reported increased self-management skills, the CG remained nearly unchanged (treatment x time interaction: p=0.002). Work productivity of both groups was unimproved. In contrast, the feedback of the physicians in the IG were more favourable at the 6-months follow-up. 67% of the physicians participated in IBD-case conferences, the benefit of networking has been ranked with 7 on a scale from 0 (no benefit) - 10 (best benefit).

Conclusion: Our complex intervention could not be proved as effective and beneficial in the primary outcomes. Both groups showed slight positive effects over the 12 months. In a secondary outcome (self-management skills) we found an advantage for the intervention-group. The missing differences between IG and CG could be partially explained by (i) a positive side effect in the CG caused by the systematic medical documentation during the study and (ii) by the fact, that not all network activities in the IG could have been realised in the aimed frequency. Further (sub group) analysis will promote the discussion.

Disclosure of Interest: B. Bokemeyer Financial support for research: Abbvie, Ferring, UCB, Lecture fee(s): Abbvie, Ferring, MSD, Merckle, Falk, HLR, UCB, Takeda, Consultancy: Abbvie, MSD, Shire, Ferring, UCB, Hospira, J. Langbrandtner: None declared, P. Jessen: None declared, H. Raspe: None declared, A. Hüppe: None declared

P0332 NON-INVASIVE TESTING IS DIAGNOSTIC AND PROGNOSTIC IN INTESTINAL GRAFT VERSUS HOST DISEASE

B. H. Hayee¹, P. Pavlidis¹, L. Floro², K. Raj², D. McLornan², H. de Lavallade², T. Pagliuca², V. Potter², G. Mufti²

¹Gastroenterology, ²Haematology, King's College Hospital, London, United Kingdom

Contact E-mail Address: b.hayee@nhs.net

Introduction: Intestinal graft versus host disease (iGVHD) is a debilitating and sometimes fatal consequence of bone marrow transplantation[1]. Malnutrition and profuse diarrhoea are common. The diagnosis is often based on clinical criteria alone and intestinal biopsies are frequently negative[1,2]. Even after successful treatment, iGVHD can relapse and reliable disease monitoring is unavailable.

Aims & Methods: We conducted this prospective study to evaluate the diagnostic accuracy of the xylose/rhamnose/lactulose small bowel permeability test (SBPT) and faecal calprotectin (FC) in the work-up of patients with suspected iGVHD. Prospective data was collected on all patients referred for endoscopic investigation of suspected iGVHD at KCH, from Jan-Dec 2014. All patients underwent OGD and colonoscopy to at least the caecum, with serial intestinal biopsies taken. Samples were collected for SBPT and FC. Infection and other pathologies were excluded with extensive testing. SBPT and FC results were compared to biopsy results and the site of positive biopsies was noted.

Results: 15 patients had positive intestinal biopsies (PB) with 9 negative (NB). SBPT was unavailable in 2, and FC in 1 patient in each group. SBPT was abnormal in 1/7 NB and in 11/13 PB. The sensitivity (Sn) and specificity (Sp) for SBPT in the diagnosis of iGVHD was 84.6% and 85.7% respectively; PPV 91.7%. FC was high in 2/8 NB and 9/14 PB, returning Sn 64.2% and Sp 75%. Addition of the two tests reduced sensitivity and specificity further. Mortality was high in the PB group (6/14, 43% - exclusively from gram-negative sepsis +/− multi-organ failure). FC was elevated >300mcg/g in 5/6 deaths and 2/8 survivors. Intestinal biopsies were positive in all but one case from the right hemicolon, 3/6 ileum and only 2/15 from duodenum. At present, no significant patterns have emerged with regard to conditioning regimen or other aspects of the transplant protocol.

Conclusion: SBPT appears to be a highly sensitive and specific marker of iGVHD. A high FC does not appear to be related to iGVHD itself, but may predict severe disease and mortality. Biopsies were most often positive at full colonoscopy in our cohort. These non-invasive tests are simple and cheap and may serve to assist clinicians in the investigation and management of this debilitating condition.

Disclosure of Interest: None declared

P0333 ULTRASOUND SHEAR WAVE ELASTOGRAPHY IDENTIFIES MUSCLE WALL HYPERTROPHY AND IS A NOVEL SURROGATE FOR INFLAMMATION IN CROHN'S DISEASE

C. Lu¹, X. Gui², W. Chen², S. Ghosh¹, K. Novak¹, S. Wilson³

¹Gastroenterology, ²Pathology and Laboratory Medicine, ³Diagnostic Imaging, University of Calgary, Calgary, Canada

Contact E-mail Address: clu@ualberta.ca

Introduction: Crohn’s Disease (CD) is an inflammatory bowel disease mainly affecting the terminal ileum. Inflammation, fibrosis, and muscular hypertrophy lead to thickened and narrowed bowel detected on ultrasound (US). US shear wave elastography (SWE) assesses elastic properties of tissue through an acoustic US force providing a quantitative measurement of tissue stiffness. SWE has been described to differentiate inflammation from fibrosis in ex vivo CD bowel specimens¹. As confirmed on histology, neo-angiogenesis is an important component of CD bowel wall inflammation. Quantification of bowel wall vascular perfusion can be uniquely detected by contrast enhanced ultrasound (CEUS).

Aims & Methods: We aim to prospectively correlate SWE of ileal CD in-vivo to CEUS peak enhancement as a measurement of inflammation, and to pathology grades of inflammation, fibrosis, and muscular hypertrophy of resected small bowel. We predict patients with a higher SWE score will have greater bowel stiffness attributable to fibrosis and muscular hypertrophy, and concurrent chronic inflammation as measured by lower CEUS peak enhancement. All consecutive CD patients (March to October 2014) attending outpatient US appointments received greyscale US. In patients with ileal CD and bowel wall thickness (BWT) > 3mm, SWE was measured at a point of maximal BWT and CEUS peak enhancement using microbubble (Definity®) contrast was performed (n=95). An average of ten SWE readings were collected using Virtual Touch Quantification; Acuson S3000, Siemens Medical Solutions USA, Inc or with Philips Epiq 5, (Bothell, WA). Receiver operating characteristic (ROC) curve analysis was performed. Differences in low and high inflammation, fibrosis, and muscular hypertrophy of bowel specimens were compared using the student t-test. Of these 95 patients, fifteen had ileal resections within an average of 47 days (SD 90.4 days) from the time of CEUS. A gastrointestinal pathologist scored these specimens for inflammation, fibrosis, and muscular hypertrophy for comparison to SWE measurements of the corresponding regions.

Results: Of fifteen ileal specimens, chronic inflammatory histological change (p < 0.001) with lower corresponding CEUS peak enhancement (p=0.04) exceeded acute inflammatory changes. Mean in-vivo SWE measurements for all patients who had and did not have surgery were 2.82 ± 0.68 m/s and 2.17± 0.79m/s (p < 0.01), respectively. Of the operated patients with a SWE > 3m/s, there was an inverse relationship with inflammation matching to lower CEUS peak enhancement (p=0.04), and more smooth muscle hypertrophy (p=0.03). There was no significant difference in SWE and fibrosis scores (p > 0.05).

Conclusion: SWE measurements of in vivo small bowel CD increases when there is smooth muscle hypertrophy. Overall, CD patients with lower CEUS peak enhancement parameters have more chronic bowel inflammation as confirmed on histology. A novel observation; higher SWE is related to bowel smooth muscle hypertrophy, and is inversely related to both chronic inflammation and CEUS peak enhancement. In vivo SWE and CEUS differentiates between acute and chronic bowel wall inflammation and thickening, improving selection between medical therapy and surgery.

Disclosure of Interest: None declared

P0334 PERFORMANCE TESTING OF A SMARTPHONE-BASED PATIENT MONITORING SYSTEM MEASURING CALPROTECTIN AS IBD THERAPY FOLLOW-UP MARKER BY LAY USERS VERSUS LABORATORY PROFESSIONALS

J. Weber¹, P. Spies², M.-E. Ueberschlag¹, C. Reinhard¹, S. Kräuchi¹, T. Jermann¹

¹BÜHLMANN Laboratories AG, Schoenenbuch, ²University of Applied Life Sciences, Muttenz, Switzerland

Contact E-mail Address: jw@buhlmannlabs.ch

Introduction: Inflammatory Bowel Disease (IBD) is a chronic inflammation of the gut comprising active inflammation, remission and flares. The disease course can be followed by biomarkers such as calprotectin which is measured in patients’ stool samples. Most studies have shown that a threshold around 250 µg/g correlates well with mucosal healing. Hence, one of the therapy goals is to achieve calprotectin values below 250 µg/g and to keep them below this level. Therefore, we have developed a system, called IBDoc^®, which allows the patient to perform calprotectin tests at home in order to regularly test that this low level is under control. The IBDoc^® consists of a stool extraction device (CALEX^® Valve) and an immunochromatographic rapid test, which is measured by a smartphone App (CalApp^®) controlling the phone’s camera. Results are automatically sent to and administered on a webserver (IBDoc^® Portal) for the consulting physician or IBD nurse.

Aims & Methods: The objective of this study was to validate the IBDoc^® home testing system by lay users vs. professional laboratory personnel and to compare its quantitative performance with routine laboratory-based methods.

Stool samples containing various levels of calprotectin (18-2582 µg/g), kindly provided by a local routine clinical laboratory, were extracted with the CALEX^® Valve device by 31 lay users and two laboratory professionals. The stool extracts were then either loaded by the lay users onto immunochromatograhic test cassettes (TCs) or analyzed with a commercial ELISA test by the professional users. The lay users read the TCs via the CalApp^® installed on 11 different models of iPhones and Android phones, whereas the professional users measured the TCs with the Quantum Blue^® (QB) lateral flow reader. Agreement between lay users and professional users as well as quantitative performance of IBDoc^® versus routine laboratory methods were assessed by Analyze-it for Microsoft^® Excel.

Results: The IBDoc^® test system produces a quantitative test result between 30 and 1000 µg of calprotectin/g of stool which covers the clinically relevant range of this biomarker. The total agreement (TA; based on a traffic-light system) of performing IBDoc^® between lay users and laboratory professionals was 96.8% with 0% false positive and 0% false negative rates. The TA between measuring the TCs with 11 different smartphone models and the QB reader was 90.3%, whereas the TA of CALEX^® Valve extractions performed by lay vs. professional users was 80.6%. The IBDoc^® home test performed by 31 lay users correlated well with a state-of-the-art laboratory-based fCAL^® ELISA method showing a slope of 1.03, a bias of 40 µg/g and R² of 0.941. The TA of these 31 single test results was 87.1%, and no false positive (red instead of green traffic-light) or false negative result (green instead of red traffic-light) was reported.

Conclusion: IBDoc^® is the first complete and validated test system which allows the IBD patient to monitor and follow his inflammatory status by measuring the IBD biomarker, fecal calprotectin, using his/her own smartphone. The performance of the IBDoc^® home testing system is comparable to professional, laboratory-based methods. IBDoc^® is the first CE-marked self testing home device of its kind.

Disclosure of Interest: J. Weber Conflict with: Employee of BÜHLMANN, P. Spies Financial support for research: BÜHLMANN Laboratories, M.-E. Ueberschlag Conflict with: Employee of BÜHLMANN, C. Reinhard Conflict with: Employee of BÜHLMANN, S. Kräuchi Conflict with: Employee of BÜHLMANN, T. Jermann Conflict with: Employee of BÜHLMANN

P0335 FREQUENCY OF UNDIAGNOSED IBD AMONG PATIENTS UNDERGOING SURGERY FOR PERIANAL ABSCESS OR FISTULA

C. Zenz¹, P. Kornprat², A. Szyszkowitz³, A. Berghold⁴, W. Petritsch¹, A. Berger³, H. H. Wenzl¹

¹Gastroenterology and Hepatology, ²Surgery, Medical University of Graz, ³Surgery, Krankenhaus der Barmherzigen Brüder Graz, ⁴Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria

Contact E-mail Address: heimo.wenzl@klinikum-graz.at

Introduction: Many patients with penetrating Crohn’s disease (CD) undergo surgery for perianal disease of presumed cryptoglandular etiology before diagnosis of IBD is established.

Aims & Methods: This study aimed for the first time (1) to determine the frequency of postoperative IBD diagnosis (Dx-POP) among patients undergoing surgery for perianal abscess or fistula, and (2) to identify predictive factors for Dx-POP.

Patients who underwent surgery for perianal abscess or fistula at two major surgical departments in the city of Graz, Styria, between 1997 and 2007 were searched electronically. Dx-POP patients were identified by a registry containing all patients who received a first diagnosis of IBD between 1997 and 2007 and were residents of Styria. Dx-POP patients were compared with sex- and age-matched non-IBD controls (CO) (ratio 1:3).

Results: Among 975 patients included (73% male; age 46 ± 14 y) 58 had a pre-existing diagnosis of IBD (52 CD, 6 UC). Twenty-two patients received a first diagnosis of IBD (18 CD, 4 UC) 0.1-70 months (median; CD 9, UC 24) after surgery. Age at surgery of patients with and without a first diagnosis of CD during follow-up was 28 ± 9 and 47 ± 14 years, respectively (p < 0.001). According to life-table analysis, the cumulative risk of non-IBD patients to receive a diagnosis of IBD within 11 years after surgery was 2.9% (CD 2.5%, UC 0.4%). Clinical and laboratory results of Dx-POP vs. CO are compared in the Table.

	Dx-POP	CO	p
N	22	66
Median age (y)	28	28
Male (%)	63.6	63.6
Number of patients with fistula/abscess/both	4/8/10	20/36/10	0.013
Fistula simple/komplex (%)	64/36	90/10	0.039
Abscess type P/I/IR/S/H* (%)	44/17/22/6/11	85/11/4/0/0	0.004
Mean (±SD) hemoglobin (g/dL)	13.4 ± 1.5	14.8 ± 1.6	0.002
Median (IQR) platelets (103/µL)	321 (265-428)	249 (213-291)	0.001
Mean (±SD) ESR after 2h (mm)	57 ± 30	29 ± 28	0.026
Median (IQR) length of hospital stay (d)	5 (4-6)	4 (3-5)	0.007

*P, perianal; I, interspincteric; IR, ischiorectal; S, suprasphincteric; H, horseshoe

Conclusion: A small but important fraction of patients operated for perianal abscess or fistula will receive a diagnosis of IBD during follow-up. Young age, more complex perianal disease, low hemoglobin, and high platelets at surgery predict future diagnosis of IBD. Surgeons need to be aware of undiagnosed IBD when operating perianal lesions.

Disclosure of Interest: None declared

P0336 CLINICAL AND SONOGRAPHIC OUTCOME OF INTESTINAL FISSURING-TYPE ULCERS IN CROHN’S DISEASE

C. Bezzio¹, F. Furfaro¹, A. Dell'Era¹, G. Delconte², S. Carmagnola¹, S. Ardizzone¹, A. Cassinotti¹, R. de Franchis¹, G. Maconi¹

¹Gastroenterology, AO Luigi Sacco Milano, ²Endoscopy, IRCCS Istituto Nazionale Tumori, Milano, Italy

Contact E-mail Address: cristina.bezzio@unimi.it

Introduction: Crohn’s disease (CD) is frequently complicated by intestinal strictures, fistulae and abscesses. The natural course of intestinal fistulae, in particular early enteromesenteric lesions like fissuring-type ulcers originating from penetrating ulcers, is not well known.

To date, the possibility to accurately detect these lesions (IUS) by means of intestinal ultrasound, as hypoechoic irregularities of the outer margins of the intestinal wall, allows us to obtain information regarding their natural history in relation to treatment and clinical features of the disease.

Aims & Methods: The aim of this study was to evaluate the clinical features and outcome, of a cohort of patients with Crohn’s disease complicated by intestinal fissuring-type ulcers.

We retrospectively identified 40 CD patients (male 23; mean age, 48 years) regularly followed in our Unit, in whom an intestinal ultrasound has detected intestinal fissuring ulcers, in absence of any other intestinal complications. All these patients had a regular clinical and sonographic follow up. The features of these patients and their clinical outcome, namely the need of surgery, biological or immunosuppressive therapy, as well as the sonographic behaviour of the lesions over time, including their disappearance or worsening into a evident intestinal fistula or abscess, have been evaluated.

Results: Eleven patients were active smokers, 22 had an ileal, 16 an ileocolic and 2 a colic CD. Four patients had a concomitant perianal disease. In 14 patients (35%) intestinal fissuring ulcers worsened, becoming an intrabdominal abscess (2 pt) or an evident internal fistula (12 pts) in a mean follow up of 2 years. Four of these patients had been treated immunosuppressive therapy, 2 also with biological therapy. Ten patients (25%) underwent surgery within 2 years, 6 of them despite the treatment with immunosuppressive therapy (2 pt) or biologics (4 pt). Fourteen patients (35%) showed the complete disappearance of the fissuring ulcers, 10 of them (71.4%) had been treated with azathioprine plus biologics (8 patients) or azathioprine alone (2 patient). Two patients (5%) under treatment with mesalamine showed the persistence of fissuring ulcer after 2 years.

Conclusion: This preliminary report showed that intestinal fissuring-type ulcers complicating CD seem to have progression into evident internal fistulae and a poor clinical outcome and in most patients. These lesions seem to disappear in less than one-third of patients and in most of these cases this is correlated with immunosuppressive and biological therapy.

Disclosure of Interest: None declared

P0337 INFLAMMATORY BOWEL DISEASE ACTIVITY AND VITAMIN D DEFICIENCY: AN ASSOCIATION?

C. Teixeira¹, D. Trabulo¹, S. Ribeiro¹, C. Martins¹, I. Cremers¹, A. L. Alves¹, A. P. Oliveira¹

¹Gastrenterology, Centro Hospitalar de Setubal, Setubal, Portugal

Contact E-mail Address: ac.corda.teixeira@gmail.com

Introduction: Vitamin D deficiency is commonly diagnosed among patients with inflammatory bowel disease (IBD). Recent studies suggest that vitamin D may have a role in clinical disease activity in ulcerative colitis (UC) and Crohn's disease (CD).

Aims & Methods: This study aims to assess an association between vitamin D levels and clinical disease activity in patients with IBD.

Prospective study with 1 year recruitment in a Southern European Center. Demographic and clinical data of patients with IBD were collected. C-reactive protein (CRP) and vitamin D levels within 30 days of their clinic visit were measured. Seasonality of the data was also considered. Patients under vitamin D replacement were excluded. Clinical activity was defined using Truelove-Witts score in UC patients and Harvey-Bradshaw score in CD patients. Vitamin D levels were defined as: normal > 30 ng/ml; insufficient 20–29 ng/ml; deficient < 20 ng/ml. Statistical analysis was performed using SPSS 21, considering statistical significance p <0.05.

Results: One hundred and twenty patients; 57 females; mean age 45.8 years. 60 patients with UC and 60 patients with CD. Mean years of disease 9.69 (0-42). Seventy-seven patients presented deficient vitamin D levels and 40 patients had active disease. There was a statistically significant association between vitamin D deficiency and clinical disease activity in CD (P=0.005) and in UC (p=0.038). There was also a significant association between clinical disease activity and increased CRP levels in both diseases (P=0), but there was no association between increased CRP and vitamin D deficiency in any type of IBD. Despite a higher percentage of vitamin D deficiency in active disease, we found that a significant percentage of patients of patients with inactive disease had insufficient or even deficient vitamin D levels. There was not season variability.

Conclusion: In our series, vitamin D deficiency is related to clinical activity of IBD, especially in CD. Vitamin D supplementation may have a potential role as a treatment for patients with active IBD.

Disclosure of Interest: None declared

P0338 ARE CLINICAL INDICES OF INFLAMMATORY BOWEL DISEASE ACTIVITY SUPERIOR TO PATIENT OPINION AT PREDICTING ACTIVITY AS DEFINED BY FAECAL CALPROTECTIN?

D. J. Gracie¹², C. Williams², R. Sood¹², S. Mumtaz², H. Bholah², P. J. Hamlin¹², A. C. Ford¹²

¹Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, ²Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom

Contact E-mail Address: djgracie1982@doctors.org.uk

Introduction: The Harvey-Bradshaw Index (HBI) and Simple Clinical Colitis Activity Index (SCCAI) are clinical scoring systems used to estimate Crohn's disease (CD), and ulcerative colitis (UC) activity respectively. However, their performance compared with patient opinion at predicting disease activity defined by faecal biomarkers of IBD activity is unclear. We conducted a cross-sectional survey of IBD activity to assess these issues.

Aims & Methods: Demographic data and patient opinion regarding whether they were, or were not having a flare of disease was assessed by standardised questionnaire. IBD activity was assessed by HBI for CD and SCCAI for UC, with active disease defined by a score of ≥5 for each. Stool was collected for faecal calprotectin (FC) analysis by enzyme linked immunosorbent assay (ELISA) (Biohit, Finland). Patients were dichotomised into those with or without active disease using a FC of ≥200µg/g of stool to define active disease. Mean FC was compared between those with and without active disease by patient opinion and clinical indices of IBD activity by independent samples t-test. The sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of patient opinion and clinical activity indices at predicting active disease define by FC was also calculated. ROC curve for HBI and SCCAI against active disease defined by FC was used to calculate the AUC for each clinical assessment index.

Results: There was no difference in mean age, sex, education level, marital status, smoking or alcohol usage for CD or UC patients dichotomised in those with and without active disease defined by FC. In CD mean FC was lower in patients with active disease defined by HBI than those without (381 vs. 472; P = 0.368). Mean FC was higher in patients with active disease defined by patient opinion than those without but this failed to reach statistical significance (474 vs. 425; P = 0.711). In contrast, mean FC was significantly higher in UC patients with active disease defined by both patient opinion and SCCAI (919 vs. 381; P <0.001 and 949 vs. 311; P <0.001 respectively). The sensitivity, specificity, positive predictive value, negative predictive value, overall test accuracy and AUC for each test when used to predict disease activity defined by FC is illustrated in table 1.

Table 1.

performance of individuals IBD assessment tools

	Crohn's disease		ulcerative colitis
patient opinion	HBI	patient opinion	SCCAI
sensitivity	0.17	0.37	0.45	0.54
specificity	0.84	0.64	0.78	0.73
PPV	0.45	0.44	0.62	0.62
NPV	0.57	0.57	0.64	0.65
Accuracy	0.55	0.53	0.63	0.64
ROC AUC	-	0.49	-	0.66

Conclusion: The performance of clinical disease activity indices at predicting IBD activity is modest in UC and poor in CD when compared to faecal biomarkers of intestinal inflammation. Neither HBI nor SCCAI appear to outperform patient opinion. Faecal biomarker point of care testing may aid clinical decision making.

Disclosure of Interest: None declared

P0339 PREVALENCE AND IMPACT OF IRRITABLE BOWEL TYPE-SYMPTOMS IN QUIESCENT INFLAMMATORY BOWEL DISEASE

D. J. Gracie¹², C. Williams², R. Sood¹², S. Mumtaz², H. Bholah², P. J. Hamlin¹², A. C. Ford¹²

¹Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, ²Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom

Contact E-mail Address: djgracie1982@doctors.org.uk

Introduction: The prevalence of symptoms compatible with irritable bowel syndrome (IBS) in inflammatory bowel disease (IBD) has been previously described. However, the association between the presence of these symptoms and occult disease activity is less well known, as is the effect of these symptoms on psychological health. We conducted a cross-sectional survey examining these issues.

Aims & Methods: Demographic and gastrointestinal symptom data were collected from 439 adult patients via the Rome III questionnaire. IBD activity was assessed via clinical scoring systems and faecal calprotectin (FC) in a subset of patients. Mood was assessed using the hospital anxiety and depression scale, whilst somatisation and quality of life data were collected using the patient health questionnaire-12 (PHQ-12) and SF-36 questionnaire respectively. Mean FC, as well as anxiety, depression and somatisation severity and quality of life were compared between CD and UC patients meeting Rome III criteria for IBS and those who did not.

Results: More patients with CD met criteria for IBS than UC (97 (42.4%) of 229 vs. 63 (30.9%) of 204 respectively, P = 0.01). In CD, there was no difference in anxiety (P = 0.106), depression (P = 0.156) or somatisation severity (P = 0.104) when patients with IBS-type symptoms were compared to those without. Mean quality of life scores for pain (P = 0.003) and general health (P = 0.009) were significantly lower in CD patients with IBS-type symptoms. In contrast, in UC anxiety severity was higher in those with IBS-type symptoms (P = 0.001), and there was a trend towards greater depression and somatisation severity in patients with IBS-type symptoms (P = 0.035 and P = 0.011 respectively). UC patients with IBS-type symptoms had significantly lower mean quality of life scores for role limitations due to physical health (P = 0.004), energy/fatigue (P = 0.003), emotional wellbeing (P = 0.002), social functioning (P = 0.006), pain (P <0.001) and general health (P = 0.003). For CD, mean FC levels were higher in those with IBS-type symptoms than those without (543.3 vs. 444.9; P = 0.529) and the same trend was observed in UC (423.5 vs. 282.8; P = 0.368). There was no difference in the proportion of individuals with a normal FC in CD patients fulfilling criteria for IBS (12 (63.2%) of 19) than those not (31 (56.4%) of 55) (P = 0.605). The same was true in UC (7 (50%) of 14 vs. 38 (69.1%) of 55 (P = 0.181).

Conclusion: The prevalence of IBS-type symptoms is higher in CD than in UC. IBS-type symptoms are associated with more severe anxiety in UC patients and lower quality of life scores in both CD and UC. Whether such symptoms arise from occult disease activity, or true coexistence of IBS, remains unclear.

Disclosure of Interest: None declared

P0340 THE FECAL NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN (NGAL) AS NOVEL SURROGATE BIOMARKER OF INFLAMMATION IN THE DIAGNOSIS OF INFLAMMATORY BOWEL DISEASES

D. Mukhametova¹, D. *Abdulganieva¹, O. D. Zinkevich², N. A. Saphina², M. Koporulina², A. Odintsova³

¹Department of Hospital Therapy, Kazan State Medical University, ²Scientific Research Laboratory, Kazan State Medical Academy, ³Department of Gastroenterology, Republican Clinical Hospital, Kazan, Russian Federation

Contact E-mail Address: muhdilyara@gmail.com

Introduction: Today there is active search of non-invasive surrogate biomarkers of intestinal inflammation in inflammatory bowel diseases (IBD). Fecal neutrophil gelatinase-associated lipocalin (NGAL) secreted by neutrophils and epithelial cells during inflammation and possibly can be used as a biomarker of inflammation.

Aims & Methods: To evaluate the fecal concentration of NGAL in different courses of inflammatory bowel disease (IBD).

We prospectively included 96 patients with IBD exacerbation [29 pts with Crohn's disease (CD) and 67 pts with ulcerative colitis (UC)] and 15 healthy controls. Fecal NGAL was determined by ELISA in fecal specimens. We used a set of Human Lipocalin-2 / NGAL ELISA, production BioVendor, Czech Republic. The average age of patients with CD was 36 ± 2 years, UC - 37 ± 1 years, in the control group - 31 ± 2 years. Severity of CD was assessed by CDAI: mild CD was seen in 7 (24%), moderate – 13 (45%), severe – 9 (31%), in UC by Mayo score: mild – 22 (33%), moderate – 28 (42%), severe – 17 (25%).

Results: Fecal NGAL level was increased in active IBD – 4122 [861; 6850] ng/ml (p < 0.05) compared with healthy controls – 181 [169; 720] ng/ml. Level of NGAL in UC was higher – 4668 [1298; 7792] ng/ml (p < 0.05) than that in CD – 2688 [200; 5710] ng/ml. In severe CD NGAL was higher – 5908 [2860; 12920] ng/ml than in moderate CD – 2236 [172; 4236] ng/ml (p < 0.05) and mild CD 896 [200; 3828] ng/ml (p < 0.05). In severe UC fecal NGAL was higher – 6044 [4605; 9632] ng/ml than in moderate UC – 4963 [2198; 7780] ng/ml (p > 0.05) and mild CD – 2194 [786; 4668] ng/ml(p < 0.05).

Fecal NGAL correlated with clinical parameters of IBD: in CD with the severity of fever (r=0.40; p<0.05), in UC with the stool consistency (r=0.25; p<0.05) and the weight loss (r=0.27; p<0.05). Also in CD NGAL levels had a significant correlation with the C-reactive protein (r=0.70; p<0.05), in UC – with the erythrocyte sedimentation rate (r=0.44; p<0.05).

ROC-analysis defined the threshold of fecal NGAL as a marker for determining an active phase of inflammation in IBD - 1144 ng/ml, to which were empirically determined sensitivity of 72%, specificity of 100%, and AUC – 0.88. Thus, the findings suggest that studied indicator have high resolution in identifying IBD.

Conclusion: The fecal level of NGAL significantly increased during flare of IBD with a high sensitivity, specificity and AUC. The concentration of NGAL in UC was higher than that in CD. NGAL correlated with the severity and activity of CD.

Disclosure of Interest: None declared

P0341 HETEROGENEITY IN THE ENDOSCOPIC MANAGEMENT OF CROHN’S DISEASE ASSOCIATED STRICTURES: RESULTS FROM AN INTERNATIONAL INFLAMMATORY BOWEL DISEASE SPECIALIST SURVEY

D. Bettenworth¹, R. Lopez², P. Hindryckx³, B. G. Levesque⁴, F. Rieder⁵⁶

¹Department of Medicine B, University Hospital Münster, Münster, Germany, ²Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, United States, ³Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium, ⁴Division of Gastroenterology, University of California, San Diego, ⁵Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, ⁶Department of Gastroenterology, Hepatology & Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, United States

Contact E-mail Address: dominik.bettenworth@ukmuenster.de

Introduction: Crohn’s disease (CD) is frequently complicated by a stricturing phenotype, leading to intestinal obstruction. Endoscopic balloon dilation (EBD) represents a widely used approach for the management of intestinal strictures in CD. Available evidence in this area, however, is limited. Aim of this study was to depict heterogeneity of endoscopic management of CD associated strictures among international CD specialists to identify common treatment standards.

Aims & Methods: A questionnaire was developed by the gastroenterology faculties of the Cleveland Clinic and the University Hospital Muenster and placed on an online platform. Participants were asked about their endoscopic experience, practice setting and number of EBD annually. Two case scenarios as well as technical practice parameters were investigated. The questionnaire was distributed through the IOIBD, ECCO, PROVIT and national IBD networks. Statistical analysis was performed using appropriate tests.

Results: 126 subjects from 15 countries (11.1% colorectal surgeons; 40.5% subspecialized in interventional endoscopy; endoscopy experience 15.2 ± 8.2 years) completed the survey. The maximal length of dilated stricture was 4.5 ± 1.7 cm. The most commonly used balloon size was graded 15-18 mm with a dilation time of 1.7 ± 1.2 minutes. While 87.2% of participants favored the use of EBD for anastomotic strictures, only 58.6% did so in case of naïve strictures. Only 35.7% of physicians dilated actively inflamed strictures. Concomitant therapies employed were injection of steroids (11.2%) or infliximab (1.7%), cutting techniques (5.2%), and stent placement (0.9%). 89.7% used serial dilations in the same patient over time.

Heterogeneity in practice existed among the participants: Interventional endoscopists were more likely to dilate only clinically symptomatic strictures (p=0.046). Surgeons favored surgical treatment of de novo ileocaecal strictures (p=0.026 compared to gastroenterologists) and reported a shorter stricture length being amendable to EBD (p=0.045). They more frequently used concomitant therapies (p=0.001). Traversal of the colonoscope after dilation was more frequent in academic hospitals followed by community hospitals and then private practice (p=0.013). Balloon inflation time was longest in Europe and shortest in North America (p=0.041). Operator experience increased the likelihood of EBD in actively inflamed strictures (p=0.002), maximum length of stricture and maximum balloon size (p=0.001).

Conclusion: EBD is a widely used treatment approach for stricturing CD. However, individual selection of strictures appropriate for EBD and the technical approach differ widely based on individual background of the operator, experience level and practice setting. Therefore, evidence-based consensus guidelines for the practical management of EBD are highly desirable.

Disclosure of Interest: None declared

P0342 ENDOTHELIAL MICROPARTICLES AS PLASMA BIOMARKERS OF ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES

D. Cibor¹, D. Owczarek¹, K. Salapa², T. Mach¹

¹Gastroenterology, Hepatology & Infectious Diseases, ²Bioinformatics and Telemedicine, Jagiellonian University Medical College, Krakow, Poland

Contact E-mail Address: dorota.cibor@gmail.com

Introduction: Endothelial dysfunction plays a pivotal role in the development of inflammatory bowel diseases (IBD). Activity of endothelial cells can be determined by the use of both physical and biochemical methods as well. One of the recently discovered plasma biomarkers are microparticles derived form the endothelium. They can play an important role in interactions with circulating cells and the vascular wall.

Aims & Methods: The study aimed to assess level of circulating microparticles in IBD patients as well their correlation with clinical status.

Sixty IBD patients aged 18-65 (32 Crohns’s disease (CD), 28 ulcerative colitis (UC)) and 60 sex- and age-matched healthy controls were included into the study. Levels of circulating endothelial microparticles were measured and related to disease phenotype, clinical and biochemical activity.

Results: In UC group (14F and 14M) mean microparticles level was 122 +/- 70/ul of plasma and in CD group (17F and 15M) - 144 +/- 40/ul of plasma. We found statistical differences between active and inactive UC group (140 +/- 60/ul vs 96 +/- 64/ul, p < 0.05) as well between active and inactive CD group (176 +/- 66/ul vs 102 +/- 56/ul, p< 0.01). There were no differences between inactive disease and healthy controls (p > 0.05) Microparticles level correlated weekly positively with CD activity (r=0.35) but not with UC activity (r=0.12).

Conclusion: Elevated level of circulating endothelial microparticles confirms the role of endothelial dysfunction in IBD patients. It is also an indicator of the disease activity, however this relationship is more pronounced in CD patients.

Disclosure of Interest: None declared

P0343 DISPARITY OF CROHN’S DISEASE ACTIVITY BETWEEN AN OUTPATIENT VISIT AND AT HOME IS ASSOCIATED WITH POOR CLINICAL OUTCOMES; RESULTS OF A WEB-BASED, SELF-REPORTING SYMPTOM DIARY FOR CROHN’S DISEASE

E. S. Kim¹, B. I. Jang², K. O. Kim², S. W. Jeon³, E. Y. Kim⁴, K. B. Cho¹, K. S. Park¹, C. H. Yang⁵, on behalf of Daegu-Gyeongbuk Gastrointestinal Study Group (DGSG)

¹Internal Medicine, Keimyung University School of Medicine, ²Internal Medicine, Yeungnam University College of Medicine, ³Internal Medicine, Kyungpook National University School of Medicine, ⁴Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, ⁵Internal Medicine, Dongguk University School of Medicine, Gyeongju, Republic of Korea

Contact E-mail Address: dandy813@hanmail.net

Introduction: As Crohn’s disease (CD) is characterized by its unpredictable clinical course, the ideal approach for the assessment of disease activity would be real-time monitoring of patient's symptoms.

Aims & Methods: The aim of this study was to identify discordance of patients’ symptoms between on routine clinic visits and at home using a web-based self-reporting Crohn’s disease symptom diary (CDSD) and to evaluate its impact on clinical outcomes. CDSD consisted of 5 clinical parameters based on the Harvey-Bradshaw Index, which could easily be recorded online, by using CDSD website (www.cdsd.or.kr). Between February 2012 and October 2014 patients with CD were invited to record their symptoms at home at least once a week and on the routine outpatient clinic visit as well. We identified the patients who showed disparity of disease activity between on the regular hospital visits and at home and evaluated clinical outcomes of these patients such as biologic use, abdominal surgery, and unscheduled visits with Kaplan-Meier analysis. Risk factors related with unscheduled visits were also assessed.

Results: Among 280 patients with CD invited, 155 (male 109, age 26.17 ± 8.19 years) who recorded their symptoms weekly basis at least for consecutive 3 months were included in the study. Fifty four patients (34.8%) showed different disease activities between at home and on the hospital. Cumulative risk of abdominal surgery (P=0.046) and unscheduled visits (P < 0.001) was significantly higher in this disparity group than concordance group. Disparity in symptoms (HR 3.61, 95% CI 1.68-7.77, P=0.001), steroid exposure (HR 2.71 95% CI 1.02-7.24, P=0.046) and use of biologics (HR 3.92, 95% CI 1.81-8.49, P=0.001) were independent risk factors associated with unscheduled visits to the hospital.

Conclusion: Disparity in disease activity is considerable in patients with CD and is related with the negative clinical outcome. More attention should be paid to identifying patients with this unstable activity using a real-time monitoring tool.

Disclosure of Interest: None declared

P0344 ACCURACY OF CALPROTECTIN AND NGAL IN EVALUATING HISTOLOGICAL SUB-CLINICAL INFLAMMATION IN ULCERATIVE COLITIS (ACERTIVE- STUDY)

F. Magro¹, on behalf of GEDII, S. Lopes¹, R. Coelho¹, J. Cotter², T. Meira³, P. Andrade¹, H. T. Sousa⁴, M. Salgado⁵, P. Caldeira⁶, C. Camila-Dias⁷, P. Borralho⁵, K. Geboes⁸, J. Afonso⁹, F. Carneiro¹⁰

¹Gastrenterology, Centro Hospitalar São João, Porto, ²Gastrenterology, Centro Hospitalar do Alto Ave, Guimarães, ³Gastrenterology, Hospital Garcia de Orta, Almada, ⁴Gastrenterology, Centro Hospitalar do Barlavento Algarvio, Portimão, ⁵Gastrenterology, Centro Hospitalar do Porto, Porto, ⁶Gastrenterology, Hospital de Faro, Faro, ⁷CIDES-Department of Health Information and Decision Sciences, Faculty of Medicine, Porto, Portugal, ⁸GI Pathology, KU Leuven, Belgium, Belgium, ⁹Pharmacology, Faculty of Medicine University of Porto, ¹⁰Pathology, Centro Hospitalar São João, Porto, Portugal

Contact E-mail Address: fernandomagro65@gmail.com

Introduction: Fecal calprotectin (fcal) has been reported as an important biomarker of endoscopic healing in ulcerative colitis (UC).

Aims & Methods: We assessed accuracy of fcal − evaluated by 2 assays, Quantum Blue (QB) and automated fluoroimmunoassay (EliA) − and fecal Neutrophil gelatinase-associated lipocalin (NGAL), aiming to predict the histological activity in UC patients without clinical activity according to partial Mayo score. Histological evaluation was performed by 3 independent pathologists.

Results: 369 UC patients were recruited, left side colitis (57%) or pancolitis (43%). The Geboes scoring system was used to evaluate the histological activity, and 22% of UC patients were scored as ≥3.1. In 29% of the cases there was endoscopic activity (Mayo 1, 2 or 3). In 20% of the patients, basal plasmocytosis was observed, diffuse in 5% of the cases. Histological activity was observed in patients with Mayo score 0 (11%) and Mayo scores 1 and 2 (43% and 86%, respectively). In asymptomatic UC patients, high fcal was observed in 25% evaluated by QB (>250 ug/g), 20% evaluated by EliA (>150 ug/g), and in 31% of the cases there was a high level of NGAL(>12 ug/g). The median values of fcal and NGAL in patients with histological remission were: QB-81.5 ug/g (IQ: 30-224); EliA- 29 ug/g (IQ: 6.8-99.5); NGAL-8.5 ug/g (IQ: 4.7-15.1). The negative predictive value (VPN) and accuracy for histological activity (Geboes ≥ 3.1) was the following for different assays: QB (>250 ug/g): VPN-83%, accuracy-70%; EliA (>150 ug/g): VPN-84%, accuracy-73%; for NGAL (>12 ug/g), the VPN-83% and accuracy 63%, respectively. The predictability of histological remission evaluated by the area under curve was: QB: 0.72 (CI:0.66-0.78); EliA 0.71 (CI:0.65-0.76); NGAL 0.66 (CI:0.58-0.74).

Conclusion: Approximately 30% of asymptomatic UC patients had high biomarkers levels and histological or endoscopic activity. Calprotectin and NGAL are reliable and accurate biomarkers to detect persistent histological inflammation in asymptomatic UC patients.

Disclosure of Interest: None declared

P0345 CHANGES OF ADALIMUMAB TROUGH LEVELS CORRELATE WITH BODY COMPOSITION PARAMETERS

A. A. Csontos¹, A. Molnár², Z. Piri¹, B. Katona¹, K. Farkas³, T. Molnár³, P. Miheller¹

¹2nd Department of Internal Medicine, Semmelweis University, ²mandrea.mccbe@gmail.com, Semmelweis University, Budapest, ³First Department of Medicine, University of Szeged, Szeged, Hungary

Contact E-mail Address: csontosagnesanna@gmail.com

Introduction: Anti-TNF alfa adalimumab (ADA) is a well-established treatment in inflammatory bowel disease (IBD). The drug is administered subcutaneously in an uniform dose regardless of body weight. Monitoring ADA trough levels may be recommended in the future to optimize and personalize therapy and to improve efficacy. Our aim was to explore whether body composition parameters influence ADA trough levels and its variability.

Aims & Methods: Eighteen IBD patients initiating ADA treatment were included in our study. Induction therapy was started with ADA 160/80mg at weeks 0/2, then 40mg every other week as a maintenance. ADA trough levels were measured at week 6 and 12. Bioelectrical impedance analysis (BIA) was carried out and body composition was measured by InBody 720 body analyser device right before starting biological therapy. Body composition indexes were derived from the computed values (fat-free mass index [FFMI], skeletal muscle index [SMI] and body fat mass index [BFMI]) of BIA. Body surface area was calculated by using DuBois-DuBois formula.

Results: According to our findings ADA trough levels had not differ significantly at week 6 and 12 (8.00 ± 2.9µg/mL vs. 7.73 ± 3.14µg/mL). Three of the patients (6.7%) had suboptimal ADA trough levels, only one of them were detected to have antibodies, he was excluded from further investigations. The changes of adalimumab trough levels correlated with body surface area (r=−0.682; p=0.002). We also found moderate correlation between the variability of trough levels and muscle parameters (FFMI: r=−0.494, p=0.045, SMI: r=−0.508, p=0.038). However the changes of ADA trough levels did not correlate with BIA fat parameters nor the proportion of extracellular and intracellular fluid (BFMI: r=−0.099 and extracellular/intracellular water r=0.089)

Conclusion: The results of our pilot study suggest that body surface area and body muscle parameters may influence the constancy of ADA trough levels. The findings arise the question whether adalimumab dosage offerd to be adjusted to body surface area or body compostion in the future. To confirm this suspicion larger patients population and their ADA trough levels should be investigated.

Disclosure of Interest: None declared

P0346 INDICATORS OF SUBOPTIMAL THERAPY AMONG CROHN’S DISEASE PATIENTS TREATED WITH TUMOR NECROSIS FACTOR ANTAGONISTS: RESULTS FROM A MULTINATIONAL STUDY

A. Armuzzi¹, J. O. Lindsay², R. Mody³, B. Bokemeyer⁴, J. P. Gisbert⁵, L. Peyrin-Biroulet⁶, G. C. Nguyen⁷, J. Siebenaler⁸, Ö. Åkerborg⁹, M. Smyth¹⁰

¹IBD Unit, Complesso Integrato Columbus, Catholic University, Rome, Italy, ²Department of Gastroenterology, Barts Health NHS Trust, London, United Kingdom, ³Takeda Pharmaceuticals International, Inc., Deerfield, United States, ⁴Gastroenterology Practice, Minden, Germany, ⁵Hospital Universitario de La Princesa, IIS-IP and CIBEREHD, Madrid, Spain, ⁶CHU de Nancy - Hôpital Brabois, Vandœuvre-lès-Nancy, France, ⁷Mount Sinai Hospital, Toronto, Canada, ⁸Mapi, Milton, United States, ⁹Mapi, Stockholm, Sweden, ¹⁰Takeda Development Centre Europe Ltd, London, United Kingdom

Contact E-mail Address: reema.mody@takeda.com

Introduction: Crohn’s disease (CD) patients treated with tumor necrosis factor antagonists (anti-TNFs) may require therapy changes over time, which may be considered as indicators of suboptimal therapy.

Aims & Methods: A multinational, multicentre, retrospective, chart review study was conducted to assess the indicators of suboptimal therapy among adult CD patients receiving their first anti-TNF [infliximab (IFX) or adalimumab (ADA)] between June 2009 and June 2011 (index therapy). The indicators of suboptimal therapy during 2-year follow up were: anti-TNF dose-escalation (assessed >4 months after index to allow for initial dose adjustments), augmentation with a non-biologic drug, discontinuation of first anti-TNF, switching to another anti-TNF and CD-related surgery. Percentages of patients with each indicator type and ≥1 indicator by country for each anti-TNF drug are summarized descriptively.

Results: The study included 657 CD patients with mean age (SD) of 39.2 (13.2) years, 51% females, 51% with moderate to severe CD at index, 44% and 56% on ADA and IFX respectively, and 71% on combination therapy with a non-biologic drug. Overall, 56% of CD patients had ≥1 indicator of suboptimal therapy, 20% of patients had dose escalation, 18% needed augmentation with a non-biologic, 29% discontinued first anti-TNF, and 17% underwent a CD-related surgery. Of those who discontinued (N=183), 70% switched to another anti-TNF. Patients with indicators of suboptimal therapy for each country by the anti-TNF are shown in the Table.

Abstract number: P0346 Table.

Indicators of suboptimal anti-TNF therapy among CD patients during 2-year follow up

Indicator of suboptimal anti-TNF therapy	Canada		France		Germany		Italy		Spain		UK		Overall
	IFXN= 40	ADAN=24	IFXN=50	ADAN=26	IFXN=43	ADAN=66	IFXN=75	ADAN=69	IFXN=66	ADAN=78	IFXN=91	ADAN=29	IFXN=365	ADAN=292
%
≥1 of the following Indicators	75.0	50.0	74.0	65.4	34.9	62.1	60.0	44.9	42.4	41.0	64.8	62.1	58.6	51.71
Anti-TNF Dose escalation	40.0	41.7	32.0	23.1	9.3	18.2	18.7	14.5	9.1	11.5	17.6	31.0	19.7	19.2
Augmentation with a  non-biologic drug1	20.0	12.5	32.0	15.4	11.6	22.7	24.0	13.0	7.6	10.3	17.6	34.5	18.6	16.8
Discontinuation of first anti-TNF2	27.5	16.7	36.0	30.8	20.9	31.8	34.7	21.7	25.8	17.9	38.5	13.8	31.8	22.6
Switching to another anti-TNF3	15.0	12.5	30.0	19.2	11.6	22.7	22.7	18.8	18.2	12.8	28.6	3.4	22.2	16.1
CD-related Surgery	20.0	16.7	24.0	15.4	7.0	16.7	21.3	18.8	13.6	15.4	16.5	13.8	17.3	16.4

¹ Augmentation defined as any new additions or increase in dose/frequency of the concurrent non-biological therapy with anti-TNF therapy. ²Discontinuation as reported in patients’ medical charts and by excluding patients that reported discontinuing first anti-TNF because it was effective. ³Switch defined as a subset of discontinuation patients who initiated another anti-TNF therapy over the course of the follow-up period.

Conclusion: In this large multinational cohort, over half of the CD patients had ≥1 indicator of suboptimal anti-TNF therapy. Predominant indicators included dose escalation, discontinuation and switching to another anti-TNF.

STUDY FUNDED BY TAKEDA PHARMACEUTICALS INTERNATIONAL, Inc.

Disclosure of Interest: A. Armuzzi Financial support for research: MSD, Lecture fee(s): Abbvie, Astra-Zenaca, Chiesi, Ferring, Hopira, MSD, Otsuka, Takeda, Zambon, Consultancy: Abbvie, Hospira, Liily, MSD, Mundipharma, Pfizer, Sofar, Takeda, J. Lindsay Conflict with: Served as a speaker, a consultant and advisory board member for or has received research funding from MSD, Abbvie, Hospira, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Vifor Pharma, Atlantic Health care, Actavis (Warner Chilcott), and Tillotts, R. Mody Conflict with: Employee of Takeda Pharmaceuticals International, Inc., B. Bokemeyer Financial support for research: Abbvie, Ferring, UCB, Lecture fee(s): Abbvie, Ferring, MSD, Merckle, Falk, HLR, UCB, Consultancy: Abbvie, MSD, Shire, Ferring, UCB, Hospira, Takeda, Movetis, J. Gisbert Conflict with: Served as a speaker, a consultant and advisory member for or has received research funding from MSD, Abbvie, Hospira, Kern Pharma, Takeda, Janssen, Pfizer, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Vifor Pharma, L. Peyrin-Biroulet Lecture fee(s): Abbvie, MSD, Janssen, Takeda, Mitsubishi, Consultancy: Abbvie, MSD, Janssen, Takeda, Hospira, Celltrion, Biogaran, G. Nguyen Conflict with: Advisory board for Janssen and Abbvie, J. Siebenaler Conflict with: Employee of Mapi, a company hired to conduct the study by Takeda Pharmaceuticals International, Inc., Ö. Åkerborg Conflict with: Employee of Mapi, a company hired to conduct the study by Takeda Pharmaceuticals International, Inc., M. Smyth Conflict with: Employee of Takeda Development Centre Europe Ltd, London, United Kingdom

P0347 LONG-TERM ADALIMUMAB EFFICACY IN STEROID-DEPENDENT CROHN’S DISEASE PATIENTS: A PROSPECTIVE “REAL LIFE” STUDY

A. Orlando¹, S. Renna¹, M. Cappello², R. Di Mitri³, F. Mocciaro³, M. Mazza², M. Giunta⁴, M. Mendolaro², A. Craxì², M. Cottone¹

¹DiBiMis, Division of Internal Medicine, “Villa Sofia-Cervello” Hospital, Palermo University, ²DiBiMis, Department of Gastroenterology and Hepatology, Palermo University, ³Gastroenterology and Endoscopy Unit, ARNAS Civico-Di Cristina-Benfratelli Hospital, ⁴Gastroenterology and Endoscopy Unit, “Villa Sofia-Cervello” Hospital, Palermo, Italy

Contact E-mail Address: fmocciaro@gmail.com

Introduction: Adalimumab (ADA) is effective in the induction and maintenance of steroid-free remission in patients (pts) with steroid-dependent Crohn’s disease (CD). We have already reported data on efficacy and prognostic factors of response of ADA (80/40 or 160/80 mg every other week followed by 40 mg every other week) in 110 steroid-dependent pts. At week 6, 91% of pts have had a clinical benefit (remission: 45.5%, response: 45.5%). At the end of the follow-up (mean 14.6 months), 80.9% of responders have maintained the clinical benefit (remission: 64.5%, response: 16.4%). Only higher induction regimen was related to remission at week 6. At the end of the follow-up, none of the variables were associated with remission. Up to now no data are available on long term efficacy of ADA in the setting of steroid dependent pts.

Aims & Methods: All the 110 pts treated in the previous study were followed up until April 2015 and the following variables were evaluated at the end of the follow up: maintenance of clinical benefit, ADA discontinuation, dose exalation, switch to another biologic, surgical treatment and side effects.

Results: At the end of the follow up (mean 74.16 ± 10.3 months) only 5 pts resulted lost during the follow-up. Concerning the remaining 105 pts, 42 pts (40%) obtained the clinical benefit: 1) 37/42 (88%) were still in maintaining treatment with ADA at the dosage of 40 mg sc (of these pts 13/37 [35%] received a weekly maintaining treatment); 2) 5/37 (12%) discontinued ADA due to mucosal healing. Sixty-three pts (60%) discontinued ADA: 1) 50/63 (79%) for lost of clinical benefit (20 of these 50 pts were operated on [40%]); 2) 6/63 (10%) for side effects; 3) 5/63 (8%) for severe endoscopic activity despite clinical response; 4) 2/63 (3%) died for reason not related to ADA treatment. Among pts who discontinued ADA 24/63 (38%) were then effectively switched to another biologic (infliximab or golimumab). At univariable analysis we did not find variables related to the treatment outcomes. ADA was well tolerated. Only one pts developed an acute leukaemia after 2 years of ADA discontinuation.

Conclusion: This long-term “real-life” prospective study showed that ADA is a good maintaining treatment in steroid dependent CD but 1/3 of them needed dose escalation to maintain clinical benefit. The rate of long term side effects that needed treatment discontinuation is quite low. In pts intolerant to or with lost of response to ADA a switch to another biologic is an effective opportunity.

Disclosure of Interest: None declared

P0348 THE COMBINATION OF MESENCHYMAL STROMAL CELLS AND INFLIXIMAB INCREASES THE ANTI-INFLAMMATORY EFFECT OF THE TREATMENT OF ULCERATIVE COLITIS

O. Knyazev¹, A. Kagramanova¹

¹Department of Inflammatory Bowel Disease, Moscow Clinical Research Center, Moscow, Russian Federation

Contact E-mail Address: oleg7@bk.ru

Introduction: Mesenchymal stromal cells (MSCs) have a high immunosuppressive potential. Concentration of azathioprine, methotrexate, 6-mercaptopurine, infliximab (IFX) no effect on the viability, differentiation, phenotype MSC and ability to suppress proliferation of peripheral blood mononuclear cells. These results are important for the clinical application of MSCs in combination with immunomodulators and anti-TNF-α therapy. However, little is known about the effectiveness of the combined use of MSC and immunomodulatory drugs in the treatment of IBD. Aim. Assess the clinical and endoscopic efficacy of combination therapy of ulcerative colitis (UC) with concurrent use MSC and IFX.

Aims & Methods: 1st group patients (n=28) who were administered MSCs twice a month at intervals of 1 week + after 6 months from the date the first administration of MSCs. 2nd group patients with UC (n=26) received IFX. 3rd group of patients with UC (n=10) received MSC and IFX. Follow-up was 24 months. To assess the clinical activity of ulcerative colitis, we used the index Rachmilevitz, to assess the endoscopic activity. Analysis of the effectiveness of different biologic therapy of patients with UC after 2, 6 and 12 months of therapy. Initial level clinical activity index before treatment was in group 18.98 ± 0.38 points in the 2nd - 9.1 ± 0.4, and 3rd, respectively, - 9.1 ± 0.6, the level of endoscopic activity index before treatment was in the 1st group 7.46 ± 0.2 points, in the 2nd - 7.62 ± 0.16, in the 3rd - 7.6 ± 0.4 (p > 0.05).

Results: After 2 months of clinical activity index decreased significantly from baseline in 1st group to 1.53 ± 0.24 points in the 2nd - to 1.27 ± 0.12, in the 3rd to 1.1 ± 0.17 points (p > 0.05 between groups). After 6 months of clinical activity index was in group 11.64 ± 0.24 points in the 2nd - 1.35 ± 0.14 points, 3rd - 0.7 ± 0.15 points, which was significantly lower than in the 1st and 2nd groups (p < 0.05). After 12 months of clinical activity index was in group 11.68 ± 0.8 points in the 2nd - 1.62 ± 0.16 points, 3rd - 0.5 ± 0.16 points, which was significantly lower than in the 1st and 2nd groups (p < 0.05). Index Mayo after 2 months decreased significantly from baseline in the 1st, 2nd and 3rd groups of up to 1.57 ± 0.24, 1.65 ± 0.25, 1.22 ± 0.2 scores (p < 0.05), respectively. After 6 months the index Mayo in 1st group was 1.6 ± 0.24 points, in the 2nd - 1.65 ± 0.19, in the 3rd - 1.1 ± 0.2 points. After 12 months, the index of the Mayo patients 3rd group was 0.8 ± 0.2 points, which was significantly lower (p < 0.05) than in 1st group - 1.46 ± 0.22 points and 2nd - 1.43 ± 0.1, groups of patients with UC.

Conclusion: Combined biological therapy of inflammatory bowel disease contributes to more stable clinical and endoscopic remission compared to monotherapy with biological agents after 1 years.

Disclosure of Interest: None declared

P0349 COMPARATIVE ASSESSMENT OF THE SAFETY OF STEM CELLS AND STANDARD ANTI-INFLAMMATORY THERAPY OF CROHN'S DISEASE

O. Knyazev¹, A. Kagramanova¹, A. Parfenov¹

¹Department of Inflammatory Bowel Disease, Moscow Clinical Research Center, Moscow, Russian Federation

Contact E-mail Address: kagramanova@me.com

Introduction: Mesenchymal stromal cells (MSCs) are now widely used in clinical studies with various diseases, providing a positive effect due to the immunomodulatory and paracrine mechanisms. However, the safety profile of these cells remains unproved.

Objective: To compare the safety of treatment of the patients with Crohn's disease (CD), receiving comprehensive anti-inflammatory therapy with the application of MSCs standard therapy with 5-aminosalicylic acid (5-ASA), glucocorticosteroids (GSCs) and immunosuppressive agents (IS).

Materials and methods.

Aims & Methods: Within the period from 2008 to 2014 the system transplantation of allogenic MSCs was carried out in 64 patients with CD. 47 patients were included in the first group, the average monitoring time averaged 62 ± 4 months. 19 of them (40.4%) were men and 28 (59.26%) women. The average age was 30.4 ± 1.2 years. 124 patients with CD, who received standard anti-inflammatory therapy with 5-ASA and GCSs, were included in the second, control group. Out of them 56 (45.2%) were men and 68 (54.8%) women. The average age was 36.8 ± 1.5 years. The patients, who received anti-cytokine therapy, were not included in this group. The safety of the used therapy was assessed by the presence of complications, arising during the observation, infectious complications, exacerbation of chronic inflammatory diseases, serious infectious complications, a malignant transformation, a lethal outcome.

Results: In the first group of patients with CD the development of non-severe infectious complications or exacerbation of chronic inflammatory diseases were registered in 7 patients out of 56, that totaled 12.5%, in the second in 14 (16.7%) patients out of 84. When comparing the two groups, no differences were found in the risk of the development of infectious complications and exacerbation of chronic inflammatory diseases on the background of the standard anti-inflammatory CD therapy or with the introduction of the MSCs (RR-0.75, 95% Cl 1.5-23.58; x²-0.16; p=0.66). Severe infectious complications (pneumonia, pleurisy, activation of latent TB) in the first group were detected in 1 patient (1.8%) out of 56, and in the second group in 5 (5.9%) out of 84. When comparing the two groups no differences in the risk of this type of complications were also found (RR-0.3; 95% Cl 0.04-2.5; x²-0.59; p=0.44). Colorectal cancer was registered only in one she-patient from the first group (1.8%). The time between the introduction of the MSCs and diagnosed colon cancer was 10 days. In the second group of patients over the 5 years of follow-up, malignant transformation was observed in 4 (4.8%) patients out of 84 (RR-0.5, 95% Cl 0.05-4.96; x²-0.01; p=0.97). Within 5 years of follow-up in the first and second groups of patients, fatal outcomes were registered on one occasion in each group, 1.8% and 1.2% respectively (RR-1.5, 95% Cl 0.1-23.49; x²-0.19, p=0.66).

Conclusion: The analysis did not reveal any differences in the development of severe infectious complications, exacerbation of chronic inflammatory diseases, serious infectious complications of malignant transformations and deaths in patients with CD, who received the MSCs and the standard anti-inflammatory therapy.

Disclosure of Interest: None declared

P0350 FINAL THIOPURINE METABOLITE LEVELS AND SHUNTER STATUS CAN BE PREDICTED AFTER SIX WEEKS OF THIOPURINE THERAPY–BIOCHEMICAL OUTCOMES FROM THE EATME STUDY

A. B. Friedman¹, J. D. Brookes¹, M. G. Ward¹, H. Belinda¹, L. N. Nihill¹, J. Reynolds¹

¹Gastroenterology, The Alfred Hospital, Melbourne, Australia

Contact E-mail Address: a.friedman@alfred.org.au

Introduction: Dosing of thiopurines [azathioprine (AZA) and mercaptopurine (MP)] in the management of IBD has been based upon patient weight. However, it appears unreliable in predicting final levels of thiopurine metabolites. This leads to suboptimal clinical outcomes because of under- and over-dosing, and ‘shunting’ in 15% where toxic 6-methylmercaptopurine (6MMP) is preferentially produced over the efficacious 6-thioguianine nucleotides (6TGN), with 6MMP:6TGN ratio ≥20.

Aims & Methods

Aims: 1. To determine prospectively the clinical value of timing of measurement of thiopurine metabolites during dose-escalating regimen of thiopurine initiation in a consecutive cohort of IBD patients being initiated on a thiopurine. 2. To determine if the 6MMP:6TGN ratio changes during thiopurine dose escalation.

Methods: In this single-centre, prospective, open label study patients were commenced on either a daily dose of 50 mg AZA or 25 mg MP (physician discretion). Doses increased fortnightly by 50 mg for AZA or 25 mg for MP until target was achieved, aiming for 2–2.5 mg/kg for AZA and 1–1.5 mg/kg for MP. Hematology, CRP and liver function tests were performed fortnightly to monitor toxicity, and thiopurine metabolites were measured fortnightly until steady-state was achieved, but these results were not used for dosing decisions. Clinical and biochemical outcomes were recorded. Landmark analyses of shunter status used logistic regression models. Metabolite levels were analysed using linear regression models.

Results: 64 patients (52 Crohn’s, 11 ulcerative colitis and 1 IBD-U) were enrolled. Final metabolite outcomes were: 11 (17%) patients were shunters, 27 (42%) were underdosed (6TGN level of <260 pmol/8X10⁸ RBCs), 5 (8%) patients’ levels were supratherapeutic (6TGN >450) and only 21 (33%) were therapeutic. 6MMP:6TGN ratios escalated over time in shunters, but not in others. After 2 weeks of therapy, a 6MMP:6TGN ratio above 9 (p=0.058) was suggestive of shunting, while after 6 weeks, a ratio ≥12 (95% CI 7–28, p=0.01) was predictive of shunting. 6TGN levels at week 2 (median 106, range 0–328) predicted final 6TGN outcomes (median 282, range 50–746, r=0.681, p<.001) and 6MMP levels at week 2 (median 236, range 0-2163) predicted final 6MMP outcomes (median 1301, range 62–14600, r=0.835, p<.001). 23% of MP and 14% of AZA patients were shunters (p=0.395). At no time point did levels predict an adverse event to thiopurines. No correlation was detected between the weight-based dose of thiopurines and final ratios (r=−0.277), 6TGN (r=0.044) and 6MMP (r=−0.193) levels (all p values >.10).

Conclusion: 6MMP:6TGN ratios increase during dose escalation in shunters only. Patients with a 6MMP:6TGN ratio 12 or above after 6 weeks should be considered for optimisation with allopurinol rather than waiting until 12 weeks of therapy. Weight-based dosing of thiopurines should no longer be used in standard practice.

Disclosure of Interest: None declared

P0351 IMMUNOGENICITY OF THE BIOSIMILAR INFLIXIMAB: INTERIM RESULTS FROM A PROSPECTIVE NATIONWIDE COHORT

B. Lovász¹, K. B. Gecse¹¹, K. Farkas², J. Banai³, L. Bene⁴, B. Gasztonyi⁵, P. A. Golovics¹, T. Kristof⁶, L. Lakatos⁷, P. Miheller⁸, F. Nagy², K. Palatka⁹, M. Papp⁹, Á. Patai¹⁰, Á. Salamon¹, T. Szamosi³, Z. Szepes², T. G. Tóth¹², Á. Vincze¹³, T. Molnár², P. Lakatos¹

¹First Department of Medicine, Semmelweis University, Budapest, ²First Department of Medicine, University of Szeged, Szeged, ³Department of Gastroenterology, Military Hospital – State Health Centre, ⁴First Department of Medicine, Peterfy Hospital, Budapest, ⁵Second Department of Medicine, Zala County Hospital, Zalaegerszeg, ⁶Second Department of Medicine, BAZ County Hospital, Miskolc, ⁷Department of Medicine, Csolnoky Ferenc Regional Hospital, Veszprem, ⁸Second Department of Medicine, Semmelweis University, Budapest, ⁹Department of Gastroenterology, University of Debrecen, Debrecen, ¹⁰Department of Medicine, Markusovszky Hospital, Szombathely, ¹¹Department of Gastroenterology, Tolna County Teaching Hospital, Szekszárd, ¹²Department of Gastroenterology, János Hospital, Budapest, ¹³First Department of Medicine, University of Pécs, Pécs, Hungary

Contact E-mail Address: krisztina.gecse@gmail.com

Introduction: Biosimilar infliximab CT-P13 received EMA approval in June 2013 for all indications of the originator product. We aimed to prospectively evaluate the immunogenicity of the biosimilar infliximab in IBD in a nationwide, multicentre cohort.

Aims & Methods: Demographic data were collected and a harmonized monitoring strategy was applied. Clinical and biochemical activity were evaluated at week 14. Trough level (TL) and anti-drug antibody (ADA) concentration were measured by ELISA (LT-005, Theradiag, France) at baseline and before each anti-TNF administration during the induction treatment.

Results: 141 consecutive IBD patients (90 CD patients and 51 UC patients) were included in the present cohort. 29% (26 and 3%) of CD patients and 22% (16 and 6%) of UC patients had received previous anti-TNF (infliximab and adalimumab) therapy. None of the patients had received infliximab within 12 months prior to initiation of the biosimilar infliximab. 62/61% of CD/UC patients received concomitant immunosuppressives at baseline. Mean TLs were 0, 19.2, 9.1. and 3.4μg/ml at weeks 0, 2, 6 and 14. There was a tendency towards lower TLs at week 2 and 6, but not at week 14 in patients with previous infliximab exposure compared to infliximab naive patients. This was coupled with higher ADA positivity. There was no significant difference in the remission and response rates between patients with or without previous anti-TNF exposure. 6 patients had allergic reactions during induction treatment, of which 4 patients had received previous infliximab treatment.

Conclusion: Patients with previous exposure to the originator infliximab had a tendency towards lower early TL coupled with ADA positivity. Although there were no significant difference in efficacy, patients with previous infliximab exposure were more likely to develop allergic reactions.

Disclosure of Interest: None declared

P0352 OPERATING PROPERTIES OF DIFFERENT PATIENT-REPORTED OUTCOME ENDPOINTS COMBINED WITH ENDOSCOPIC EVALUATION: DATA FROM EXTEND

B. Feagan¹², W. Sandborn³, P. Rutgeerts⁴, B. G. Levesque³, R. Khanna¹², A. M. Robinson⁵, B. Huang⁵, Q. Zhou⁵, H. Read⁵, K. Wallace⁵, A. Lacerda⁵, R. Thakkar⁵

¹Univ of Western Ontario, ²Robarts Research Inst, London, Canada, ³UCSD, La Jolla, United States, ⁴Univ of Leuven, Leuven, Belgium, ⁵AbbVie, N Chicago, United States

Contact E-mail Address: anne.robinson@abbvie.com

Introduction: Patient reported outcome (PRO) components of the Crohn’s disease (CD) Activity Index (CDAI) are being explored as clinical remission (CR) endpoints,¹ as are composite measures of endoscopic remission (ER) plus CR as outcome measures in CD trials.

Aims & Methods: To explore the use of different definitions of CR, based on CDAI stool frequency (SF) and abdominal pain (AP) components, and composite endpoints on efficacy estimations in the mucosal healing study EXTEND.² Three CR definitions were explored in patients (pts) from EXTEND: 1) CDAI <150, 2) sum of 7 day weighted SF/AP PRO components of CDAI <69 (PRO2 <69), and 3) average (avg) daily SF ≤1.5 and avg daily AP score ≤1.0, both not worse than baseline (BL) (SF ≤1.5 and AP ≤1.0). Pooled data from 4 CD adalimumab (ADA) trials were used to identify the threshold for PRO2 which correlated best with CDAI <150 in pts with elevated BL avg daily SF ≥2.5 or AP score ≥2.0, and the combined SF/AP definition was based on a recent report.¹ In EXTEND, adults with moderate to severe CD received induction ADA 160/80 mg at weeks (wks) 0/2. At wk 4, pts were randomized to ADA 40 mg every other wk or placebo (PBO) to wk 52. Pts (N=104) with BL avg daily SF ≥2.5 or AP score ≥2.0 and Simple Endoscopic Score for CD (SES-CD) ≥6 (or ≥4 for pts with isolated ileal disease) by central read were analyzed at wks 12 and 52. Endpoints assessed were the 3 CR definitions, ER (SES-CD ≤4 and at least 2 point reduction from BL, by central read), and composite ER and CR for each remission definition.

Results: ER was achieved by 37.3% and 15.1% of ADA- and PBO-treated pts, respectively, at wk 12 (Δ22.2%, p=0.01); wk 52 values were 27.5% and 1.9% (Δ25.6%, p < 0.001), respectively. Compared with ER, composite endpoints generally showed diminished effect sizes for ADA vs PBO at wks 12 and 52 (Table). Overall, composite endpoint effect sizes were similar to or slightly less than CR effect sizes. At wk 52, the SF/AP definition was associated with the lowest rates of remission in both PBO and ADA groups, and the lowest effect size of all CR definitions.

Table. Effect size for various definitions of remission (NRI)

Abstract number: P0352

	CDAI <150			PRO2 <69			SF ≤1.5 and AP ≤1.0#
	ADAN=51	PBON=53	Δ	ADAN=51	PBON=53	Δ	ADAN=51	PBON=53	Δ
Clinical endpoint alone, wk 12	47.1	32.1	15.0	51.0	32.1	18.9	33.3	13.2	20.1*
Clinical endpoint plus endoscopic remission, wk 12	23.5	11.3	12.2	27.5	11.3	16.1*	19.6	1.9	17.7**
Clinical endpoint alone, wk 52	35.3	9.4	25.9**	35.3	9.4	25.9**	21.6	7.5	14.0
Clinical endpoint plus endoscopic remission, wk 52	25.5	0	25.5***	23.5	0	23.5***	15.7	0	15.7**

Δ, Difference between treatment groups (effect size)

^#Each score not worse than BL

Nonresponder imputation (NRI) was used for pts with missing data and those who moved to open-label ADA

*p < 0.05; **p < 0.01; ***p < 0.001 by Fisher’s exact test

Conclusion: Use of a composite endpoint (endoscopic plus symptomatic remission) led to diminished effect sizes compared to the endoscopic definition alone. Use of new endpoints should consider the ability of the endpoint to distinguish drug effect from PBO.

Disclosure of Interest: B. Feagan Financial support for research: Centocor, Merck, UCB, Abbott, Lecture fee(s): Centocor, Merck, Abbott, Consultancy: Centocor, Merck, UCB, Abbott, Millenium/Takeda, Genentech/Hoffman LaRoche, Neovacs, Merck/Serono, Bristol Myers Squibb, Robarts, Tillotts, Pfizer, Falk Pharma, W. Sandborn Financial support for research: AbbVie, BMS, Genentech, GSK, Janssen, Millennium, Novartis, Pfizer, P&G, Shire, UCB, Lecture fee(s): AbbVie, BMS, Janssen, Consultancy: AbbVie, ActoGeniX, AGI, Alba, Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas, Athersys, Atlantic Healthcare, Aptalis, BioBalance, Boehringer-Ingelheim, BMS, Celgene, Celek, Cellerix SL, Cerimon, ChemoCentryx, CoMentis, Cosmo, Coronado, Cytokine, Eagle, Eisai, Elan, EnGene, Eli Lilly, Enteromedics, Exagen, Ferring, Flexion, Funxional, Genzyme, Genentech, Gilead, Given, GSK, Human Genome Sciences, Ironwood, Janssen, KaloBios, Lexicon, Lycera, Meda, Merck, MerckSerono, Merck & Co, Millennium, Nisshin Kyorin, Novo Nordisk, NPS, Optimer, Orexigen, PDL, Pfizer, P&G, Prometheus, ProtAb, Purgenesis, Receptos, Relypsa, Salient, Salix, Santarus, Shire, Sigmoid, Sirtris, S.L.A., Targacept, Teva, Therakos, Tillotts, TxCell, UCB, Viamet, VBL, Warner Chilcott, P. Rutgeerts Lecture fee(s): Centocor, Merck and UCB Pharma, Consultancy: AbbVie, Bristol-Myers Squibb, Centocor, Merck, Millennium Pharmaceuticals Inc. (now Takeda) and UCB Pharma, B. Levesque Consultancy: AbbVie, Takeda, Nestle Health Sciences, and Prometheus Labs, R. Khanna Consultancy: AbbVie, Takeda, Janssen, A. Robinson Conflict with: AbbVie employee, may own AbbVie stock and/or options, B. Huang Conflict with: AbbVie employee, may own AbbVie stock and/or options, Q. Zhou Conflict with: AbbVie employee, may own AbbVie stock and/or options, H. Read Conflict with: AbbVie employee, may own AbbVie stock and/or options, K. Wallace Conflict with: AbbVie employee, may own AbbVie stock and/or options, A. Lacerda Conflict with: AbbVie employee, may own AbbVie stock and/or options, R. Thakkar Conflict with: AbbVie employee, may own AbbVie stock and/or options

P0353 THE LONG-TERM EFFECT OF ANTI-TNF ALPHA THERAPY ON SERUM LIPID PROFILE AND ATHEROGENIC INDEX IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES

C. Kalkan¹, F. Karakaya¹, E. A. Kalkan¹, A. E. Tüzün¹, Z. B. Gençtürk², M. Törüner¹, H. Çetinkaya¹, I. Soykan¹

¹Gastroenterology, ²Biostatistics, Ankara University, Ankara, Turkey

Contact E-mail Address: isoykan@medicine.ankara.edu.tr

Introduction: Cardiovascular morbidity appears to be increased in inflammatory bowel diseases (IBD). Tumor necrosis factor (TNF) is a pivotal proinflammatory cytokine in inflammatory diseases and causes deterioration of the lipid profile in inflammatory conditions. It is postulated that in patients with IBD, proinflammatory cytokine TNFα can alter lipid profile causing dyslipidemia that promotes atherogenesis. However, previous reports investigating the effect of anti-TNFα blockers on lipid profile in IBD patients showed conflicting results.

Aims & Methods: Therefore, the aim of this study was to identify long-term effect of anti-TNFα therapy on lipid profile and atherogenic index (AI) in patients with IBD followed-up to 36 months (mos). A total of 56 patients diagnosed as having IBD [44 Crohn’s disease (CD) and 12 colitis ulcerosa (CU)] and treated with anti-TNFα agents (33 received adalilumab, 23 received remicade) were evaluated by means of serum lipid profile and serum total cholesterol, triglyceride, LDL-c and HDL-c were measured within 1 month before the first dose of anti-TNFα agent and then after six-month periods. AI was also calculated by dividing total cholesterol to HDL-c before biologic agent and then every six-month periods. Patients followed-up less then 12 mos, with diabetes, receiving antilipidemic agents were not included into the study.

Results: The median follow-up period was 26.1 months. With anti-TNFα treatment, serum cholesterol level was found to be increased compared to baseline (163.1 vs 179 mg/dL, p=0.01), triglyceride level increased at 24^th mos compared to baseline (118 vs 152.1 mg/dL, p < 0.001), LDL level increased at 36^th mos compared to baseline (92 vs 110.71 mg/dL, p=0.022), and HDL level did not show any significant change during follow-up period. As for AI, AI significantly increased at 36^th mos compared to baseline (3.84 vs 4.09, p < 0.001). There were no significant differences by means of lipid profile and AI between patients with CD vs UC and patients receiving adalilumab vs remicade.

Conclusion: Significant changes were observed in cholesterol and LDL levels of patients with IBD on anti-TNFα after 36 mos of treatment. A significant increase in AI was also observed in this study. Therefore, anti-TNFα treatment might affect lipid profile and AI which may contribute to cardiovascular morbidity. AI can contribute significantly in the prediction of coronary artery disease risk especially when lipid profile is not markedly deranged.

Disclosure of Interest: None declared

P0354 VALPROIC ACID REGULATES MUCOSAL CYTOKINE PRODUCTION, APOPTOSIS PATHWAYS AND HISTONE ACETYLATION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES

C. Felice¹², A. Lewis¹, R. Jeffery¹, T. Kumagai¹, A. Nijhuis¹, H. Thompson¹, A. Armuzzi², J. O. Lindsay¹, A. Silver¹

¹Centre for Digestive Diseases, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, United Kingdom, ²IBD Unit, Internal Medicine and Gastroenterology, Complesso Integrato Columbus, Catholic University, Rome, Italy

Contact E-mail Address: c.felice@qmul.ac.uk

Introduction: Novel therapeutic strategies are required for inflammatory bowel diseases (IBD), as significant numbers of patients do not respond to current treatments. Oral administration of valproic acid (VPA) has been shown to reduce acute and chronic intestinal inflammation in animal models of colitis.¹ VPA inhibits histone deacetylase (HDAC) enzymes² involved in the epigenetic regulation of apoptosis, cell differentiation and cytokine production. No data are available about the effect of VPA on human intestinal inflammation.

Aims & Methods: The aim of this study was to determine whether VPA induces histone hyperacetylation, influences mucosal cytokine production and impacts on apoptosis pathways in patients with IBD. Intestinal biopsies from IBD patients undergoing routine colonoscopy at the Royal London Hospital were collected and cultured with VPA (0.05 mM, 0.5 mM and 5 mM) or control media for 24 hours. Total RNA was extracted and the mRNA levels of cytokines and markers of apoptosis assessed by qPCR. The cytokine protein levels in culture supernatant were quantified using Luminex assays (IFNγ, IL-1b, IL-23, IL-6, TNFα and IL-10) and ELISA (IL-6). To confirm the proposed mechanism of action, the effect of VPA on histone-3-acetylation levels was assessed using immunofluorescence microscopy. SPSS version 22 was used for statistical analysis.

Results: Intestinal biopsies from 17 IBD patients (7 Crohn’s disease, 10 ulcerative colitis) were collected and cultured with or without VPA. Relative to control, culturing with the highest concentration of VPA (5 mM) was associated to a significant reduction in IL-6, IL-22 and IL-10 mRNA expression (p=0.001, p=0.01 and p=0.001, respectively, Wilcoxon test). VPA did not affect TNFα and IFNγ mRNA expression. Culture with VPA 5mM reduced IL-6, TNFα and IL-10 protein levels in biopsy culture supernatants (p=0.005, p=0.002 and p=0.002, respectively, Wilcoxon test). No differences were found in the level of IFNγ, IL-1b and IL-23 protein. IL-6 concentration in the culture supernatant was confirmed to be significantly reduced by VPA 5 mM using ELISA (p=0.02, Wilcoxon test). The reduction in cytokine expression was associated with a significant reduction in Bcl-3 mRNA expression (p=0.008) and an increase in Caspase-9 gene expression (p=0.001, Wilcoxon test), demonstrating a stimulation of pro-apoptotic pathways. The percentage of H3-acetylated positive cells was significantly higher in biopsies treated with VPA 5 mM compared with untreated (n=4; p=0.002, t test).

Conclusion: VPA, a broad-acting HDAC inhibitor, regulates cytokine production, increases the activity of pro-apoptotic pathways and induces histone-3 hyperacetylation in intestinal mucosa of IBD patients. These results encourage further investigation of the therapeutic role of HDAC inhibition in patients with IBD.

Disclosure of Interest: C. Felice Financial support for research: ECCO Fellowship 2015; IG-IBD educational grant 2014-2015, Lecture fee(s): AbbVie, Consultancy: MSD, A. Lewis: None declared, R. Jeffery: None declared, T. Kumagai: None declared, A. Nijhuis: None declared, H. Thompson: None declared, A. Armuzzi Financial support for research: MSD, Lecture fee(s): AbbVie, Astrazeneca, Chiesi, Ferring, Hospira, MSD, Otsuka, Takeda, Zambon, Consultancy: AbbVie, Hospira, MSD, Lilly, Mundipharma, Pfizer, Sofar, Takeda, J. Lindsay Financial support for research: MSD, Shire, Lecture fee(s): AbbVie, Atlantic Healthcare, Ferring, MSD, Takeda, Warner Chilcott, Consultancy: AbbVie, Atlantic Healthcare, Ferring, MSD, Takeda, Warner Chilcott, A. Silver: None declared

P0355 FISTULIZING PERIANAL CROHN'S DISEASE TREATMENT WITH INFLIXIMAB ALONE OR COMBINED WITH SURGERY - RESULTS OF ONE YEAR FOLLOW-UP

C. Bernardes¹, D. Carvalho¹, P. Russo¹, J. Saiote¹, J. Ramos¹

¹Hospital de Sto António dos Capuchos, Lisbon, Portugal, Lisbon, Portugal

Contact E-mail Address: carlosfbernardes@gmail.com

Introduction: Infliximab (IFX) is effective in the treatment of Fistulizing Perianal Crohn's Disease (FPCD); however, data regarding its long-term efficacy is still limited. Combined biological and surgical treatment may offer some advantages in selected patients.

Aims & Methods: The aim of this study was to assess IFX's efficacy, alone or combined with surgery, in patients with FPCD. We conducted an analysis of prospective and systematic clinical registries of patients in whom FPCD was the indication for IFX therapy, either alone or following surgery. Examination under anesthesia was executed prior to the initiation of treatment. Clinical registries were performed at weeks (wk) 0, 2, 6, 14, 30 and 54 of IFX therapy and included evaluation of Perianal Disease Activity Index (PDAI) and Fistula Drainage Assessment (FDA). Partial response (PR) was defined as at least 50% reduction in the PDAI value and at least 50% reduction in the number of draining fistulas or at least 50% healing of the perianal post-surgical wound in those who underwent surgery. Complete response (CR) was defined as a PDAI score ≤ 4 and closure of all draining fistulas or complete healing of the perianal post-surgical wound. Loss of response (LR) was defined by any increase in PDAI, by the recrudescence of draining fistulas, by the occurrence of any other perianal complication or the need for additional therapy.

Results: Thirty-six patients (19 males; average age 34 ±14 years, range 16-75 years) with FPCD initiated IFX therapy. Seventeen (47%) patients underwent previous surgical procedure: abscess drainage (n=9), abscess drainage and fistulotomy (n=6) or fistulotomy/fistulectomy (n=2); seton placement was performed in 7. At baseline (wk0), median PDAI value was 12. At wk14, 83% of patients achieved response (PR 30%, CR 53%), with an average decrease of 8.3 in PDAI score from baseline. At wk54 response was 75% (PR 19%, CR 56%); LR occurred in 7 patients (19%), all of them maintaining lower PDAI score than at baseline (average decrease of 5.6 from wk0). Biological therapy was suspended in 2 patients because of serious adverse reaction; there were no cases of perianal abscess development during follow-up.

Conclusion: Therapy with IFX, combined with surgery when appropriated, achieved early clinical response and healing in FPCD, maintaining response in 75% (partial response 19%, complete response in 56%) of patients at the 52nd week.

Disclosure of Interest: None declared

P0356 LONG-TERM OUTCOMES OF ADALIMUMAB THERAPY IN ULCERATIVE COLITIS PATIENTS BY PRIOR ANTI-TNF EXPOSURE

C. Taxonera¹, E. Iglesias², F. Muñoz³, M. Calvo⁴, M. Barreiro-de Acosta⁵, D. Busquets⁶, X. Calvet⁷, A. Rodriguez⁸, R. Pajares⁹, J. P. Gisbert¹⁰, P. Lopez-Serrano¹¹, J. L. Perez-Calle¹¹, A. Ponferrada¹², C. de la Coba¹³, F. Bermejo¹⁴, M. Chaparro¹⁰, C. Alba¹, D. Olivares¹, I. Fernandez-Blanco¹⁵

¹H Clinico San Carlos and IdISSC, Madrid, ²H Reina Sofia, Cordoba, ³H Virgen Blanca, Leon, ⁴H Puerta de Hierro, Madrid, ⁵H Clinico de Santiago, Santiago de Compostela, ⁶HU Josep Trueta, Girona, ⁷Parc Tauli, Sabadell, ⁸H Clinico de Salamanca, Salamanca, ⁹H Infanta Sofia, ¹⁰H la Princesa and CIBEREHD, ¹¹H Fundacion Alcorcon, ¹²H Infanta Leonor, Madrid, ¹³H de Cabueñes, Gijon, ¹⁴H de Fuenlabrada, ¹⁵H Moncloa, Madrid, Spain

Contact E-mail Address: carlos.taxonera@salud.madrid.org

Introduction: The impact of anti-TNF exposure on the outcomes of adalimumab (ADA) therapy in ulcerative colitis (UC) patients is not well known. The aim of this study was to compare the long-term outcomes of ADA in UC patients according to previous anti-TNF use.

Aims & Methods: This was a retrospective multicentre cohort study evaluating UC patients who were primary responders to ADA induction therapy and who advanced to a maintenance regimen. We compared the outcomes of the cohorts of anti-TNF-naïve patients versus anti-TNF-experienced patients. The primary endpoints were the cumulative probabilities of ADA failure-free survival and colectomy-free survival. ADA failure was defined as withdrawal of the drug due to intolerance or complete loss of response. We also assessed the need for ADA dose escalation during follow up. Predictors of event-free survival were estimated using Cox proportional hazard regression analysis.

Results: Of the 184 UC primary ADA responders included, 116 (63%) had previous anti-TNF use. During a median follow-up of 16 months (interquartile range [IQR] 7-39), 69 patients (37%) had ADA failure. Anti-TNF-naïve patients had a significantly lower adjusted rate of ADA failure compared to anti-TNF-experienced patients (hazard ratio [HR] 0.65; 95% CI: 0.52-0.80; p < 0.001). After a median follow-up of 21 months (IQR 12-47), 22 patients (12%) needed colectomy. Median time to colectomy was 10 months (IQR 4-18). Anti-TNF-naïve patients had a significant 74% reduction in the need for colectomy (HR 0.26; 95% CI: 0.10-0.65; p=0.004). Seventy-six patients (41%) required escalation to weekly ADA dosing. The median time to escalation was 4 months (IQR 2-9). Anti-TNF-naïve patients had a significantly lower adjusted rate of the need for escalation (HR 0.38; 95% CI: 0.21-0.69; p=0.002). Patients who needed escalation had a significantly higher adjusted rate of ADA failure (HR 1.78; 95% CI: 1.08-2.94; p=0.02) and need for colectomy (HR 3.13; 95% CI: 1.22-8.03; p=0.02).

Conclusion: In this real–life cohort of primary ADA responders with UC, 63% of patients maintained sustained clinical benefit and 88% of patients avoided colectomy. Anti-TNF-naïve patients had better outcomes in the long-term, with a significant reduction in the rates of ADA dose escalation, ADA failure and colectomy.

Disclosure of Interest: C. Taxonera Financial support for research: MDS; Abbvie, Lecture fee(s): MDS; Abbvie, E. Iglesias: None declared, F. Muñoz: None declared, M. Calvo: None declared, M. Barreiro-de Acosta: None declared, D. Busquets: None declared, X. Calvet: None declared, A. Rodriguez: None declared, R. Pajares: None declared, J. Gisbert: None declared, P. Lopez-Serrano: None declared, J. L. Perez-Calle: None declared, A. Ponferrada: None declared, C. de la Coba: None declared, F. Bermejo: None declared, M. Chaparro: None declared, C. Alba: None declared, D. Olivares: None declared, I. Fernandez-Blanco: None declared

P0357 LONG-TERM TREATMENT WITH FERRIC MALTOL IS EFFECTIVE AND WELL TOLERATED IN CORRECTING IRON DEFICIENCY ANEMIA IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: RESULTS FROM A PHASE-3 OPEN-LABEL STUDY

C. Schmidt¹, T. Ahmad², Z. Tulassay³, D. C. Baumgart⁴, B. Bokemeyer⁵, S. Howaldt⁶, A. Stallmach¹, C. Büning⁷, on behalf of AEGIS Study Group

¹Clinic of Internal Medicine IV, Jena University Hospital, Jena, Germany, ²University of Exeter Medical School, Exeter, United Kingdom, ³Department of Medicine, Semmelweis University of Medicine, Budapest, Hungary, ⁴Division of Gastroenterology and Hepatology, Department of Medicine, Charité Medical School, Humboldt-University of Berlin, Berlin, ⁵Gastroenterology Practice, Minden, ⁶Division of Inflammatory Bowel Disease, Hamburg Institute of Research, Hamburg, ⁷Department of Internal Medicine, Hospital Waldfriede, Berlin, Germany

Contact E-mail Address: carsten.schmidt@med.uni-jena.de

Introduction: Iron deficiency anemia (IDA) is frequently seen in inflammatory bowel disease (IBD). Oral iron supplementation with ferrous products (OFP) is linked to possible gastrointestinal side effects and disease exacerbation in some IBD-patients. Recently, ferric maltol provided rapid and clinically meaningful improvement in Hb and showed a favorable safety profile during a pivotal 12 week study [1]. The following multicenter phase-3 open-label extension study evaluated the long-term efficacy and safety of ferric maltol.

Aims & Methods: Initially, adult patients with quiescent or mild-to-moderate ulcerative colitis or Crohn’s disease, mild-to-moderate IDA, and failure on previous OFP received oral ferric maltol capsules (30 mg twice a day) or placebo for 12 weeks. Following the randomised, double-blind phase of the study, patients were eligible to receive open-label ferric maltol for up to an additional 52 weeks.

Results: In total, 111 subjects received ferric maltol for up to 64 weeks. Hb continued to rise in those previously treated with ferric maltol (mean from baseline 3.07 (SD 1.46) g/dL at week 64, n=36). Increases were also observed in former placebo-treated subjects (mean 1.87 (SD 1.20) g/dL by week 24 (12 weeks of treatment; n = 53), and 2.19 (SD 1.61) g/dL by week 64 (52 weeks of treatment; n=36). The proportion of subjects with normal Hb concentration continued to rise for those treated with ferric maltol initially (week 12: 71%, week 64: 86.1%; ) and for those switching to ferric maltol (week 12: 15.1% and 83.3% at week 64). Ferritin rose from 8.4 ug/L at baseline (n=128) to 24.9 ug/L at 12 weeks (n=112) and 68.9 ug/L at 64 weeks (n=36). In total, 80% of subjects reported at least one AE, however, only 24% of subjects reported an AE considered to be treatment related. 18 subjects (16%) discontinued due to adverse events, but only 8 (7%) of these were evaluated as treatment related AEs. The most common AEs were abdominal pain (16%), diarrhoea (14%), nasopharyngitis (18%), flatulence (8%), and arthralgia (8%). No worsening of IBD scores (SCCAI, CDAI) was observed during the entire study.

Conclusion: Long-term treatment with ferric maltol resulted in a continuous rise of mean Hb, with Hb normalisation in more than 80% of patients. Ferritin levels increased when treatment was continued past 12 weeks. The adverse event profile in the open label phase confirmed the benign safety profile of oral ferric maltol and the feasibility of long-term treatment.

Disclosure of Interest: None declared

P0358 SUBSTANTIAL HISTOLOGICAL IMPROVEMENT FOLLOWING HAEMOPOETIC STEM CELL TRANSPLANTATION FOR CROHN'S DISEASE

C. Sharratt¹, C. Hawkey¹, M. Allez², M. Clark¹, M. Labopin³, J. Lindsay⁴, E. Ricart⁵, G. Rogler⁶, J. Satsangi⁷, D. Farge⁸, P. Kaye⁹, on behalf of, and the. ASTIC Investigators

¹Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, United Kingdom, ²Dept of Gastroenterology, APHP Hopital Saint Louis, ³CEREST-TC/EBMT Paris Study Office, Hopital Saint-Antoine, Paris, France, ⁴Centre for Digestive Diseases, Barts & The London School of Medicine & Dentistry, London, United Kingdom, ⁵Gastroenterology Dept, Hospital Clinic, Barcelona, Spain, ⁶Div Gastroenterology & Hepatology, University of Zurich, Zurich, Switzerland, ⁷Gastro-Intestinal Unit, University of Edinburgh, Edinburgh, United Kingdom, ⁸Internal Medicine & Vascular Disease Unit & Autoimmune Disease Party of European Society for Blood & Marrow Transplantation, AP-HP Hopital Saint-Louis, Paris, France, ⁹Dept of Histopathology, University Hospital, Nottingham, United Kingdom

Contact E-mail Address: cj.hawkey@nottingham.ac.uk

Introduction: Haemopoietic stem cell transplantation (HSCT) leads to complete regression of endoscopic signs of Crohn's disease in about one third of patients, implying an alteration in the natural history of Crohn's disease. We investigated whether these substantial changes were also seen histologically.

Aims & Methods: Patients with impaired quality-of-life from active Crohn's disease not amenable to surgery despite treatment with at least 3 immunosuppressive agents all underwent stem cell mobilisation before randomisation to immuno-ablation followed by unselected cyclophosphamide-based conditioning and HSCT after one month (Early HSCT) or one-year (Delayed HSCT). They underwent full ileocolonoscopy at baseline and after one and two years. Endoscopic involvement and activity were assessed using the Simple Endoscopic Score of Crohn’s disease (SES CD) in which a value of zero means no evidence of active or inactive Crohn's disease in any examined segment of the ileum or colon. In 17 patients segments were biopsied systematically for blinded histological assessment, using ECCO-approved scales for intensity and diffuseness of acute and chronic inflammation, granulomas, ulceration, distortion and metaplasia.

Results: There was a strong correlation between endoscopic findings and histology (Table).

% Normal Histology	Endoscopy: Normal	Involved	p
Ileum	78%	25%	0.001
Right Colon	90%	36%	<0.0001
Transverse Colon	83%	38%	0.003
Left Colon	93%	24%	<0.0001
Rectum	73%	27%	0.001

The % of colonic biopsy samples that were histologically normal rose from 39% (baseline) to 50% at 1 year and 78% at 2 years after Early HSCT (p=0.039). In patients undergoing Delayed HSCT values were 52% (baseline), 50% 1 year after mobilisation only and 75% after a further year following delayed HSCT (p=0.329). Improvements were mainly due to reduction or regression of acute and chronic inflammatory changes.

Conclusion: Blinded histological assessments fortify the evidence that HSCT can have a profound objective benefit in Crohn's disease.

Disclosure of Interest: None declared

P0359 FOUR-YEAR EFFICACY AND SAFETY OF AZATHIOPRINE TREATMENT IN THE MAINTAINANCE OF STEROID-FREE REMISSION IN INFLAMMATORY BOWEL DISEASE PATIENTS

C. Cassieri¹, R. Pica², E. V. Avallone¹, G. Brandimarte³, M. Zippi², P. Crispino¹, D. De Nitto², C. Corrado¹, P. Vernia¹, P. Paoluzi¹, E. S. Corazziari¹

¹Internal Medicine and Medical Specialties, Sapienza “University", ²Unit of Gastronterology and Digestive Endoscopy, Sandro Pertini Hospital, ³Internal Medicine, Cristo Re Hospital, Rome, Italy

Contact E-mail Address: claudio.cassieri@libero.it

Introduction: Azathioprine (AZA) and thiopurine are widely used for induction and maintenance of remission in patients steroid-dependent with inflammatory bowel disease (IBD). The treatment must be withdrawn in 5-30% of patients due to the occurrence of adverse events.

Aims & Methods: Aim of this study has been to investigate its efficacy and safety in maintaining steroid-free remission in steroid dependent IBD patients four year after the institution of treatment. Data from consecutive IBD outpatients referred in our Institution, between 1985-2013, were reviewed and all patients treated with AZA were included in this retrospective study. AZA was administered at the recommended dose of 2–2.5 mg/kg. Blood chemistry was analysed before administration of the drug, every 10-15 days for the first 3 months and then every 1-2 months following the institution of treatment.

Results: Out of 2556 consecutive IBD outpatients visited in the index period, AZA was prescribed to 376 patients, 198 (52.7%) were affected by Crohn's disease (CD) and 178 (47.3%) by ulcerative colitis (UC). One hundred and four patients with a follow-up <48 months were excluded from the study. Two hundred and seventy-two patients were evaluated, 146 (53.7%) with CD and 126 (46.3%) with UC. One hundred and forty-nine (54.8%) were male and 123 (45.2%) female (average age of 33.56 ± 14.34 SD years, range 14-74 y.). Four year after the institution of treatment, 149 (54.8%) patients still were in steroid-free remission (89 CD vs 60 UC, 61% and 47.6%, respectively, p=0.0288), 71 (26.1%) had a relapse requiring retreatment with steroids (42 UC vs 29 CD, 33.4% and 19.8%, respectively, p=0.0130), 52 (19.1%) discontinued the treatment due to side effects (28 CD vs 24 UC, 19.2% and 19%, respectively). Loss of response from 1^st to 4^th year of follow-up was low, about 17%.

Conclusion: Four years after the onset of treatment 55% of patients did not require further steroid courses. After the first year loss of response was low in three subsequent years. In the present series the maintenance of steroid-free remission was significantly higher in CD than in UC patients. The occurrence of side effects leading to the withdrawal of AZA treatment has been low.

Disclosure of Interest: None declared

P0360 MAINTENANCE ANTI-TNF THERAPY HAS A BENEFICIAL EFFECT ON BONE MINERAL DENSITY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

C. Kiat¹, R. Abdelhaq¹, A. Malik¹, Y. Bailey¹, N. Breslin¹, D. McNamara¹, S. Veerappan¹, B. Ryan¹

¹Department of Gastroenterology, The Adelaide & Meath Hospital, Dublin, Ireland

Contact E-mail Address: clifford.kiat@gmail.com

Introduction: It has been well established that patients with inflammatory bowel disease (IBD), both ulcerative colitis (UC) and Crohn’s disease (CD), are at increased risk of osteoporosis. Prior studies have shown that both Adalimumab and Infliximab have beneficial effects on bone metabolism in patients with CD in the short term. However, no data is available on the longer term effect of maintenance anti-TNF on bone mineral density (BMD) in patients with IBD

Aims & Methods: We aim to evaluate the medium to long-term impact of maintenance anti-TNF therapy on BMD in patients with IBD. The study was a retrospective observational cohort study of patients with IBD who were commenced on anti-TNF therapy (either Infliximab or Adalimumab). All patients underwent BMD measurement (DEXA scan) prior to commencement of anti-TNF therapy. BMD was then measured at variable intervals following commencement of therapy, with a minimum of one year prior to repeat BMD. A detailed chart review of patients’ demographics, disease phenotypes and concomitant treatments was performed. This review is on- going and to date data for 30 patients has been analysed. A paired t-test was performed to evaluate the changes in BMD in patients on Adalimumab or Infliximab.

Results: To date, data for 30 patients has been analysed. There were 18 female patients and the mean age for the cohort was 45 years (SD +/- 12.8). 28 patients have CD and 2 have UC. 16 patients were on maintenance Infliximab and 12 on Adalimumab. Mean T score prior to commencement of biologic therapy was -1.68 (SD +/- 1.10). The mean T-score at follow up DEXA was -1.41 (SD +/- 1.15). The mean interval between BMD measurements was 2.9 years (SD +/- 1.5). There was a significant improvement in T score between initial and follow up BMD, P=0.039 (CI:-0.531,-0.014)

Conclusion: In this study, we show a significant improvement in T scores of IBD patients following commencement of maintenance anti-TNF therapy.

Disclosure of Interest: None declared

P0361 INTERFERON-γ RELEASE ASSAY VERSUS TUBERCULIN SKIN TEST IN PATIENTS WITH MODERATE-TO-SEVERELY ACTIVE ULCERATIVE COLITIS: RESULTS FROM THE PURSUIT UC PROGRAM

C. Marano¹, E. C. Hsia¹, S. Xu², W. Sandborn³, P. Rutgeerts⁴

¹Immunology, ²Biostatistics, Janssen R & D, LLC, Spring House, ³Gastroenterology, University of California San Diego, La Jolla, United States, ⁴Gastroenterology, University of Hospital Gasthuisberg, Leuven, Belgium

Contact E-mail Address: cmarano@its.jnj.com

Introduction: To report the results of an interferon-γ release assay (IGRA) versus standard tuberculin skin test (TST) as a screening tool for latent TB infection in patients with ulcerative colitis (UC) in PURSUIT.

Aims & Methods: UC patients with moderately to severely active UC were screened for latent TB using the standard TST and the IGRA to assess eligibility for entry into the induction studies of golimumab (PURSUIT-SC [C0524T17]and PURSUIT-IV [C0524T1]Any patient with a newly identified positive finding for TB on a diagnostic test in whom there was no evidence of active TB was permitted to enter provided appropriate treatment for latent TB was initiated before or at the time of the first dose of study agent. TST was performed according to the Mantoux method, using 5 tuberculin units (TU) of purified protein derivative (PPD) standard or 2 TU of PPD RT-23. The TST was deemed positive for latent TB infection according to the local country guidelines for defining an immunosuppressed host or, in the absence of local guidelines, according to the presence of induration ≥5mm. The IGRA used to screen for latent TB was the QuantiFERON-TB Gold In-Tube test. Overall IGRA and TST results were assessed. The impact of prior BCG vaccination and concomitant medication (ie corticosteroids and/or immunomodulators) on outcome was also assessed.

Results: In this analysis, 1283 patients had both IGRA and TST screening prior to GLM treatment. Among these patients, 8.7% had at least one test yielding positive findings for latent TB, including 6.2% with positive results only by TST, 3.7% with positive results only by IGRA, and 1.2% with positive results on both tests. The rate of indeterminate results for TB on IGRA was 7.7%. Agreement between the TST and IGRA results, measured by the kappa coefficient, was 0.135 (95% confidence interval [95% CI] 0.050-0.220; p=0.028). Among patients with positive IGRA findings, 31.3% had positive TST results. Among patients with positive TST findings, 19.0% had positive IGRA results. Overall, 501 (40.5%) of 1283 patients had previously received BCG vaccine; among this vaccinated group, the rate of positivity for latent TB by TST was 10.4% vs 5.0% for IGRA positivity. Among patients who had not received BCG vaccine, the rate of positivity by TST was 1.9% vs 2.8% for IGRA positivity. When IGRA was repeated in patients whose results were initially indeterminant, the majority of patients (67.0%) were IGRA negative on repeat whereas the number of patients whose results were positive was 5.3%; IGRA remained indeterminate for 27.7%. Overall, 2.1% tested indeterminate on first and repeat screening. Concomitant corticosteroid and/or immunomodulator use did not appear to have an impact on results.

Conclusion: Results of this comparison of IGRA and TST in a large cohort of patients with UC suggest that the IGRA provides greater specificity and possibly greater sensitivity than the TST in patients with moderate to severe UC.

Disclosure of Interest: C. Marano Conflict with: Employee Janssen R & D, LLC, E. Hsia Conflict with: Employee Janssen R & D, LLC, S. Xu Conflict with: Employee Janssen R & D, LLC, W. Sandborn Financial support for research: Janssen R & D, LLC, P. Rutgeerts Financial support for research: Janssen R & D, LLC

P0362 THE EXPENSES OF ACADEMIC INPATIENT CARE OF INFLAMMATORY BOWEL DISEASE PATIENTS ARE ALMOST DOUBLE COMPARED WITH AVERAGE ACADEMIC GASTROENTEROLOGY AND HEPATOLOGY CASES AND NOT FULLY RECOVERED BY DIAGNOSIS-RELATED GROUP (DRG) PROCEEDS

D. C. Baumgart¹, M. le Claire²

¹Department of Medicine, Division of Gastroenterology and Hepatology, ²Enterprise Controlling, Charité Medical Center - Medical School of the Humboldt-University of Berlin, Berlin, Germany

Contact E-mail Address: daniel.baumgart@charite.de

Introduction: Crohn’s disease (CD) and ulcerative colitis (UC) challenge economies worldwide. Detailed diagnosis-related group (DRG) data of academic inpatient care for inflammatory bowel disease (IBD) patients in Europe is unavailable.

Aims & Methods: IBD was identified through ICD-10 K50 and K51 code groups. We took an actual costing approach, compared expenditures to G-DRG and non-DRG proceeds and performed detailed cost center and type accounting to identify coverage determinants.

Results: Of all 3093 hospitalized cases at our department 164 were CD and 157 UC inpatients in 2012. On average, they were 44.1 (CD 44.9 UC 43.3 all 58) years old, stayed 10.1 (CD 11.8 UC 8.4 vs. all 8) days, carried 5.8 (CD 6.4 UC 5.2 vs. all 6.8) secondary diagnoses, received 7.4 (CD 7.7 UC 7 vs. all 6.2) procedures, had a higher cost weight (CD 2.8 UC 2.4 vs. all 1.6) and required more intense nursing. Their care was more costly (means: total cost IBD 8477€CD 9051€UC 7903€vs. all 5078€). However, expenditures were not fully recovered by DRG proceeds (means: IBD 7413€, CD 8441€, UC 6384€vs all 4758€). Here, we discovered substantial disease-specific mismatches in cost centers and types and identified the medical ward personnel and materials budgets to be most imbalanced. Non-DRG proceeds were almost double (IBD 16.1% vs. all 8.2%), but did not balance deficits at total coverage analysis, that found medications (antimicrobials, biologics and blood products), medical materials (mostly endoscopy items) and in CD also non-medical intrastructure costs to contribute most to the deficit.

Conclusion: DRGs threaten sophisticated, academic care for the neediest of all IBD patients.

Disclosure of Interest: None declared

P0363 LONG-TERM OUTCOMES OF ULCERATIVE COLITIS PATIENTS ON MONOTHERAPY MAINTENANCE TREATMENT WITH THIOPURINES: PRELIMINARY DATA

D. Pugliese¹, P. M. Ferraro², A. Aratari³, G. Margagnoni³, R. Monterubbianesi⁴, C. Felice¹, A. Papa¹, L. Guidi¹, A. Kohn⁴, C. Papi³, A. Armuzzi¹

¹IBD UNIT, ²Nephrology, Complesso Integrato Columbus Catholic University, ³U.O.C. Gastroenterololy & Hepatology, San Filippo Neri Hospital, ⁴U.O. Gastroenterology, San Camillo Forlanini Hospital, Rome, Italy

Contact E-mail Address: danipug@libero.it

Introduction: Thiopurines have been used for the treatment of inflammatory bowel disease from several years. However there are few evidence-based data to support their efficacy in ulcerative colitis (UC).

Aims & Methods: The aim of our study was to assess the long-term outcome of UC patients receiving thiopurines monotherapy and to identify possible predictors of efficacy in a large cohort of patients.We retrospectively collected data on all UC patients who started monotherapy thiopurines at three tertiary IBD centers from February 1995 to April 2015. Associations between clinical and epidemiological characteristics and treatment efficacy were analyzed with survival regression models clustered for IBD center and adjusted for age, sex and calendar period and expressed as hazard ratios (HRs) and 95% confidence intervals (CIs). Models incorporated treatment failure, intolerance and adverse events as competing risks. Treatment efficacy was defined as either sustained clinical remission on thiopurines treatment or withdrawal of thiopurines for remission.

Results: A total of 234 UC patients started thiopurines during the interval. The mean (SD) age at diagnosis was 39 (15) years and the median duration of disease was 4 years (range 0-32 years). One-hundred and forty-four patients (62%) had pancolitis and 90 (38%) extensive colitis. One-hundred and thirty-two patients (61%) had endoscopic moderate activity and 85 (39%) severe colitis. The main indication for treatment was steroid-dependence for 137 patients (59%). Azathioprine was prescribed to 90% of patients and mercaptopurine to 10%. Participants contributed a total of 760 person-years of follow-up (median follow-up 28 months, range 0.2-207 months). Eighty-eight of 234 patients (38%) maintained clinical remission and were still on thiopurines therapy and 37 of 234 (16%) withdrew thipurines because of sustained remission without clinical relapse. Thiopurines were discontinued in 71 patients (30%) for failure and 35 of these patients (49%) started biologics. Twenty-seven patients (12%) experienced intolerance, in particular: medullary aplasia (n=10, 37%), hepatitis (n=6, 22%), pancreatitis (n=5, 19%), arthromyalgia (n=1, 37%) and other (n=5, 19%). Eleven patients (5%) stopped thiopurines for other reasons. Duration of disease (HR 1.02, 95% CI 0.97, 1.07), disease extension (HR for pancolitis vs extensive colitis 1.01, 95% CI 0.55, 1.85), endoscopic activity at baseline (HR for severe vs moderate colitis 0.83, 95% CI 0.59, 1.18), smoking status (HR for smoking vs non smoking 1.18, 95% CI 0.79, 1.76) and indication for treatment (HR for 5-amynosalicilates refractoriness vs steroid-dependence 1.12, 95% CI 0.72, 1.75 and HR for severe acute attack vs steroid-dependence 1.44, 95% CI 0.98, 2.10) were not significantly associated with treatment effectiveness.

Conclusion: Thiopurines monotherapy was effective in large proportion of UC patients. We could not identify any independent predictors of treatment efficacy in our sample.

Disclosure of Interest: D. Pugliese: None declared, P. M. Ferraro: None declared, A. Aratari: None declared, G. Margagnoni: None declared, R. Monterubbianesi: None declared, C. Felice: None declared, A. Papa: None declared, L. Guidi Lecture fee(s): AbbVie,MSD, Takeda, Zambon, Consultancy: AbbVie,MSD, Mundipharma, A. Kohn: None declared, C. Papi Consultancy: AbbVie,Takeda, MSD, Chiesi, Sofar, A. Armuzzi Financial support for research: MSD, Lecture fee(s): AbbVie, Astra-Zeneca, Chiesi, Ferring, Hospira, MSD, Otsuka, Takeda, Zambon, Consultancy: AbbVie, Hospira, Lilly, MSD, Mundipharma, Pfizer, Sofar, Takeda

P0364 HEALTH-RELATED QUALITY OF LIFE VARIES AS A FUNCTION OF REMISSION STATUS IN PATIENTS WITH MILD-TO-MODERATE ULCERATIVE COLITIS RECEIVING SHORT-TERM AND LONG-TERM DAILY THERAPY WITH MULTIMATRIX MESALAZINE

A. Yarlas¹, G. D'Haens², D. Willshire³, M. Teynor⁴

¹Optum, Lincoln, RI, United States, ²Academic Medical Center, Amsterdam, Netherlands, ³Shire, North Ryde, Australia, ⁴Shire, Lexington, MA, United States

Contact E-mail Address: mteynor@shire.com

Introduction: Studies have shown an inverse relationship between disease activity and health-related quality of life (HRQL) for patients (pts) with ulcerative colitis (UC), such that decreases in disease activity predict better HRQL. Consistent with this are findings that pts with UC in complete (clinical and endoscopic) remission (CR) exhibit better HRQL than pts not in remission (NR). What has not been established is whether HRQL for UC pts in partial remission (PR) is more similar to pts in CR or NR.

Aims & Methods: Data were from a multinational, open-label, prospective trial of multimatrix mesalazine (NCT01124149). During induction treatment, pts with active mild-to-moderate UC received 4.8 g multimatrix mesalazine once daily (QD) for up to 8 weeks. Pts in CR or PR at Week 8 were eligible to receive 12 months of maintenance treatment with 2.4 g multimatrix mesalazine QD. Remission status at Week 8 or early withdrawal (EW) visit during the induction phase (induction endpoint) and at Month 12 or EW visit of the maintenance phase (maintenance endpoint) was determined using a modified UC-Disease Activity Index (UC-DAI). CR was defined as UC-DAI ≤1 with scores of 0 for both rectal bleeding (RB) and stool frequency (SF) components and ≥1-point reduction from baseline for the endoscopy component. PR was defined as UC-DAI ≤3, RB + SF ≤1, and not in complete remission. All EW pts were classified as NR. Pts completed measures of generic HRQL (12-item Short-Form survey [SF-12v2]) and disease-specific HRQL (Shortened Inflammatory Bowel Disease Questionnaire [SIBDQ]) at baseline and at the end of induction and maintenance treatment. Analysis of variance models tested if HRQL scores at both endpoints differed as a function of pts’ remission status. Repeated-measures mixed-effects models (RMMM) tested if changes in HRQL over time varied by maintenance endpoint remission status. All tests used Bonferroni-adjusted P values to control for multiplicity.

Results: The numbers of pts in CR, PR, and NR (including EW pts) were, respectively, 186 (26.6%), 282 (40.3%) and 231 (33.0%) at Week 8, and 159 (39.7%), 103 (25.7%) and 139 (34.7%) at the end of maintenance (Month 12). At both time points, pts in CR and PR scored significantly better on all 8 SF-12v2 and all 4 SIBDQ domains than NR pts (all P <0.0001). Including EW pts in all analyses, there were no statistical differences between scores of CR and PR pts on 7 of 8 SF-12v2 domains (all but bodily pain, P =0.013) or any SIBDQ domains at Week 8, while at Month 12, there were no statistical differences between CR and PR pts on any SF-12v2 or SIBDQ domains (all P ≥0.251). Estimated parameters and means from RMMM indicated that pts in CR or PR showed similarly larger improvements and better maintenance of HRQL over time than did NR pts.

Conclusion: HRQL was similar for pts whose UC was in CR or PR following both short-term and long-term daily treatment with mesalazine. Furthermore, at both endpoints, CR and PR pts exhibited better HRQL than NR pts. These results indicate that improvement and maintenance of HRQL for pts with UC in PR was comparable with those in CR.

Disclosure of Interest: A. Yarlas Financial support for research: Employee of Optum, which received funds from Shire Development LLC to conduct these analyses, Conflict with: Employee of Optum, which received funds from Shire Development LLC to assist in the writing of this abstract, G. D'Haens Financial support for research: Abbvie, Janssen Biologics, Given Imaging, MSD, Dr. Falk Pharma, and Photopill, Lecture fee(s): AbbVie, Tillotts, Tramedico, Ferring, MSD, UCB, Norgine, and Shire, Consultancy: AbbVie, Actogenix, Centocor, Cosmo, enGene, Ferring Pharmaceuticals, GlaxoSmithKline, Janssen Biologics, Millenium Pharmaceuticals, MSD, Novo Nordisk, PDL BioPharma, Pfizer, SetPoint, Shire, Takeda, Teva, and UCB, D. Willshire Shareholder: Shire, Conflict with: Employee of Shire, M. Teynor Shareholder: Shire, Conflict with: Employee of Shire

P0365 REMISSION STATUS PREDICTS WORK-RELATED OUTCOMES FOR PATIENTS WITH MILD-TO-MODERATE ULCERATIVE COLITIS RECEIVING SHORT-TERM AND LONG-TERM DAILY THERAPY WITH MULTIMATRIX MESALAZINE

A. Yarlas¹, G. D'Haens², D. Willshire³, M. Teynor⁴

¹Optum, Lincoln, RI, United States, ²Academic Medical Center, Amsterdam, Netherlands, ³Shire, North Ryde, Australia, ⁴Shire, Lexington, MA, United States

Contact E-mail Address: mteynor@shire.com

Introduction: Studies have shown that increased disease activity for patients with ulcerative colitis (UC) predicts impairment in work-related outcomes (WRO), such as decreased productivity and increased absenteeism. In addition, patients whose UC is in complete (clinical and endoscopic) remission (CR) demonstrate less impairment in WRO than patients whose UC is not in remission (NR). The objective of the current study was to examine WRO of UC patients in partial remission (PR) relative to WRO of patients in CR or NR.

Aims & Methods: Data were from a multinational, open-label, prospective trial of multimatrix mesalazine (NCT01124149). In the induction phase, patients with active mild-to-moderate UC received 4.8 g of multimatrix mesalazine once daily (QD) for 8 weeks. Patients in CR or PR after induction were enrolled in the maintenance phase, during which they received 2.4 g of multimatrix mesalazine QD for 12 months. Remission status at induction endpoint (Week 8 or early withdrawal [EW] visit) and at maintenance endpoint (Month 12 or EW visit) was determined by a patient’s score on a modified UC-Disease Activity Index (UC-DAI). CR was defined as UC-DAI ≤1 with scores of 0 for both rectal bleeding (RB) and stool frequency (SF) components, and ≥1-point reduction from baseline for the endoscopy component. PR was defined as UC-DAI ≤3, RB + SF ≤1, and not in complete remission. Patients who did not complete the full course of treatment were classified as NR.

A UC-specific version of the Work Productivity and Activity Impairment (WPAI:UC) questionnaire measured the impact of UC on 4 WRO domains – absenteeism, presenteeism, overall work impairment (OWI), and activity impairment – at baseline, Week 8, and Month 12 (including EW patients at all time points). Analysis of variance models compared WPAI:UC scores at these time points among CR, PR, and NR patient groups. Changes in OWI scores over time as a function of remission status was examined using a repeated-measures mixed-effects model (RMMM). All tests used Bonferroni-adjusted P values to control for multiplicity.

Results: The numbers of patients in CR, PR, and NR (including EW patients) were, respectively, 186 (26.6%), 282 (40.3%) and 231 (33.0%) at Week 8, and 159 (39.7%), 103 (25.7%) and 139 (34.7%) at Month 12. Patients in CR and PR had significantly lower (better) scores on all WPAI:UC domains than did NR patients at both time points (P <0.05 and P <0.001, respectively). Further, at both induction and maintenance endpoints, WPAI:UC domain scores did not statistically differ between CR and PR patients (all P ≥0.415). Estimated parameters and means from the RMMM indicated that patients in CR or PR showed similarly larger improvements and better maintenance of improvements in OWI over time than did NR patients.

Conclusion: Patients whose UC was in CR or PR following both short-term and long-term daily treatment with multimatrix mesalazine exhibited better WRO than NR patients. Furthermore, WRO was equivalent for patients in CR and PR groups, indicating that improvement and maintenance of WRO for patients who achieved PR was just as good as for those in CR.

Disclosure of Interest: A. Yarlas Financial support for research: Employee of Optum, which received funds from Shire Development LLC to conduct these analyses, Conflict with: Employee of Optum, which received funds from Shire Development LLC to assist in the writing of this abstract, G. D'Haens Financial support for research: Abbvie, Janssen Biologics, Given Imaging, MSD, Dr. Falk Pharma, and Photopill, Lecture fee(s): AbbVie, Tillotts, Tramedico, Ferring, MSD, UCB, Norgine, and Shire, Consultancy: AbbVie, Actogenix, Centocor, Cosmo, enGene, Ferring Pharmaceuticals, GlaxoSmithKline, Janssen Biologics, Millenium Pharmaceuticals, MSD, Novo Nordisk, PDL BioPharma, Pfizer, SetPoint, Shire, Takeda, Teva, and UCB, D. Willshire Shareholder: Shire, Conflict with: Employee of Shire, M. Teynor Shareholder: Shire, Conflict with: Employee of Shire

P0366 MILD TO MODERATELY ACTIVE ULCERATIVE PROCTITIS: ORAL MESALAZINE MMX PLUS RECTAL MESALAZINE VS RECTAL MESALAZINE ALONE

D. Sgambato¹, M. V. D'Auria², A. Miranda¹, C. Cardone³, G. Vicinanza², D. F. Sergio², V. Gallo², M. Romano¹, A. Cuomo²

¹Hepato-Gastroenterology Division, Second University of Naples, Naples, ²UOC Gastroenterologia DEA III Livello, “Umberto I”, Nocera Inferiore, Salerno, ³Oncology Division, Second University of Naples, Naples, Italy

Contact E-mail Address: drcuomo@iol.it

Introduction: Mesalazine (MSZ) 1 g suppository once daily is the preferred initial therapy for the treatment of mild to moderately active ulcerative proctitis (UP). Whether the use of oral mesalazine MMX (MMX) together with rectal MSZ improves the clinical outcome of UP is not known.

Aims & Methods: The aim is to evaluate the efficacy of combination therapy with MSZ suppository plus MMX vs rectal MSZ alone in inducing remission of UP. Secondary endpoint was to assess whether combined therapy had any effect on the extension of the inflammation at 6 months follow-up compared with rectal MSZ alone.

We retrospectively studied 156 consecutive patients (pts) (81males, 75 females) with mild to moderately active UP admitted to our IBD Units, from 2010 to 2014. Forty pts (26%) were excluded from the analysis because they had been treated with oral MSZ other than MMX. Therefore 55 (35%) pts treated with MMX 1200 mg/die plus MSZ suppositories 1g/die and 61 (39%) pts treated with MSZ 1 g suppositories/die alone were included in the study. Patients on combined therapy, stopped daily MSZ suppository after two months and continued MMX 1200 mg/die plus MSZ suppository every other day up to 6 months. Patients treated with MSZ suppository alone, stopped daily rectal MSZ after 2 months and continued with MSZ suppository every other day up to 6 months. After 2 months pts were clinically evaluated according to the partial Mayo score. After 6 months follow-up, pts underwent control endoscopy. Significance of differences was assessed by X₂ test.

Results: After two months follow-up, 46 pts (84%) on combined therapy and 49 pts (80%) on rectal MSZ alone reached clinical remission. At 6 months follow-up, proximal extension of the inflammation both at the endoscopy and histology level was observed in 8/55 (14%) pts on combined therapy and in 18/61(29%) pts on rectal MSZ alone (p < 0.05).

Conclusion: 1) Combined therapy with oral MMX plus rectal MSZ or rectal MSZ alone are equally effective in inducing clinical remission in pts with UP, however, 2) combined oral MMX plus rectal MSZ is associated with a significant reduction in the proximal extension of the disease compared with rectal MSZ alone.

Disclosure of Interest: None declared

P0367 EFFICACY, SAFETY AND LONG-TERM OUTCOME OF ENDOSCOPIC DILATION THERAPY FOR STRICTURING CROHN’S DISEASE - A COMBINED ANALYSIS OF 3252 ENDOSCOPIC BALLOON DILATIONS PROCEDURES

D. Bettenworth¹, R. Lopez², A. Gustavsson³, C. Tysk³, G. van Assche⁴, F. Rieder⁵⁶

¹Medinice B, University Hospital of Münster, Münster, Germany, ²Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, United States, ³Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden, ⁴Division of Gastroenterology, University of Leuven, Leuven, Belgium, ⁵Department of Gastroenterology, Hepatology & Nutrition, Digestive Disease Institute, Cleveland Clinic Foundation, ⁶Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, United States

Contact E-mail Address: dominik.bettenworth@ukmuenster.de

Introduction: Intestinal strictures are a frequent complication of Crohn’s disease (CD), leading to intestinal obstruction. Endoscopic balloon dilation (EBD) represents a widely used approach for the management of intestinal stenosis in CD patients. Available evidence in this area, however, is limited. We therefore performed a combined efficacy and safety analysis based on all studies of endoscopic balloon dilation available in the literature.

Aims & Methods: A systematic literature search regarding EBD in CD was performed. Available technical and clinical variables were extracted from studies with > 15 patients for a descriptive pooled data analysis. Weighted efficacy averages were calculated for sub-groups. Study authors were contacted to provide individual patient data. Frailty models were used with study as a random effect for heterogeneity between studies. An automated stepwise variable selection method was used to choose variables in the multivariable models. In addition, generalized linear mixed models were used to assess associations. Binomial distribution with log link was used for all the other outcomes.

Results: 34 studies with a total of 1500 CD patients and 3252 performed dilation procedures were included. 82.7% of intestinal strictures were located in the ileum and 66.4% were anastomotic strictures (33.6% de novo, respectively). Technical success rate was 89.9% of all patients, resulting in clinical efficacy in 79.5% of patients. Major complications, defined as perforation, bleeding or dilation-related surgery, occurred in 2.6% of all procedures. During a mean follow-up period of 39.8 months, 48.6% of patients reported symptomatic recurrence, while 30.2% of all patients had to undergo surgical intervention. Concomitant therapy with steroid injection and cutting techniques post dilation was associated with a poorer dilation efficacy (all p < 0.001).

Multivariate analysis of 676 individual patients from 12 studies identified a 50% higher hazard of re-dilation in CD with de novo strictures as compared to anastomotic strictures (p=0.014). Additionally, concomitant therapy with steroid injection doubled the hazard of need for re-dilation (p=0.029). A greater maximum dilation diameter (per 1 mm increase) was found to be associated with a higher likelihood of both, technical success (p=0.004) and scope passing (p=0.001). Finally, every 1 cm increase of stricture length increased the hazard of need for surgery by 8% (p=0.008).

Conclusion: EBD has a high rate of short-term technical and clinical success with substantial long-term efficacy and acceptable complication rates. Main predictors of successful EBD are a greater maximum caliber of dilation and anastomotic stricture. Steroid injection and an increased length of stricture reduced time to surgical intervention. EBD is a valuable alternative to surgery in patients with CD associated strictures.

Disclosure of Interest: None declared

P0368 IN VITRO AND IN VIVO PROPERTIES OF NR11/1943, A NEW CCR9 RECEPTOR ANTAGONIST

S. B. Kalindjian¹, S. V. Kadnur², R. Fairclough¹, C. A. Hewson¹, S. Juluri², Z. Mohamed², R. Saxena³, J. Aiyar², D. McVey¹

¹Norgine Limited, Uxbridge, United Kingdom, ²Jubilant Biosys, Bangalore, ³Jubilant Chemsys Limited, Noida, India

Contact E-mail Address: dmcvey@norgine.com

Introduction: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder in which tissue damage and inflammation lead to long-term, often irreversible, impairment of the structure and function of the gastrointestinal tract. Chemokine Receptor 9 (CCR9) is expressed on lymphocytes in the circulation, and is the key chemokine receptor that enables these cells to home to the small intestine due to the localised expression of its ligand, Chemokine (C-C) Ligand 25 (CCL25). It has been suggested that CCR9 antagonism represents a means to prevent the aberrant immune response in IBD. NR11/1943 has been identified as a promising, small-molecule candidate by a medicinal chemistry programme, aimed at producing an orally-available CCR9 antagonist with a superior pharmacokinetic (PK) profile to vercirnon, a first generation compound of this class.

Aims & Methods: In this study we describe the in vitro and in vivo properties of a new, orally-available CCR9 antagonist molecule using various calcium-flux and chemotaxis based assays and in vivo procedures and models commonly used in the early discovery and development phases of new IBD therapies.

Results: In a number of experiments, studying the interaction between the CCR9 receptor and NR11/1943, inhibitory constants (Ki) were obtained ranging from 6nM to 24nM showing the compound to be a potent antagonist of the receptor. PK data demonstrated that the molecule has an excellent profile, being highly bio-available and with a long half-life in all the species studied. Following BID oral dosing, the molecule also demonstrated efficacy in three different models of colitis in mice (3 mg/kg to 100mg/kg) and rats (30 mg/kg and 120 mg/kg), showing significant protection against DSS- and TNBS-induced weight loss and other adverse effects, especially with respect to faecal consistency and intestinal bleeding.

Conclusion: NR11/1943 is an orally available CCR9 antagonist with a superior pre-clinical PK profile to vercirnon and with suitable pharmacological properties, both in vitro and in vivo, to allow it to progress towards the clinic.

Disclosure of Interest: S. B. Kalindjian Conflict with: Employee of Norgine, S. Kadnur Conflict with: Contractor to Norgine, R. Fairclough Conflict with: Employee of Norgine, C. Hewson Conflict with: Employee of Norgine, S. Juluri Conflict with: Contractor to Norgine, Z. Mohamed Conflict with: Contractor to Norgine, R. Saxena Conflict with: Contractor to Norgine, J. Aiyar Conflict with: Contractor to Norgine, D. McVey Conflict with: Employee of Norgine

P0369 CROSS-SPECIES TRANSLATABILITY OF NONCLINICAL SAFETY ASSESSMENTS OF A HUMAN INTERLEUKIN-22FC, AN IG FUSION PROTEIN FOR THE POTENTIAL TREATMENT OF INFECTIOUS OR INFLAMMATORY DISEASES

D. W. Lee¹, S. Zhong², R. Pai³, E. Doudement⁴, E. Stefanich², J. Rae², J. Gutierrez², J. Lutman², X. Wang², A. Lekkerkerker², J. Qiu², K. Loyet², A. Herman², W. Ouyang², M. Keir², D. Danilenko²

¹Safety Assessment, ²Genentech, South San Franciso, ³Medivation, San Francisco, United States, ⁴HEC Business School, Paris, France

Contact E-mail Address: lee.donnaw@gene.com

Introduction: Interleukin 22 (IL22) belongs to the IL10 cytokine family (Ouyang et al. 2011) and binds specifically to the IL22 receptor (IL-22R) heterodimer, expressed on a variety of epithelial tissues (Gurney 2004). Due to its ability to modulate innate immunity via activation of the transcription factor, STAT3, and subsequent regenerative and protective properties (Wolk et al. 2004), IL-22 is thought to have therapeutic potential in treating tissue injury or chronic tissue damage.

Aims & Methods: To assess the pharmacological activity of IL-22 recombinant fusion protein (IL-22Fc) that links the human cytokine IL-22 with the Fc portion of a human immunoglobulin, STAT3 activation was evaluated in primary hepatocytes isolated from human, cynomolgus monkey, minipig, rat, and mouse after incubation with IL-22Fc. The nonclinical safety profile of IL-22Fc was evaluated to establish a safe clinical starting dose for humans in Phase I trials and support clinical intravenous (IV) and/or subcutaneous (SC) treatment regimen. Studies included pilot systemic toxicity studies in mice, rats, and cynomolgus monkeys; and repeat-dose GLP systemic toxicity studies, one in rats and one in cynomolgus monkeys. In addition, a pilot single-dose SC local toxicity study was performed in minipigs; and a tissue cross-reactivity study was conducted ex vivo using human and cynomolgus monkey tissues.

Results: Results demonstrated that all species achieved similar levels of STAT3 phosphorylation but higher concentrations of IL-22Fc and longer incubation times were required to achieve equivalent levels of STAT3 phosphorylation in rat hepatocytes when compared to hepatocytes from other species. Taken together, these results confirmed that the cynomolgus monkey, minipig, rat, and mouse were all appropriate nonclinical species for toxicology studies, and that the rat was not as sensitive to the effects of IL-22Fc as the cynomolgus monkey. Systemically administered IL-22Fc was well tolerated in both cynomolgus monkeys and rats up to highest doses tested. In monkeys, skin reddening with microscopic findings of dose-dependent epidermal hyperplasia or acanthosis, sometimes accompanied by variable increased vascularity in the superficial dermis was observed. In addition, cynomolgus monkeys exhibited transient and dose-dependent increases in acute phase reactants (Sonnenberg et al. 2011), without a concomitant increase in any proinflammatory cytokines or chemokines. Epidermal hyperplasia was also observed in mice, rats and minipigs.

Conclusion: Results from these nonclinical studies demonstrate the cross-species translatability of the biological response in activating the IL-22 pathway as well as the translatability of findings from in vitro to in vivo systems. The predicted safety risks for IL-22Fc are exaggerated pharmacologic effects of epidermal hyperplasia and a transient increase in acute phase proteins, both of which are considered predictable, manageable, monitorable, and reversible in the clinic.

Disclosure of Interest: D. Lee Shareholder: Roche, S. Zhong Shareholder: Roche, R. Pai Shareholder: Medivation, E. Doudement: None declared, E. Stefanich Shareholder: Roche, J. Rae Shareholder: Roche, J. Gutierrez Shareholder: Roche, J. Lutman Shareholder: Roche, X. Wang: None declared, A. Lekkerkerker Shareholder: Roche, J. Qiu Shareholder: Roche, K. Loyet Shareholder: Roche, A. Herman Shareholder: Roche, W. Ouyang Shareholder: Roche, M. Keir Shareholder: Roche, D. Danilenko Shareholder: Roche

P0370 FIRST OBSERVATIONS OF THE USE OF BIOSIMILAR INFLIXIMAB FOR TREATMENT OF ULCERATIVE COLITIS AND CROHN DISEASE IN PAEDIATRIC POPULATION

D. Jarzębicka¹, J. Sieczkowska¹, M. Dądalski¹, J. Kierkuś¹

¹Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children’s Memorial Health Institute, Warsaw, Poland

Contact E-mail Address: dorota.jarzebicka@wp.pl

Introduction: Biosimilar infliximab (Remisma/Inflectra) was introduced into therapy in European Union and also in Poland at the beginning of 2014. Biosimilar infliximab (BI) was authorised based on preclinical and clinical studies and is considered therapeutically equivalent in terms of safety and efficacy to the reference infliximab.

Aims & Methods: The aim of the study was to present first, to our knowledge, observation on the safety and efficacy of BI in children with ulcerative colitis and Crohn disease. From the beginning of 2014 we start treatment with biosimilar infliximab Remsima (5mg/kg) patient with ulcerative colitis (9 patients) and Crohn disease (16 patients). Patients received BI at weeks 0, 2 and 6. Disease activity (PUCAI/PCDAI) and laboratory values (CRP, ESR, platelet count) were assessed at qualification for the biological treatment and after induction treatment at week 10. Mean and range of clinical values is reported.

Results: Median age of 9 patients with UC was 15 years (range 4.5-17.5). Mean PUCAI before infliximab initiation was 48 (range 5-85). Mean (range) CRP, ESR and platelet count before initiation were 1.95 mg/dL (0.03-8.05), 31 mm (25-38) and 451x10⁹/L (259-786x10⁹). For 2 patients it was the second course of biological treatment. For 2 from 9 patients treatment was discontinued, in 1 due to lack of response after first dose (disease flare), in second due to allergy reaction during dose 3 infusion. As of April 2014, 6 patients received 3 doses and were evaluated at week 10. After 3 doses of biosimilar infliximab mean PUCAI values decreased to 30 (range 0-65). CRP, ESR and platelet count were 0.6 mg/dL (0.02-1.77), 29 mm (18-65) and 510x10⁹ (236-706), respectively. In the group of patients with Crohn disease (16 patients) median age was 17.7 years (range 3-18). At BI start mean PCDAI was 45 (range 15-65); CRP, ESR, platelet count values were 2.05 mg/dL (0.14-6.92), 30 mm (3-93), 362x10⁹/L (235-573x10⁹), respectively. Eight out of 16 patients were previously treated with a biologics (7 with reference infliximab, 1 with adalimumab). Time of previous treatment was mean 20 months (6-59) with biologic-free interval of 23 months (10-72). Actual treatment was discontinued in 2 from 16 patients, after first BI dose due to lack of response, accompanied by adverse event in one patient and withdrawal of consent in second patient. As of April 2014, 10 out of 14 patients received all 3 induction doses. For those patients, median initial PCDAI was 47 (15-62.5) and decreased to 6.75 (0-27.5) . Before treatment and at week 10 CRP, ESR and platelet count were 2.8 (0.15-6.92), 35.4 (3-93), 375x10⁹ (235-573) and 0.53 (0.03-2.62), 18 (6-52), 285x10⁹ (228-340), respectively. Adverse events during infusion were observed in 2/16 patients: one allergic reaction leading to treatment discontinuation and one blood pressure rise that resolved after infusion rate lowering.

Conclusion: In this preliminary report BI appears to be safe and efficacious in inducing remission in ulcerative colitis and Crohn disease paediatric patients. No unexpected safety and product quality issues were identified. Further studies with larger patient groups are required.

Disclosure of Interest: None declared

P0371 CORTICOSTEROID DOSE REDUCTION WITH VEDOLIZUMAB TREATMENT OF CROHN’S DISEASE

E. V. Loftus Jr¹, C. A. Siegel², R. Panaccione³, W. J. Sandborn⁴, M. Smyth⁵, A. Green⁵, J. Xu⁶, B. Abhyankar⁵

¹Mayo Clinic, Rochester, ²Dartmouth-Hitchcock Medical Center, Hanover, United States, ³University of Calgary, Calgary, Canada, ⁴University of California San Diego, La Jolla, United States, ⁵Takeda Development Centre Europe Ltd, London, United Kingdom, ⁶Takeda Pharmaceuticals International Co, Cambridge, United States

Introduction: Corticosteroids (CS) can effectively induce remission of Crohn’s disease (CD), but serious side effects prohibit long-term use. Vedolizumab (VDZ) maintenance therapy resulted in a greater percentage of patients (pts) with CS-free remission at week (wk) 52 versus placebo (PBO) in the phase 3 GEMINI 2 study of moderately to severely active CD.¹

Aims & Methods: In GEMINI 2, pts who responded to VDZ induction therapy at wk 6 were re-randomised to PBO or VDZ for 46 wks. From wk 6 onward, pts with clinical response discontinued CS use. With exploratory and post hoc analyses, we characterised CS dose reductions following VDZ therapy in pts on stable CS doses (≤30 mg/day prednisone or equivalent) at wk 0. Median CS dose over time, change from baseline CS dose, and CS-free status at wk 52 were summarised overall and by anti-tumour necrosis factor (anti-TNF) treatment (naïve or failure) history. Median-based analyses were used since the data were not normally distributed.

Results: At wk 52, numerically similar percentages of VDZ- and PBO-treated pts had reductions from baseline CS dose (Table). The median CS dose in either treatment group (VDZ or PBO) at wk 52 was 5 mg/day. Higher percentages of pts (overall and anti-TNF-naïve) had doses ≤7.5 mg/day with VDZ versus PBO (Table). In anti-TNF-naïve pts, the median CS dose at wk 52 was 2.7 mg/day with VDZ (vs 5.0 mg/day with PBO). Higher percentages of VDZ-treated pts were CS-free for 90 and 180 days at wk 52 than PBO-treated pts (Table).

Conclusion: VDZ therapy was associated with a numerically higher percentage of CS-free pts and a longer duration of being CS-free than PBO. Interpretation of these post hoc analyses, including the degree of dose reduction, is limited by CS discontinuation on study and small sample sizes.

Abstract number: P0371 Table.

CS Dose Reductions at Wk 52

Wk 52	Anti-TNF-Naïve		Anti-TNF-Failure		Overall
	PBOn=29b	VDZan=55b	PBOn=33b	VDZan=68b	PBOn=65b	VDZan=127b
No. of Pts (%)
No change in CS dose	6 (21)	8 (15)	7 (21)	20 (29)	14 (22)	28 (22)
CS dose increased	5 (17)	3 (5)	6 (18)	10 (15)	11 (17)	13 (10)
CS dose decreased	18 (62)	44 (80)	20 (61)	38 (56)	40 (62)	86 (68)
By <25%	2 (7)	5 (9)	2 (6)	1 (1)	5 (8)	6 (5)
By 25 to <50%	2 (7)	1 (2)	2 (6)	5 (7)	4 (6)	6 (5)
By 50 to <75%	2 (7)	5 (9)	4 (12)	4 (6)	6 (9)	9 (7)
By 75 to <100%	4 (14)	8 (15)	9 (27)	13 (19)	13 (20)	21 (17)
By 100% (CS-free)	8 (28)	25 (45)	3 (9)	15 (22)	12 (18)	44 (35)
CS-free for 90 daysc	16 (40)	36 (49)	5 (13)	18 (21)	23 (28)	57 (35)
CS-free for 180 daysc	12 (30)	34 (46)	4 (11)	17 (20)	18 (22)	53 (33)
Daily CS dose ≤7.5 mg	13 (45)	36 (66)	14 (42)	30 (44)	28 (43)	70 (55)

^aVDZ every 4 or 8 wks.

^bPts on CS according to the interactive voice response system (IVRS) at screening and also on steroids for CD at baseline (wk 0).

^cPts on CS according to the IVRS at screening; anti-TNF-naïve: PBO n=40, VDZ n=74; anti-TNF-failure: PBO n=38, VDZ n=84; overall: PBO n=82, VDZ n=162.

Disclosure of Interest: E. Loftus Jr Financial support for research: AbbVie, UCB, Bristol-Myers Squibb, Shire, Takeda, Amgen, Pfizer, Genentech, Janssen, GlaxoSmithKline, Robarts Clinical Trials, Consultancy: AbbVie, UCB, Takeda, Janssen, MedImmune, Celgene, Immune Pharmaceuticals, Theradiag, Progentec Biosciences, C. Siegel Financial support for research: Salix Pharmaceuticals, Inc., Abbvie, JanssenCilag, UCB, Inc., Lecture fee(s): Abbvie, Janssen-Cilag, Consultancy: Abbvie, UCB, Inc., Lilly, Janssen-Cilag, Given Imaging, Prometheus Laboratories Inc., Takeda, Pfizer, Amgen, Shareholder: Colonary Concepts, Conflict with: Colonary Concepts, R. Panaccione Financial support for research: Abbott, Osiris Therapeutics, Inc., UCB, Inc., Lecture fee(s): Abbott, Centocor, Inc., Medscape, Elan Pharmaceuticals, Inc., Consultancy: Abbott, Biogen/IDEC, Axcan Pharma Inc., Bristol-Myers Squibb, Centocor, Inc., Chemocentryx, Ferring Pharmaceuticals Inc, Lippincott Williams & Wilkins, PDL BioPharma, Inc., Novartis Pharmaceuticals, Genentech Inc., Elan Pharmaceuticals, Inc., UCB, Inc., W. Sandborn Financial support for research: Bristol-Myers Squibb, Consultancy: ActoGeniX NV, Amgen, AM-Pharma BV, Boehringer Ingelheim Inc, Bristol Meyers Squibb, Celgene, Cosmo Technologies, Coronado Biosciences, Eisai Medical Research Inc., Elan Pharmaceuticals, Eli Lilly, Ferring Pharmaceuticals, Genentech, Gilead Sciences, Glaxo Smith Kline, Ironwood Pharmaceuticals, Janssen, Lexicon Pharmaceuticals, Millennium Pharmaceuticals, Nisshin Kyorin Pharmaceuticals Co., Ltd, Novo Nordisk A/S, Orexigen Therapeutics, Inc., Pfizer, Prometheus Laboratories, Receptos, Bristol-Myers Squibb, M. Smyth Conflict with: Employee of Takeda Development Centre Europe Ltd, London, UK, A. Green Conflict with: Employee of Takeda Development Centre Europe Ltd, London, UK, J. Xu Conflict with: Employee of Takeda Pharmaceuticals International Co, Cambridge, Massachusetts, USA, B. Abhyankar Conflict with: Employee of Takeda Development Centre Europe Ltd, London, UK

P0372 CORTICOSTEROID DOSE REDUCTION IN ULCERATIVE COLITIS PATIENTS TREATED WITH VEDOLIZUMAB

E. V. Loftus Jr¹, C. A. Siegel², R. Panaccione³, W. J. Sandborn⁴, M. Smyth⁵, A. Green⁵, J. Xu⁶, B. Abhyankar⁵

¹Mayo Clinic, Rochester, ²Dartmouth-Hitchcock Medical Center, Hanover, United States, ³University of Calgary, Calgary, Canada, ⁴University of California San Diego, La Jolla, United States, ⁵Takeda Development Centre Europe Ltd, London, United Kingdom, ⁶Takeda Pharmaceuticals International Co, Cambridge, United States

Introduction: Corticosteroids (CS) are effective for the short-term treatment of patients (pts) with ulcerative colitis (UC), but serious side effects prohibit long-term use. In the GEMINI 1 study, a higher percentage of pts with moderately to severely active UC were in CS-free remission at week (wk) 52 with vedolizumab (VDZ) treatment than with placebo (PBO).¹

Aims & Methods: In GEMINI 1, pts who responded to VDZ induction therapy at wk 6 were re-randomised to PBO or VDZ for 46 wks. From wk 6 onward, pts with clinical response discontinued CS use. We characterised CS dose reductions achieved with VDZ therapy in exploratory and post hoc analyses of pts with baseline (wk 0) CS use (≤30 mg/day prednisone or equivalent). Median CS dose over time, change from baseline CS dose, and CS-free status at wk 52 were summarised overall and by anti-tumour necrosis factor (anti-TNF) treatment (naïve or failure) history.

Results: Of pts with baseline CS use, 74% decreased their CS dose with VDZ treatment (vs 57% with PBO) (Table). At wk 52, 56% of VDZ-treated pts were on ≤7.5 mg/day of CS (Table), and the median CS dose was 2.5 mg/day for VDZ-treated pts and 10.0 mg/day for PBO. Numerically higher percentages of VDZ-treated pts were CS-free for 90 and 180 days at wk 52 than PBO-treated pts (Table). Similar trends were observed in the anti-TNF-naïve and anti-TNF-failure populations.

Abstract number: P0372 Table.

CS Dose Reductions at Wk 52.

Wk 52	Anti-TNF-Naïve		Anti-TNF-Failure		Overall
	PBOn=40b	VDZan=82b	PBOn=21b	VDZan=42b	PBOn=67b	VDZan=140b
No. of Pts (%)
No change in CS dosec	8 (20)	13 (16)	4 (19)	5 (12)	14 (21)	21 (15)
CS dose increasedc	8 (20)	4 (5)	5 (24)	2 (5)	14 (21)	10 (7)
CS dose decreasedc	24 (60)	63 (77)	12 (57)	33 (79)	38 (57)	104 (74)
By <25%	1 (3)	2 (2)	2 (10)	2 (5)	4 (6)	4 (3)
By 25 to <50%	4 (10)	5 (6)	0 (0)	4 (10)	4 (6)	12 (9)
By 50 to <75%	9 (23)	8 (10)	2 (10)	6 (14)	11 (16)	15 (11)
By 75 to <100%	0 (0)	11 (13)	5 (24)	9 (21)	6 (9)	19 (14)
By 100% (CS-free)	10 (25)	37 (45)	3 (14)	12 (29)	13 (19)	54 (39)
CS-free for 90 daysd	13 (30)	52 (63)	3 (13)	16 (36)	17 (24)	73 (51)
CS-free for 180 daysd	12 (28)	50 (60)	2 (9)	14 (31)	15 (21)	69 (48)
Daily CS dose ≤7.5 mgd	13 (30)	52 (63)	9 (39)	23 (51)	23 (32)	80 (56)

^aVDZ every 4 or 8 wks.

^bPts on CS according to the interactive voice response system (IVRS) at screening and also on steroids for UC at baseline (wk 0).

^cPts with missing data; anti-TNF-naïve: VDZ n=2 (2%); anti-TNF-failure: VDZ n=2 (5%); overall: PBO n=1 (1%), VDZ n=5 (4%).

^dPts on CS according to the IVRS at screening; anti-TNF-naïve: PBO n=43, VDZ n=83; anti-TNF-failure: PBO n=23, VDZ n=45; overall: PBO n=72, VDZ n=143.

Conclusion: At wk 52, numerically greater reductions in CS use were achieved with VDZ compared with PBO. VDZ therapy was associated with a numerically higher percentage of CS-free pts and a longer duration of being CS-free than PBO. Interpretation of these post hoc analyses, including the degree of dose reduction, is limited by CS discontinuation on study and small sample sizes.

The clinical study was funded by Millennium Pharmaceuticals, Inc (d/b/a Takeda Pharmaceuticals International Co). Medical writing assistance was provided by inVentiv Medical Communications and supported by Takeda Pharmaceuticals International, Inc.

Disclosure of Interest: E. Loftus Jr Financial support for research: AbbVie, UCB, Bristol-Myers Squibb, Shire, Takeda, Amgen, Pfizer, Genentech, Janssen, GlaxoSmithKline, Robarts Clinical Trials, Consultancy: AbbVie, UCB, Takeda, Janssen, MedImmune, Celgene, Immune Pharmaceuticals, Theradiag, Progentec Biosciences, C. Siegel Financial support for research: Salix Pharmaceuticals, Inc., Abbvie, JanssenCilag, UCB, Inc., Lecture fee(s): Abbvie, Janssen-Cilag, Consultancy: Abbvie, UCB, Inc., Lilly, Janssen-Cilag, Given Imaging, Prometheus Laboratories Inc., Takeda, Pfizer, Amgen, Shareholder: Colonary Concepts, Conflict with: Colonary Concepts, R. Panaccione Financial support for research: Abbott, Osiris Therapeutics, Inc., UCB, Inc., Lecture fee(s): Abbott, Centocor, Inc., Medscape, Elan Pharmaceuticals, Inc., Consultancy: Abbott, Biogen/IDEC, Axcan Pharma Inc., Bristol-Myers Squibb, Centocor, Inc., Chemocentryx, Ferring Pharmaceuticals Inc, Lippincott Williams & Wilkins, PDL BioPharma, Inc., Novartis Pharmaceuticals, Genentech Inc., Elan Pharmaceuticals, Inc., UCB, Inc., W. Sandborn Financial support for research: Bristol-Myers Squibb, Consultancy: ActoGeniX NV, Amgen, AM-Pharma BV, Boehringer Ingelheim Inc, Bristol Meyers Squibb, Celgene, Cosmo Technologies, Coronado Biosciences, Eisai Medical Research Inc., Elan Pharmaceuticals, Eli Lilly, Ferring Pharmaceuticals, Genentech, Gilead Sciences, Glaxo Smith Kline, Ironwood Pharmaceuticals, Janssen, Lexicon Pharmaceuticals, Millennium Pharmaceuticals, Nisshin Kyorin Pharmaceuticals Co., Ltd, Novo Nordisk A/S, Orexigen Therapeutics, Inc., Pfizer, Prometheus Laboratories, Receptos, Bristol-Myers Squibb, M. Smyth Conflict with: Employee of Takeda Development Centre Europe Ltd, London, UK, A. Green Conflict with: Employee of Takeda Development Centre Europe Ltd, London, UK, J. Xu Conflict with: Employee of Takeda Pharmaceuticals International Co, Cambridge, Massachusetts, USA, B. Abhyankar Conflict with: Employee of Takeda Development Centre Europe Ltd, London, UK

P0373 PROGNOSIS OF PATIENTS WITH ULCERATIVE COLITIS IN SUSTAINED REMISSION AFTER THIOPURINES WITHDRAWAL

E. Moreno Rincón¹, J. M. Benítez¹, F. J. Serrano Ruiz¹, J. M. Vázquez Morón², H. Pallarés Manrique², J. M. Herrera Justiniano³, E. Leo Carnerero³, M. R. Gómez García⁴, M. J. Cabello Tapia⁴, M. Castro Fernández⁵, M. Rojas Feria⁵, L. Castro Laria⁶, F. Argüelles Arias⁶, R. Carmargo Camero⁷, G. Alcaín Martínez⁷, E. Iglesias Flores¹, V. García Sánchez¹, on behalf of Grupo Andaluz de Enfermedad Inflamatoria Intestinal

¹Gastroenterology, University Hospital Reina Sofía, Córdoba, ²Gastroenterology, University Hospital Juan Ramón Jiménez, Huelva, ³Gastroenterology, University Hospital Virgen del Rocío, Sevilla, ⁴Gastroenterology, University Hospital Virgen de las Nieves, Granada, ⁵Gastroenterology, University Hospital Nuestra Señora de Valme, ⁶Gastroenterology, University Hospital Virgen Macarena, Sevilla, ⁷Gastroenterology, University Hospital Virgen de la Victoria, Málaga, Spain

Contact E-mail Address: estefania.mr.86@gmail.com

Introduction: The ideal length of treatment with thiopurines in ulcerative colitis (UC) patients in sustained remission remains unknown. It is widely accepted that the withdrawal of these drugs is associated with a worse outcome of the disease.

Aims & Methods: The aim of this study is to analyze the clinical outcome after this withdrawal and to identify possible predictors of clinically significant relapse (CSR).

A multicenter, observational and retrospective study was designed. 102 patients with UC who discontinued thiopurines in a situation of sustained free-steroid clinical remission were included. All the patients were followed up until last revision or until CSR (understood as the occurrence of signs and symptoms of UC that required a rescue treatment).

Results: The mean duration of the disease in all patients was 13 +/- 0.61 years, the median time from diagnosis to the start of thiopurines was 48.14 +/- 5.51 months and the mean duration of total treatment with thiopurines was 60.87 +/- 4.89 months. After thiopurines withdrawal, overall CSR was recorded in 32.35% of the patients. The cumulative percentage was 18.88% in the first year, 36.48% in the third year and 43.04% in the fifth year after withdrawal. On multivariate analysis, predictors of relapse were the time from diagnosis of UC until the starting of thiopurines (HR 1.01; 95% CI, 1.01-1.02; p=0.039), the duration of treatment with thiopurines (HR 0.15; 95% CI, 0.03-0.66; p=0.013), the situation of biological remission at withdrawal (HR 0.004; 95% CI, 0.0001-0.14; p=0.0021), the number of relapses before the withdrawal (HR 1.3; 95% CI, 1.01-1.66; p=0.029) and pancolitis (HR 5.01; 95% CI, 1.95-26.43; p=0.0277).

Conclusion: The withdrawal of thiopurines in patients with UC, although in sustained remission, is related to a high relapse rate. Clinical variables such as the extent of the disease, the total duration of treatment or time from diagnosis to the start of thiopurines should be considered before stopping these drugs. Further controlled, randomized and prospective studies with long follow-up periods are required to clarify this issue.

Disclosure of Interest: None declared

P0374 CUMULATIVE INCIDENCE OF, RISK FACTORS FOR AND OUTCOME OF DERMATOLOGICAL COMPLICATIONS OF ANTI-TNF THERAPY IN INFLAMMATORY BOWEL DISEASE: A 14-YEAR EXPERIENCE

E. Fréling¹², C. Baumann³, J.-F. Cuny¹², M.-A. Bigard²⁴, J.-L. Schmutz¹², A. Barbaud¹², L. Peyrin-Biroulet²⁴

¹Dermatology and Allergy Department, Nancy University Hospital, ²Lorraine University, ³Unité ESPRI, ⁴Hepato-Gastroenterology Department, Nancy University Hospital, Vandoeuvre-Les-Nancy, France

Contact E-mail Address: peyrinbiroulet@gmail.com

Introduction: The broader and prolonged use of anti-tumor necrosis factor (TNF) agents in inflammatory bowel disease (IBD) could expose patients to an increased risk of adverse reactions, including dermatological complications.

Aims & Methods: We assessed the cumulative incidence of anti-TNF-induced cutaneous adverse reactions in IBD patients, their risk factors, their dermatological management and their outcome in a large cohort of IBD patients.

In a single-center observational retrospective study including all consecutive adult IBD patients treated with anti-TNF agent between 2001 and 2014, all patients with dermatological complications under anti-TNF therapy were identified in a well-defined cohort of IBD patients. We conducted a survival analysis to determine the cumulative incidence of dermatological complications and risk factors for developing any dermatological complications, cutaneous infections and psoriasiform lesions. Survival curves were estimated by the Kaplan-Meier method, and we used a Cox proportional hazards model to test the association between parameters and time to each event: any dermatological complication, cutaneous infections, and psoriasis lesions.

Results: Among 583 IBD patients, 176 dermatological complications occurred, involving 20.5% of patients. Median duration of follow-up was 38.2 months (Range: 1-179). Psoriasiform lesions (10.1%; 59/583) and cutaneous infections (11.6%, 68/583) were the most frequently observed, with a cumulative incidence of respectively 28.9% and 17.6% at 10 years. They led to anti-TNF discontinuation respectively in 18.6% and 2.9% of patients. In case of switching to another anti-TNF agent for psoriasiform lesions, recurrence occurred in 57% of patients. Ulcerative colitis was associated with a lower risk of developing cutaneous infections than Crohn’s disease (HR 0.25; 95% CI, 0.09-0.68; p=0.007). Higher dosing of infliximab, longer duration of treatment, and maintenance regimen were associated with a higher risk of developing cutaneous infections (respectively p=0.01, p < 0.001, and p=0.04). A younger age at time of anti-TNF initiation was associated with a risk of psoriasiform lesions (HR 5.11; 95% CI, 2.43-11.16; p < 0.001).

Conclusion: Dermatological complications involve one of 5 patients treated with anti-TNF therapy after a 14-year follow-up. Association of cutaneous infections with higher infliximab dosing, shorter intervals between infliximab infusions, and maintenance regimen suggests a dose-dependent effect. Discontinuation of anti-TNF therapy due to dermatological complications is required in one out of 5 patients with psoriasiform lesions, but specific dermatological treatment allows to continue anti-TNF therapy in half of them.

Disclosure of Interest: E. Fréling: None declared, C. Baumann: None declared, J.-F. Cuny: None declared, M.-A. Bigard Lecture fee(s): Abbvie, MSD, Sanofi Aventis, Consultancy: Abbvie, MSD, Sanofi Aventis, J.-L. Schmutz Lecture fee(s): Amgen, Pfizer, Abbvie, Janssen, Consultancy: Amgen, Pfizer, Abbvie, Janssen, A. Barbaud: None declared, L. Peyrin-Biroulet Lecture fee(s): MSD, Abbvie, Biogaran, Hospira, Consultancy: MSD, Abbvie, Biogaran, Hospira

P0375 AN EVALUATION OF A PHARMACIST-LED TELEPHONE CLINIC WITH REGARD TO MONITORING, SAFETY AND QUALITY OF SERVICE ON PATIENTS TAKING THIOPURINES FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASE (IBD) AND AUTOIMMUNE HEPATITIS (AIH) AT BARNSLEY HOSPITAL NHS

F. Fuertes¹, V. Sathyanarayana², K. Kapur², A. Soliman², K. Muhdi², E. Said², D. West², N. Sanassee¹, G. Smith¹, D. Bullas², M. V. Smith¹

¹Pharmacy, ²Gastroenterology, Barnsley Hospital NHS Foundation Trust, Barnsley, United Kingdom

Contact E-mail Address: fernandogarciafuertes@nhs.net

Introduction: Monitoring of patients on immunomodulators increases the workload of consultants in gastroenterology outpatient clinics. This study evaluates how a clinical pharmacist can improve drug monitoring outcomes, safety and quality of service for patients taking thiopurines for IBD and AIH^1,2

Aims & Methods: The number of patients seen at the pharmacist-led IBD clinic for the research period of three months was 81. Patients were seen initially once face to face then follow-up by telephone consultation. Three different quantitative forms were designed and validated for the evaluation of the study. The first one evaluated the quality of the service, the second evaluated each blood test requested in clinic and the third evaluated the overall patient’s clinical performance for the research period. The satisfaction questionnaires were posted to them, advising them to return it anonymously.

Results: The number of patients in the study were 81 [(45 Female); median age 46 years; range age [18-74]]. Indications were IBD (n= 75), AIH (n=6). The questionnaires were posted to each patient (n=81), 51.8% (n=42) were returned anonymously with responses. A vast majority found the telephone follow up clinic to be conventient 92.9% (n=39) and 95.2% (n=48) were satisfied with the clinic service.

The therapeutic target was not achieved in 39.5% (n=32) of the patients due to drug intolerance. Consequently, 29.6% (n=24) of the patients needed a check of the level of thioguanine nucleotides (TGN) for better dose adjustment.³ The results showed sub-therapeutic TGN levels in 13.6% (n=11), a high TGN level in 14.8% (n=12) and 1.2% (n=1) shows non-adherence to therapy.

The total number of blood tests monitored were 304; 85.5% (n=260) were scheduled as expected, 12.8% (n=39) were rescheduled by the pharmacist and 1.6% (n=2) did not attend so therapy was discontinued. The number of blood tests identified in clinic with white cell counts and neutrophils below lower limit is 6.9% (n=21) but only 2.5% (n=2) of the blood tests led the pharmacist to stop therapy and refer back to gastroenterologist.

Conclusion: In conclusion, the pharmacist-led clinic is a safe alternative to traditional clinical monitoring of patients initiated on immunomodulators. It reduces the number of patients who had to discontinue treatment due to myelosuppression, optimises dosage by TGN level, and increases adherence to blood monitoring. It reduces the number of doctor visits due to monitoring and thereby proves to be a cost-effective strategy.

Disclosure of Interest: None declared

P0376 AN OPEN-LABEL, PILOT STUDY TO ASSESS FEASIBILITY AND SAFETY OF FECAL MICROBIOTA TRANSPLANTATION IN PATIENTS WITH MILD-MODERATE ULCERATIVE COLITIS: PRELIMINARY RESULTS

F. Scaldaferri¹, S. Pecere¹, L. R. Lopetuso¹, G. Ianiro¹, L. Laterza¹, E. Schiavoni¹, F. Paroni Sterbini², M. Sanguinetti², L. Masucci², A. Gasbarrini¹, G. Cammarota¹

¹Internal Medicine Department, Gastroenterology Division, Catholic University of Sacred Heart, ²Institute of Microbiology, Catholic University of Sacred Heart of Rome, Rome, Italy

Introduction: Fecal microbiota therapy (FMT) has been successful in treating Clostridium difficile (CDI) colitis, while its possible application in the management of inflammatory bowel disease (IBD) remain unclear.

Aims & Methods: We report preliminary results of an open label feasibility trial on fecal microbiota transplantation in mild to moderate ulcerative colitis. Outpatients affected by active ulcerative colitis (UC) (partial Mayo score ≥4 with an endoscopic Mayo score ≥ 1 with no upper limit on Mayo score), negative for C. difficile toxin were enrolled. Concomitant medications were admitted if stable 2 weeks before and thought the trial. Enrolled patients underwent to colonoscopy and received three administration of FMT using 200 cc of fecal slurry from an healthy donor proposed by the patient, negative for active infections. Primary outcome was feasibility and safety of FMT in UC. Secondary end points were: clinical remission defined as partial Mayo score ≤ 2 with no subscore ≥ 1 and clinical response, defined as reduction of Mayo score of at least 2 points at week 2, 6, 12; endoscopic remission defined as Mayo score = 0 at week 6. Consecutive patients with similar clinical features, candidates to anti-TNF-a or immunosuppressant, acted as a “real life” controls (standard therapy, ST).

Results: We enrolled 8 patients for FMT group and 7 patients for ST. Baseline characteristics were similar between FMT (6M, 2 F; mean age 37 ± 7 yo) and ST group ( 5M, 2 F, mean age 37 ± 10 yo): Pancolitis in 47%, left-side colitis in 33%; 80% were on steroids and 5-ASA, 40% on immunemodulators. In FMT group we observed: 1 SAE (kidney stone) and 2 drop out for disease worsening, while in ST group: 1 SAE (cerebral arterial thrombosis), 2 drop out for disease worsening, 1 infusion reaction. Clinical remission and clinical response for FMT and ST group were respectively: 37.5%/50% and 28.6%/28.6% at week 12, 25%/25% and 14.3%/57.1% at week 2, 25%/50% and 42.8%/42.8% at week 6. Endoscopic remission was observed in 33.3% of FMT group of patients while it was not evaluated in ST group.

Conclusion: The proposed protocol for FMT seems to be safe and well-accepted by UC patients. This FMT protocol have a good potential in inducing clinical response in real life mild-moderate UC patients. Further studies are mandatory.

Disclosure of Interest: None declared

P0377 ROLE OF BMI, USE OF IMMUNE SUPPRESSANT AND PHARMACOKINETIC OF INFLIXIMAB-PATHWAY IN DETERMINING PROSPECTIVE AND RETROSPECTIVE RESPONSE TO THE DRUG IN COHORT OF IBD PATIENTS UNDER MAINTENANCE THERAPY WITH INFLIXIMAB

F. Scaldaferri¹, D. D'Ambrosio¹, D. Curro², V. Petito¹, L. Lopetuso¹, L. Laterza¹, M. T. Pistone¹, A. Poscia³, S. Pecere¹, K. F. Wintgens⁴, C. Berger⁴, E. Schiavoni¹, G. Cammarota¹, A. Milani¹, A. Gasbarrini¹

¹Internal Medicine Department, Gastroenterology division, ²Pharmacology Departmente, ³Hygiene Department, Catholic University of Sacred Heart of Rome, Rome, Italy, ⁴Immundiagnostik, Immundiagnostik, Bensheim, Germany

Contact E-mail Address: valepetito88@gmail.com

Introduction: Response to infliximab (IFX) depends on use of immune suppressants and BMI/body fat content. Few informations however exist on how these factors interact with pharmacokinetics of IFX.

Aims & Methods: Assess a possible correlation between BMI, body fat and use of immunosuppressants with serum IFX, TNF-α and ATI before and after drug administration (trough levels, post-infusion levels). Assess a possible correlation between the serum concentrations of IFX, TNF-α and ATI before and after drug administration (trough levels, post-infusion levels) with the prospective and retrospective clinical response. We enrolled 12 Crohn's disease (CD) patients and 12 ulcerative colitis (UC) patients, in maintenance treatment with IFX, for at least 14 weeks. Blood samples were collected from each patient before infusion of the drug (trough levels) and half hour after the end of the infusion (post-infusion levels). Clinical data were registered 2 months before the infusion (for retrospective analisis) and also 2 months following the infusion (prospective analysis). Trough levels and post-infusion levels of infliximab, TNF-α and anti-infliximab (ATI) were measured by ELISA (Immunodiagnostik). Body fat levels were measured by DEXA.

Results: As expected, higher BMI and body fat levels were associated to reduced response to IFX. Higher IFX trough levels correlated to retrospective response to IFX. ATI associated to lower IFX trough levels and also post-infusion levels. BMI and body fat levels correlated to IFX postinfusion levels, suggesting that IFX does not distribute in the adipose tissue. Patients under immunosuppressant display higher IFX post-infusion levels and reduced ATI levels. The ration between IFX trough levels/TNF-α trough levels predicted the response to IFX at 2 months following IFX infusion.

Conclusion: Patients lacking response to IFX have higher values of body fat and BMI, which directly influence IFX post infusion levels, suggesting that the drug does not distribut in adipose tissue. Immunosuppressants also associate to higher IFX post infusion levels but with lower ATI levels. Finally, for the first time, our study showed that the ratio between IFXtrough-levels and TNF-αtrough-levels in serum, predict clinical response to the drug at 2 months. If confirmed in wider population, the last is a good parameter in order to promote a personalized therapy, based on the study of a specific pathogenic pathway.

Disclosure of Interest: None declared

P0378 INFLIXIMAB TROUGH LEVELS AND ANTI-DRUG ANTIBODIES AFTER INDUCTION PREDICT LONG TERM CLINICAL REMISSION IN INFLIXIMAB-TREATED PATIENTS WITH INFLAMMATORY BOWEL DISEASE

G. Bodini¹, L. Del Nero¹, E. Giannini¹, V. Savarino¹, C. De Maria¹, I. Baldissarro¹, J. Anjali², E. Savarino³

¹Internal Medicine, IRCCS San Martino, Genoa, Italy, ²Research and Development, Prometheus Laboratories, San Diego, United States, ³Suregery, Oncology Gastroenterology, University of Padua, Padua, Italy

Introduction: The treatment paradigm of Inflammatory Bowel Disease is dramatically changed in the past decades, thanks to the development of biological drugs. However, approximately 40% of primary responder patients to anti-TNF therapy experience a loss of response (LOR) during the first year of treatment. Recently, drugs trough levels (TL) and anti-drug antibodies (ADA) presence were proposed as useful tools in the management of patients who have a LOR. Currently, one of the most important issue in IBD patients on biological therapy is to timely identify patients at risk of anti-TNF therapy failure.

Aims & Methods: The aim of our prospective study was to evaluate TL and ADA presence after Infliximab (IFX) induction and their correlation with clinical activity in a series of patients with Inflammatory Bowel Disease (IBD) followed-up for at least 48 weeks. We included 32 consecutive Inflammatory Bowel Disease patients [20 Crohn’s Disease (CD) and 12 Ulcerative Colitis (UC); 17 males, median age 42 years, range 18-69] who underwent IFX therapy and achieved clinical remission after induction (schedule: 5 mg/kg at week 0, 2 and 6). Blood samples were drawn at standardized time points (i.e., 0, 2, 6, and 14 week) before IFX infusion. TL and IFX ADA were measured using an homogenous mobility shift assay (HMSA; Prometheus Lab, San Diego, United States). Disease activity was assessed both at week 14 and week 48 by the Harvey-Bradshaw Index (HBI, remission defined by HBI < 5) in CD patients and by the Mayo score for UC patients (remission defined by Mayo score <2). Also, protein-C reactive and erythrocyte sedimentation rate (ESR) were measured.

Results: During 48 weeks follow-up, 14 patients (43.8%) experienced LOR. We found significantly lower IFX TL after induction in patients who experienced LOR as compared to patients who maintained clinical remission during the follow-up period (0.78 mcg/ml, range 0-14.97 mcg/ml versus 10.01 mcg/ml, range 0.00-42.83 mcg/ml; P=0.0018). Moreover, IFX TL were significantly lower in ADA positive patients as compared to ADA negative ones (0 mcg/ml, range 0-9.66 mcg/ml versus 11.91 mcg/ml, range 2.00-42.83 mcg/ml; P<0.0001). Lastly, ADA concentration after induction was significantly higher in relapsers as compared to patients in remission (3.13 U/ml, range 0-30.52 U/ml versus 0 U/ml, range 0-16.83 U/ml; P=0.02).

Conclusion: Patients who experienced LOR to IFX mono-therapy during long-term follow-up (48 weeks) had significantly lower IFX TL and higher ADA serum concentrations after IFX induction (i.e., 14 weeks). Therefore, assessment of IFX TL and of ADA serum concentrations after IFX induction can be used as a predictive tool for estimating the long-term clinical response to biological therapy.

Disclosure of Interest: None declared

P0379 GRANULO-MONOCYTES APHERESIS INDUCE TGFβ1 MODULATION IN NEUTROPHILS OF PATIENTS SUFFERING FROM ULCERATIVE COLITIS: A POSSIBLE ROLE OF SOLUBLE HLA-I MOLECULES

M. Ghio¹, P. Contini¹, G. Bodini¹, V. Savarino¹, E. Savarino²

¹Internal Medicine, IRCCS San Martino, Genoa, ²Surgery, Oncology and Gastroenterology, Padua University, Padua, Italy

Contact E-mail Address: bodini.giorgia@gmail.com

Introduction: Plasmapheresis is used in immune-mediated disease in order to remove humoral factors and, in addition, to modulate cellular immunity. It has been shown that during aphaeretic centrifugation, whole and/or re-folded soluble HLA class I molecules (sHLA-I) bind to the circuit surfaces. Similarly, neutrophils can bind sHLA-I molecules with immunoglobulin-like transcript (ILT) membrane receptors, becoming hereafter sensitive to the immunomodulation of sHLA-I such as transcriptional and post-transcriptional transforming growth factor (TGF)-β₁ modulation. On the other hand, TGFβ signaling plays a major role in the pathogenesis of inflammatory bowel diseases and it is known to directly induce Foxp3 expression. Besides, Foxp3 expression has been reported increased in patients who responded to granulocytes apheresis with remission of clinical symptoms.

Aims & Methods: The aim of this prospective study was to evaluate a possible sHLA-I mediated immunomodulation in granulocytes and monocytes apheresis in ulcerative colitis patients who responded to therapy. We prospectively enrolled a total of 10 patients (4M/6F; mean age 49, range 27-73) who achieved clinical remission with GMA. The GMA sessions (5 cycle/session) were performed using Adacolumn device. Instantly before each single apheresis and immediately after each procedure, neutrophils were analyzed for a possible in vivo aftermath of sHLA-I binding with corresponding ligands Ig-like-transcripts. The concentrations of sFasL molecules were determined by double-determinant immunoassay (DDIA) and the concentrations of TGFb₁ were determined by double-determinant immunoassays utilizing a commercially available kits.

Results: Between every GMA cycle a significant upregulation of intracytoplasmic TGFβ₁ molecule or TGFβ₁-mRNA was observed in neutrophils and CD8⁺ T lymphocytes drawn along the apheretic therapeutic treatments. In particular, the greatest mean increase was found after the first and the forth GMA cycles (from +1% to +30%). A significant up-regulation of sFasL and TGFβ1 concentrations in plasma was observed along the procedures. Similarly, the mean difference increases in comparison with previous samples were constantly found raising during scheduled blood sampling for both molecules. In CD4⁺ T lymphocytes, unable to bind sHLA-I, the aphaeretic procedures never induced TGFβ₁ modulation

Conclusion: Our findings suggest that the immunosuppressive effects following therapeutic apheresis might at least in part depend on activated leukocyte sensitivity to sHLA-I molecule bioactivity.

Disclosure of Interest: None declared

MONDAY, OCTOBER 26, 2015   09:00-17:00

OTHER LOWER GI DISORDERS I – HALL 7__________

P0380 PREDICTIVE FACTORS OF IN-HOSPITAL AND SHORT-TERM MORTALITY ISCHEMIC COLITIS

A. Peixoto¹, M. Silva¹, R. Gaspar¹, R. Morais¹, P. Pereira¹, G. Macedo¹

¹Gastroenterology, Centro Hospitalar de São João, Porto, Portugal

Contact E-mail Address: armandoafp5@gmail.com

Introduction: Ischemic colitis is the most common form of intestinal ischemia with a wide spectrum of severity, with possible risk of death.

Aims & Methods: Evaluate predictive factors of in-hospital and short-term mortality, in a cohort of patients with ischemic colitis. Retrospective analysis of ischemic colitis cases diagnosed between 2008 and 2013 in a single center, with assessment of factors at diagnosis associated with in-hospital mortality and at 3 months.

Results: Of the 203 patients included (132 women), 47 (23%) died during the follow-up (median: 16 months). 21 (45%) died during hospitalization and at three months there were 30 deaths (64% of total). In the univariate analysis, higher values of LDH (p=0.004), urea (p < 0.001), creatinine (p=0.001) and leukocytes, more days of hospitalization (p=0.006), male gender (p=0.006), atrial fibrillation (AF) (p=0.03), intestinal occlusion (p < 0.001), recent intravascular intervention (p=0.001), endoscopic severity (p=0.02) need for surgery (p < 0.001) or vasopressor support (p < 0.001), parenteral nutrition (p < 0.001) or antibiotic use (p=0.013), prophylactic anticoagulation (p=0.02) and hospitalization in intermediate/intensive care (ICU) (p < 0.001) were associated with in-hospital mortality. In the multivariate analysis, AF, vasopressor support and ICU admission for in-hospital mortality. These factors have been used for the creation of a risk score that showed high acuity with an area under the curve (ROC) of 0.89 (S=89%; E=78% - mortality 32%). At 3 months, the presence of chronic renal failure (p=0.002) and lower values for hemoglobin (p=0.006) at admission were also independently associated with mortality.

Conclusion: Multiple clinical and analytical factors at admission were associated with in-hospital mortality, and the presence of AF, vasopressor support or admission in ICU proved to be independent factors (risk score probability of 32%). The mortality rate at 3 months presented similar risk factors.

Disclosure of Interest: None declared

P0381 ISCHEMIC COLITIS: THE EXPERIENCE OF A REFERRAL TERTIARY CENTER

A. Peixoto¹, M. Silva¹, R. Gaspar¹, R. Morais¹, P. Pereira¹, G. Macedo¹

¹Gastroenterology, Centro Hospitalar de São João, Porto, Portugal

Contact E-mail Address: armandoafp5@gmail.com

Introduction: Ischemic colitis is the main form of intestinal ischemia, especially in the elderly population, it is essential to have an early diagnosis with subsequent treatment.

Aims & Methods: Evaluate the demographics, etiology, clinical manifestations and prognosis of ischemic colitis in a referral tertiary center. Retrospective analysis of patients with ischemic colitis histologically confirmed between 2008 and 2013.

Results: 205 patients included (64% women), mean age of 75 years. Median follow-up time of 16 months, with an overall mortality rate of 22%. The majority of patients was admitted in the emergency department (88%) and presented with rectal bleeding and/or abdominal pain (87%). The main medical problems were HTA (65%), diabetes mellitus (24%), cerebrovascular disease (21%), heart failure (18%), coronary artery disease (17%), renal failure (15%) and atrial fibrillation (10%). The most prevalent medications were antihypertensives, diuretics and aspirin/NSAID. At admission, the majority presented with leukocytosis and renal dysfunction, without anemia. The diagnosis was established by colonoscopy in the majority of cases (87%), with a correlation of 94% with the histology. Urgent surgery was necessary in 11% of cases (due to peritonitis in half of them) and 12% of patients required blood transfusions. The main complication reported was acute kidney injury (10%). 80% underwent antibiotic therapy. The median length of hospital stay was 8 days, with need for intermediate/intensive care in 19% of cases. The in-hospital mortality rate, at 30 days and at 3 months was 9%, 10% and 14%, respectively. The recurrence rate was 6.5%.

Conclusion: We observed a high incidence of ischemic colitis in the elderly females, especially in the presence of cardiovascular risk factors. Colonoscopy was the preferred method of diagnosis. The vast majority recovered after medical support. The in-hospital mortality represents approximately half of the overall mortality.

Disclosure of Interest: None declared

P0382 ENDOSCOPIC BAND LIGATION (EBL) IS SUPERIOR TO ENDOSCOPIC CLIPPING FOR THE TREATMENT OF COLONIC DIVERTICULAR HEMORRHAGE

A. Yamauchi¹, K. Watanabe¹, S. Yazumi¹

¹Division of Gastroenterology and Hepatology, Digestive Disease Center, Kitano Hospital, Osaka, Japan

Contact E-mail Address: atsushi7200@gmail.com

Introduction: Colonic diverticular hemorrhage is a common cause of lower gastrointestinal bleedings. However, low detection rate of a responsible diverticulum for bleeding, less than 20%, and high early re-bleeding rate, more than 30%, are clinical problems. Recently, there were several reports of high successful rate of endoscopic band ligation (EBL) for colonic diverticular hemorrhage. Therefore, we retrospectively compared the efficacy of hemostasis for colonic diverticular hemorrhage in our hospital.

Aims & Methods: From April 2012 to March 2015, total 149 cases of 90 patients in whom colonic diverticular hemorrhage was diagnosed or clinically suspected (mean age 73.5 years (41-95 years); male: 66, female: 24) were retrospectively enrolled. Urgent colonoscopy was performed within 24 hours from arrival to our hospital by colonoscopy with a water-jet function. To better identify a responsible diverticulum, a transparent soft hood (Olympus Optical Co, Ltd, Tokyo, Japan) was attached to the tip of the scope. Diverticular hemorrhage was definitely diagnosed when active bleeding from a diverticulum, a visible non-bleeding vessel within a diverticulum, or a densely adherent clot despite vigorous irrigation, was recognized. After identifying a responsible diverticulum a marker clip was placed near the diverticulum. Hemostasis was selected from following three methods; closing an orifice of the responsible diverticulum with clipping device (closing method); clipping a vessel within a diverticulum (clipping method); EBL (Sumitomo Bakelite Co Ltd, Tokyo, Japan) method. Early re-bleeding rates within a week were evaluated.

Results: Colonic diverticular hemorrhage was diagnosed in 55 of 149 cases (36.9%); active bleeding in 46, non-bleeding visible vessels in 4, and a densely adherent clot in 5 cases. Hemostatic treatments were done in 53 of 55 cases; closing method in 20, clipping method in 27, and EBL method in 6. Residual 2 cases could not received hemostatic treatment because of inappropriate cases for endoscopic hemostasis. Respective re-bleeding rates within a week were 11 (55%), 10 (37%), and 0 (0%). There was a significant difference of re-bleeding rate between closing and EBL methods (p=0.02), although no significant difference was found between clipping and EBL methods (p=0.145). There was no significant adverse event related to endoscopic hemostasis. One case refractory to closing method required surgery.

Conclusion: EBL would be safe, effective, and superior to hemoclips for the treatment of colonic diverticular hemorrhage. The hood method is useful to identify the responsible diverticular hemorrhage.

Disclosure of Interest: None declared

P0383 POST-POLYPECTOMY BLEEDING: FACTORS ASSOCIATED AND ROLE OF THIENOPYRIDINES

F. Pigo'¹, H. Bertani¹, M. Manno¹, A. Caruso¹, V. G. Mirante¹, C. Barbera¹, S. Mangiafico¹, A. M. Rebecchi², R. L. Conigliaro¹

¹Endoscopy Unit, New Civil Hospital, Baggiovara, Modena, Italy, Modena, ²Internal Medicine, Regina Margherita Hospital, Castelfranco Emilia, Italy

Contact E-mail Address: f.pigo@ausl.mo.it

Introduction: Limited data exist for clinically significant (that requires transfusion or hospitalization) post-polypectomy bleeding (PPB) risk factors and the role of thienopyridines (ticlopidin, clopidogrel, prasugrel, ticagrelor).

Aims & Methods: To determine factors associated with PPB and if thienopyridines use prior to colonoscopy increases the risk of clinically significant PPB. A case-control study of patients with clinically significant PPB was performed at our Hospital. Information collected included age, gender, uninterrupted assumption (within five days of colonoscopy) of thienopiridines, aspirin, low weight molecular eparine (LWMH), comorbidities, polyp characteristics, and polypectomy technique. The control group consisted of patients matched with the controls for the same characteristics

Results: During the study period (from 2007 to 2014), 15,946 patients underwent colonoscopy with polypectomy at our institutions and 84 patients presented with clinically significant PPB. Three patients were excluded from analysis because of lack of informations about the patient. The remaining 81 patients with removal of 130 polyps (32 immediated bleeding and 49 delayed bleeding) were well matched to 443 patients who had undergone colonoscopy with 855 polypectomies without complications. Uninterrupted thienopyridine use prior to polypectomy was 5% in the bleeding group and 7% in the control group. Mean ± standard deviation dimensions of polyps wiht PPB and in the control group was 18.4 mm ± 15 mm and 7.7 ± 7.9 mm respectively. Median size of polyps removed during thienopyridine assumption was 7.5 mm. According to a multivariate logistic regression analysis that included significant factors from the univariate logistic regression and known risk factors for bleeding, polyps superior than 10 mm (OR 3.6; 95% CI 2.1-6.2; P <0.0001), polyps located in the right colon (OR 2.13; 95% CI 1.3-3.4; P = 0.003) aspirin use (OR 7.7; 95% CI 3.2-18.7; P < 0.0001) and LWMH use (OR 10.8; 95% CI 5.6-20.7; P <0.0001) were significantly associated with the development of PPB. Polypectomies under thienopyridine showed a positive association without significance (OR 1.4; 95% CI 0.3-7.0; P = 0.6) possibly for minor dimensions of the polyps removed. Preventive measures for bleeding were found to be protective for only immediate PPB (OR 3.7; 95% CI 1.4-9.3; P = 0.005).

Conclusion: Polypectomies under thienopyridines are safe for polyps less than 10 mm. Polyp ≥10mm, located in the right colon, aspirin or LWMH is associated to PPB while prophylactic clip are protective only for immediate bleeding.

Disclosure of Interest: None declared

P0384 CAUSES OF HEMATOCHEZIA AND ANTIBIOTIC-ASSICIATED COLITIS IN CHILDREN AND ADOLESCENTS

L. Stampfer¹, E. Brandstätter², A. Deutschmann¹, E. Dür¹, F. Eitelberger², T. Fürpass³, G. Gorkiewicz⁴, P. Heinz-Erian⁵, I. Heller⁶, K. Herzog¹, B. Hopfer⁷, R. Kerbl⁷, E. Klug⁸, R. Krause⁹, E. Leitner¹⁰, C. Mache¹, T. Müller⁵, J. Pansy¹¹, M. Pocivalnik¹, G. Schweintzger¹², E. Sterniczky¹³, E. Zechner¹⁴, A. C. Hauer¹, C. Högenauer⁹, K. M. Hoffmann¹

¹Pediatrics, Medical University Graz, Graz, ²Pediatrics, Hospital Wels-Grieskirchen, Wels, ³Microbiology, Hospital Leoben, Leoben, ⁴Pathology, Medical University Graz, Graz, ⁵Pediatrics, ⁶Microbiology, Medical University Innsbruck, Innsbruck, ⁷Pediatrics, Hospital Leoben, Leoben, ⁸Pathology, Hospital Oberwart, Oberwart, ⁹Internal Medicine, ¹⁰Microbiology, ¹¹Neonatology, Medical University Graz, Graz, ¹²Neonatology, Hospital Leoben, Leoben, ¹³Pediatrics, Hospital Oberwart, Oberwart, ¹⁴Molecular biology, Karl-Franzens-Universität, Graz, Austria

Contact E-mail Address: laura.stampfer@stud.medunigraz.at

Introduction: Diseases causing hematochezia in children are diverse and range from benign to potentially life-threatening. Systematic pediatric data on the causes of hematochezia are scarce. We aimed at elucidating the range of disorders causing hematochezia in children. A second aim was to investigate antibiotic-associated colitis (AAC) presenting with hematochezia, focusing on antibiotic-associated hemorrhagic colitis (AAHC), a recently described entity caused by Klebsiella (K.) oxytoca.

Aims & Methods: Infants, children and adolescents with visible bloody stool were recruited at 5 Austrian pediatric hospitals. Patients were grouped in infants (<1 year), young children (1-5 years), children (6-13 years) and adolescents (≥14 years). As an addition to routine diagnostics a stool culture for K. oxytoca was done (API 20E test). Further clinical investigations or therapy were not influenced by the study. We collected data on history, laboratory findings, infectiological investigations, imaging, final diagnosis and clinical course.

Results: We included 221 patients (female n=102, 46%): 57 infants, 64 young children, 46 children and 54 adolescents. 17 (7.7%) had a positive stool culture for K. oxytoca. In 129 (58%) hematochezia was caused by infectious diseases. In 51 (23%) no final diagnosis could be made and hematochezia resolved spontaneously. Thirty (14%) patients underwent endoscopy, which led to a definite diagnosis in 17/30 (57%). 21 (9.5%) were diagnosed with diseases occurring only once or twice within this study. The most common diagnoses in regard to age groups were: Food protein-induced proctocolitis in infants (n=19, 33%), bacterial enterocolitis (Campylobacter/Salmonella; n=34, 53%) in young children and inflammatory bowel disease in children (n=10, 22%) and adolescents (n=11, 20%). AAC was diagnosed in 12 (5%) patients: 2 infants with AAHC, 2 young children with C. difficile; in the remaining 8/12 (67%) with the clinical diagnosis of AAC no known pathogen was identified.

Conclusion: Hematochezia was caused by infections in the majority of patients. In most patients invasive diagnostic procedures were not necessary. Thus, in children with hematochezia indication for endoscopy should be restrictive, especially in infants and young children. AAC presenting with hematochezia might be caused by pathogens other than C. difficile and K. oxytoca. AAHC, caused by K. oxytoca, was a rare diagnosis in our pediatric cohort.

Disclosure of Interest: None declared

P0385 EFFICACY OF CT DIAGNOSIS OF LOWER GI BLEEDING WITH ISCHEMIC COLITIS

M. Hirayama¹, T. Minagawa¹, R. Fujii¹, S. Fujie¹, T. Kondo², T. Kimura¹³, H. Ihara¹³, T. Sumiyoshi¹, Y. Tsuji², N. Yoshizaki¹, H. Kondo¹

¹Department of Gastroenterology, ²Department of Oncology, Tonan Hospital, ³4th Department of Internal Medicine, Sapporo Medical University, Sapporo, Japan

Contact E-mail Address: otarugi@gmail.com

Introduction: Ischemic colitis (IC) is one of the most frequent causes of sudden bloody bowel discharge, melena. It is generally accepted in Japan to perform emergency colonoscopy (E-CS) for detection of causative lesion of melena, and as necessary, endoscopic treatment for the bleeding from such lesions as diverticulum, tumor etc. However, for IC, such as endoscopic intervention is rarely needed because the bleeding quite often spontaneously ceases. Thus, less invasive modality than CS which is useful only for diagnosis would be much beneficial for IC patients with melena. Edematous swelling of colon wall on CT has been widely accepted as a target sign of IC.

Aims & Methods: In the present study, its diagnostic value for IC was elucidated. 249 patients with a complaint of melena were enrolled and target sign in 177 patients who underwent both CT and CS were analyzed. The Toshiba Aquilion64 (64DAS) CT scanner was used for CT. Scans were acquired with use of 130kVp, 0.5 s/rot and 0.5mmx64 HP53, respectively. Images were retrospectively reconstructed by using a 0.5 mm section index.

Results: Of 177 patients, 94 showed typical sign of IC on CS. Of these 94 patients, 80 were demonstrated to have a target sign on CT (85.1% sensitivity). Of 83 patients who were negative for CS sign, 72 patients were target sign free (86.7%specificity). When the analysis was carried out on only those patients who received CS within 48hrs, sensitivity increased to 92.9%(75/83).

Conclusion: CT at an early stage after the episode of melena showed similar sensitivity and specificity as E-CS for detection of IC. Thus this less invasive modality can be used, replacing E-CS for patients with IC.

Disclosure of Interest: None declared

P0386 THE HISTORY OF COLONIC DIVERTICULAR HEMORRHAGE AND COLONOSCOPIC HEMOSTASIS ARE INDEPENDENT PREDICTORS FOR RECURRENT HEMORRHAGE

M. Wada¹, M. Kato¹, E. Sakaguchi¹, Y. Ishibashi¹, S. Banno¹, K. Abe¹, Y. Takada¹, T. Hirata¹, Y. Takatori¹, S. Kinoshita¹, K. Takabayashi¹, M. Kikuchi¹, M. Kikuchi¹, Y. Fujiyama¹, M. Suzuki¹, T. Uraoka¹

¹Department of Gastroenterology, National Hospital Organization Tokyo Medical Centre, Tokyo, Japan

Contact E-mail Address: michikosato@ntmc.hosp.go.jp

Introduction: Colonic diverticular hemorrhage (CDH) is a common health care problem, and it is reported to occupy 40% of lower gastrointestinal hemorrhage. Although it is often self-limited and eventually ceases spontaneously in up to 70-90% of cases, recurrence of CDH is not so rare and it occurs in about 30%. It has also been reported that once hemostasis was obtained for CDH endoscopically, recurrent hemorrhage significantly decreases (Jensen et al. N Engl J Med 2000). However, it is not easy to perform colonoscopy urgently, and therefore, narrowing down candidates is necessary who would be more benefited by colonoscopy from the viewpoint of long-term outcome.

Aims & Methods: The aim of this study was to clarify risk factors of recurrent CDH.This was a retrospective cohort study from a tertiary hospital. A total of 265 patients who were diagnosed as CDH from March 2004 to October 2014 were enrolled. CDH was defined as apparent hematochezia in patients with known colonic diverticulum diagnosed by computed tomography, colonoscopy, and/ or barium enema examination without any other causes. We analyzed the association between patients’ characteristics (age, gender, history of CDH, arteriosclerotic disease, antiplatelet use, anticoagulant use, to be obtained hemostasis by colonoscopy) and recurrence of CDH using Cox proportional hazards model. The cumulative recurrent curve was plotted using Kaplan-Meier methods.

Results: Of 265 patients, 170 were men and 95 were women, and median age was 75 [IQR 63-83]. The median observation period was 276 [IQR 29-1047] days. A total of 227 patients underwent colonoscopy while hospitalized, and 22 patients (10%) obtained colonoscopic hemostasis. One patient obtained hemostasis by interventional radiology. The other patients eventually obtained spontaneous hemostasis. Recurrent CDH was seen in 54 patients (20%). Univariate analysis showed significant association of history of CDH and colonoscopic hemostasis with recurrent CDH. Multivariate analysis showed that history of CDH is an independent risk factor for recurrent CDH (OR 2.26 [95%CI 1.15-4.16], p=0.0192), and obtained colonoscopic hemostasis independently reduces recurrent CDH (OR 0.30 [95%CI 0.05-1.0], p=0.0492). One year cumulative recurrent hemorrhage rate was 35% in those with history of CDH, whereas 15% in those without (log rank test, p=0.0047).

Conclusion: History of CDH and colonoscopic hemostasis were independent predictors for recurrent CDH. Although the identification rate of bleeding point remained only 10%, colonoscopic hemostasis could reduce 70% of recurrent hemorrhage. Therefore, patients with past history of CDH should be aggressively considered to undergo urgent colonoscopy, since they are at high risk for recurrent CDH.

Disclosure of Interest: None declared

P0387 DIABETES MELLITUS IS A PREDICTIVE FACTOR OF THE DIVERTICULAR RE-BLEEDING OF THE COLON IN JAPANESE PATIENTS

T. Sugiyama¹, M. Ebi¹, K. Adachi¹, S. Gouji¹, N. Okaniwa¹, Y. Yamaguchi¹, T. Yosimine¹, H. Noda¹, A. Tanabe¹, K. Yanamoto¹, Y. Kondo¹, Y. Ito¹, S. Izawa¹, Y. Funaki¹, N. Ogasawara¹, M. Sasaki¹, K. Kasugai¹

¹Gastroenterology, Aichi Medical University School of Medicine, Nagakute, Japan

Contact E-mail Address: yes.handball@gmail.com

Introduction: Diverticular bleeding of the colon occurs in 2-4% of colonic diverticula diseases and it has been reported to be the most common cause of lower gastrointestinal bleedings. In general, the treatment strategy for diverticular bleeding of the colon is endoscopic hemostasis or interventional radiology (IVR) in cases of the colonic diverticula in which bleeding points are able to be detected. However, it is difficult to precisely detect the bleeding point in most of diverticular bleedings by colonoscopy or enhanced computed tomography. There have been few reports regarding the recurrence of diverticular bleeding, and the rate of recurrence of diverticular bleedings was reported from 10.8 to 43.4%. However, the risk factors of recurrent bleedings of colonic diverticula are still unknown. Thus, we assessed the risk factors of recurrent bleedings to estimate the prognosis of the patients with bleeding colonic diverticula.

Aims & Methods: We aimed to investigate the risk factors of diverticular re-bleeding in the colon. Ninety-three patients who were referred to our hospital due to lower gastrointestinal bleeding and were diagnosed as colonic diverticular bleeding between January 2008 and December 2014 were analyzed. The patients with melena or hematochezia who had no other bleeding lesions except for colonic diverticula were diagnosed as diverticular bleeding by colonoscopy. Ninety-three patients were divided into two groups; 38 patients without repeated diverticular bleeding, non-recurrence group; 55 patients requiring more than two hospitalizations due to diverticular bleeding, recurrence group). Patients’ backgrounds such as sex, age, comorbidities and use of medicines were compared between the two groups.

Results: Thirty-eight patients (40.9%) (24 men and 14 women; median age, 70.4 ± 11.0 years old) were included in the recurrence group. Antiplatelet or anticoagulant drugs were administered in 14 patients (38.8%), and NSAIDs were administered in 4 patients (10.5%). Ten patients (26.3%) had diabetes mellitus, 3 patients (7.9%) had ischemic heart diseases. On the other hand 55 patients (59.1%) (33 men and 22 women; median age, 73.7 ± 10.5 years old) were included in the non-recurrence group. Antiplatelet or anticoagulant drugs were administered in 17 patients (30.9%), NSAIDs were administered in 3 patients (5.4%). Five patients (9.1%) had diabetes mellitus, 7 patients (12.7%) had ischemic heart diseases. Univariate analysis revealed that the patients with diabetes mellitus significantly harbored higher frequency of diverticular re-bleeding than those without diabetes mellitus (p=0.043). However, there were no significant differences in other factors between the two groups. Multivariate analysis showed that diabetes mellitus was an independent and significant predictor for diverticular re-bleeding of the colon (odds ratio, 3.60; 95% confidence interval, 1.1-11.8; p=0.035).

Conclusion: Patients with diabetes mellitus harbored about a 4-fold higher risk of diverticular re-bleeding compared with patients with other comorbidities. Patients with diabetes mellitus suggested to be carefully observed after initially diverticular bleeding.

Disclosure of Interest: None declared

P0388 ANTITHROMBOTIC AGENTS AND POST-POLYPECTOMY BLEEDING

T. Kubo¹, K. Yamashita¹, Y. Einami¹, I. Yamamoto¹, K. Onodera¹, E. Yamamoto¹, K. Nosho¹, Y. Arimura¹, Y. Sato², M. Nojima³

¹Department of Gastroenterology, ²Department of Clinical Oncology and Hematology, Sapporo Medical University, Sapporo, ³Center for Translational Research, The Institute of Medical Science Hospital, The University of Tokyo, Tokyo, Japan

Contact E-mail Address: kubo-t@grape.plala.or.jp

Introduction: It is still controversial whether antithrombotic agents, i.e., antiplatelets and anticoagulants, increase post-polypectomy bleeding (PPB).

Aims & Methods: The aim of this study was to elucidate risk factors for PPB including antithrombotic agents.This was a case-control study based on medical records of single center. PPB was defined as bleeding that occurred 6 hours to 10 days after colonoscopic polypectomy and required endoscopic hemostasis. All colonoscopic polypectomies performed between January 2011 and December 2014 were reviewed.

Results: PPB occurred in 29 (3.7%) of 788 polypectomies performed during the period. Four PPB cases required transfusion and no PPB cases required surgery. Any antiplatelets or anticoagulants were prescribed to 210 (26.6%) patients; antiplatelets to 155, anticoagulants to 83 and both to 28 patients. All anticoagulants and antiplatelets except for aspirin or cilostazol in 19 cases were ceased before polypectomy. Anticoagulants were significantly associated with PPB (P < 0.0001) while antiplatelets were not. Bridging therapy using intravenous unfractionated heparin was adopted to 73 patients and also significantly correlated with PPB (P < 0.0001). None of the followings correlated with PPB; age, gender, polyp location, size, shape (flat vs. sessile vs. pedunculated), histology, number of polyps resected, prophylactic clipping, resection method (polypectomy vs. endoscopic mucosal resection vs. endoscopic submucosal dissection). Thromboembolic event occurred in one patient taking anticoagulant after cessation.

Conclusion: Patients taking anticoagulants have increased risk of PPB, even if anticoagulants are interrupted before polypectomy. Heparin-bridge therapy might be responsible for the increased PPB in patients taking anticoagulants.

Disclosure of Interest: None declared

P0389 COST-EFFECTIVENESS OF ROUTINE SCREENING FOR LYNCH SYNDROME IN COLORECTAL CANCER PATIENTS UP TO 70 YEARS OF AGE

A. Goverde¹², C. H. Leenen¹, E. W. de Bekker-Grob³, A. Wagner², M. G. van Lier¹, M. C. Spaander¹, M. J. Bruno¹, C. Tops⁴, A. M. van den Ouweland², E. J. Dubbink⁵, E. J. Kuipers¹⁶, W. N. Dinjens⁵, M. E. van Leerdam¹⁷, E. W. Steyerberg³, on behalf of LIMO study group

¹Gastroenterology & Hepatology, ²Clinical Genetics, ³Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, ⁴Clinical Genetics, Leiden University Medical Center, Leiden, ⁵Pathology, ⁶Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, ⁷Gastroenterology & Hepatology, Antoni van Leeuwenhoek Hospital, Netherlands Cancer Institute, Amsterdam, Netherlands

Contact E-mail Address: a.goverde.1@erasmusmc.nl

Introduction: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC). Identifying LS carriers among CRC patients is of great importance, since surveillance programs for their affected relatives can reduce CRC morbidity and mortality by 56-70%. However, many LS carriers are still not identified. The aim of this study was to assess the cost-effectiveness of routine molecular screening for LS in CRC patients up to 70 years of age.

Aims & Methods: A population-based series of CRC patients aged ≤70 years was routinely screened for LS by analysis of microsatellite instability, immunohistochemistry and MLH1 hypermethylation, followed by germline mutation analysis in indicated cases. Effectiveness of screening was expressed in life years gained (LYG), based on the number of LS carriers detected among CRC patients and their relatives. Total costs consisted of LS diagnostics and surveillance, including gynaecological surveillance and prophylactic surgery for female LS carriers. We calculated incremental cost-effectiveness ratios (ICERs) comparing different age cut-offs and comparing age-targeted screening with the revised Bethesda guidelines. One-way sensitivity analyses were performed to test the robustness of ICERs.

Results: Screening among 1117 CRC patients identified 23 LS carriers, of whom 7 were ≤50, 7 were 51-60 and 9 were 61-70 years of age. Additionally, 70 LS carriers were identified among relatives (14, 42 and 14 per age category respectively). Overall, screening amounted to 68.1 LYG or 14.4, 39.1 and 14.6 LYG per age category. Total costs for LS screening and surveillance increased from €232,395 (€11,066 per LS carrier detected) for LS screening among CRC patients ≤50 years of age to €1,056,191 (€11,357 per LS carrier detected) for screening CRC patients ≤70 years of age. ICERs were €12,941/LYG for LS screening in CRC patients ≤60 years compared with ≤50 years and €21,728/LYG for screening CRC patients ≤70 years compared with ≤60 years. The revised Bethesda guidelines identified 17/23 (74%) LS carriers among CRC patients and 53/70 (76%) LS carriers among relatives. The ICER for LS screening in CRC patients ≤70 years of age was €22,485/LYG compared with LS screening according to the revised Bethesda guidelines. The ICERs were most sensitive to the assumed LYG by relatives. All ICERs remained <€30,000/LYG in sensitivity analyses.

Conclusion: Routine LS screening by analysis of microsatellite instability, immunohistochemistry, and MLH1 hypermethylation in CRC patients up to 70 years of age is a cost-effective strategy according to currently accepted standards, with important clinical benefits for LS carriers among CRC patients and their relatives.

Disclosure of Interest: None declared

P0390 CEA AND CYFRA21-1 IMPROVE THE SPECIFICITY OF A 29-GENE BLOOD-BASED TEST FOR EARLY DETECTION OF COLORECTAL CANCER

C. Nichita¹, S. Hosseinian², S. Monnier-Benoit², L. Ciarloni², G. Dorta¹, on behalf of DGNP-COL-0310 study group

¹Gastroenterology and Hepatology Department, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, ²Novigenix, Epalinges, Switzerland

Contact E-mail Address: laura.ciarloni@novigenix.com

Introduction: An effective and convenient test for colorectal cancer (CRC) screening is needed in order to increase compliance and reduce mortality from CRC. Recent studies^1,2 demonstrate that an effective blood test could be an attractive alternative to increase participation rate to CRC screening. Previously³ we validated a novel blood test for the detection of CRC and large adenomas based on a 29-gene panel in peripheral blood mononuclear cells.

Aims & Methods: The aim of this study was to investigate how addition of CEA, CYFRA21-1, CA125 and CA19-9, circulating protein tumor biomarkers used in the management of different cancers, could improve accuracy of the 29-gene test.

Subject enrolled in the DGNP-COL-0310 study, a multi-center case-control study previously described³, were older than 50 years and referred for screening/diagnostic colonoscopy or scheduled for surgical removal of CRC. 371 plasma samples from the Swiss participants, including 118 samples from CRC patients, 103 from patients with adenomas ≥1cm and 150 from subjects without colorectal lesions (controls), were used to measure protein concentration on the Architect platform (Abbott Diagnostics). Subjects were assigned to training, validation, and test set, using the same design used to develop the 29-gene classifier. Training and validation set were used to select the most relevant circulating protein tumor markers and to determine a new predictive algorithm combining the protein biomarkers with the existing 29-gene classifier. The test set was used to validate the predictive algorithm on the independent data set.

Results: Among the 4 tested proteins, CEA and CYFRA21-1, alone or in combination, showed the highest predictive accuracy for CRC discrimination and were included in the final predictive algorithm. When validated on an independent test set, including 73 CRC, 42 adenomas and 74 controls, the algorithm showed a specificity of 92% and a sensitivity of 78% for CRC and of 52% for adenoma detection.

Conclusion: The addition of the tumor biomarkers CEA and CYFRA21-1 improved the specificity of our 29-gene algorithm, which increased from 88% to 92%. Sensitivity for CRC and large adenomas increased only slightly. Thus, we confirmed that this blood test could be an effective complement to colonoscopy to increase compliance to CRC screening. The test has now been launched on the Swiss market under the trade name Colox®.

Disclosure of Interest: C. Nichita: None declared, S. Hosseinian Shareholder: Own shares of Novigenix, Conflict with: Employee of Novigenix, S. Monnier-Benoit Shareholder: Own shares of Novigenix, Conflict with: Employee of Novigenix, L. Ciarloni Shareholder: Own shares of Novigenix, Conflict with: Employee of Novigenix, G. Dorta Consultancy: Consultant of Novigenix

P0391 NEW HORIZONS IN T1 CANCERS: DIFFERENT METASTATIC RISK PARAMETERS ARE PROBABLY NEEDED FOR CRC SCREENING POPULATIONS

E. Rosa-Rizzotto¹, E. Guido¹, D. Caroli¹, M. Lo Mele², R. Cappellesso², M. Rugge², E. Tessari³, A. Frasson³, P. Pilati³, F. De Lazzari¹

¹Gastroenterology Unit, ²Surgical Pathology and Cytopathology Unit, ³Surgery Unit, Padova, Italy

Contact E-mail Address: erik.rosarizzotto@gmail.com

Introduction: Actually we don’t know how long does it takes for a preneoplastic lesion to become a cancer invading the submucosal layer (pT1). We don’t know, also, how long a pT1 lesion rest in the submucosal layer before going deeper to reach the muscolaris propria becoming pT2. At present, in these neoplasic lesions hystological parameters alone determine wether a low (7%) or high (35%) risk of metastasis exists^1,2.

Aims & Methods: The aim of this study was to assess the metastatical risk in pT1 lesions diagnosed during routine colonoscopies (RC) in comparison with those found during CRC screening colonoscopies (SC). We retrospectively reviewed the files of 17587 colonscopies (8343 RC and 9244 SC) performed in our Endoscopy Unit from july 2009 to january 2015 and extracted all the pT1 CRC. pT1 patients gone for a strict follow-up: first visit in 6 months, then a visit every year. The schedule was: physiscal examination, CEA marker and colonscopy every year, CT scan and liver Ultrasonograpy every other year.

Results: In 67 months 144 pT1 (80M, 55F) tumors were detected, 115(79.9%) during SC and 29(20.1%) during RC. The median follow-up was 39 months. Overall pT1 prevalence was 115/9244(1.2%) in SC and 29/8343(0.3%) in RC (Pearson χ²=43.4, p<.0001). 71(49%) patients undergone for surgery because considered at high metastatic risk, 3 refused. During the follow-up only 5 patients (5/144, 3.4%) presented limphnode metastasis. In high-risk group 2/7 (28%) in RC and 3/61 (4.7%) in SC presented metastatsis (Pearson χ², p=0.019). No patient 0/73 with low metastatic risk presented metastsis during follow-up. Population mean age was higher in RC 72 vs 62 (p < 0.00001). High risk pT1 were more frequent in SC (53% vs 24%, p < 0.01). No differences were found in the two populations for: dimension, tumor grading, deep/extent of invasion, vascular invasion, budding, polypectomy resection margin (p=ns). Presence of tumor budding was higher in male (21% 16/77 vs 5% 3/61, p=0.006). Survival curves for metastatic risk shows a non significative difference between SC and RC (Breslow test χ²⁼1.528, p=0.216; Long Rank Mantel-Cox χ²⁼1.137, p=0.286).

Conclusion: CRC pT1 are 4 times more frequent in SC than in RC. However, only in the RC group the real risk of limph node metastsis justfy the surgical resection. In the SC one, the present series highlighted a remarkable overtreatment and the pressing need to identify new parameters more strongly associated to limph node metastasis in this kind of patients.

Disclosure of Interest: None declared

P0392 FIT-BASED COLORECTAL CANCER SCREENING: DO WE NEED TO TAILOR SCREENING FOR MEN AND WOMEN?

E. J. Grobbee¹, E. Wieten¹, E. Stoop¹, T. R. de Wijkerslooth², I. Lansdorp-Vogelaar³, P. M. Bossuyt⁴, E. Dekker², E. J. Kuipers¹, M. C. W. Spaander¹

¹Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, ²Gastroenterology and Hepatology, Academic Medical Centre Amsterdam, Amsterdam, ³Public Health, Erasmus MC University Medical Center, Rotterdam, ⁴Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre Amsterdam, Amsterdam, Netherlands

Contact E-mail Address: e.grobbee@erasmusmc.nl

Introduction: Colorectal cancer (CRC) screening programs are implemented worldwide. Many are based on biennial fecal occult blood testing (FOBT). Despite well-known differences between men and women in incidence of CRC and its precursors, screening programs invariably use the same strategy for both genders. In recent years fecal immunochemical tests (FITs) replace guaiac FOBTs. The quantitative nature of FIT allows tailored screening by using different cutoffs. We aimed to evaluate whether different cutoffs should be used in men and women.

Aims & Methods: Participants (50-75 years) in an invitational primary colonoscopy screening program were asked to complete one sample FIT (OC-sensor, Eiken, Japan) before colonoscopy. We determined FIT positivity rates, sensitivity, specificity, detection rate and false-positivity rate in detecting advanced neoplasia (AN) for cutoff levels of 10 (FIT10), 20 (FIT20), 30 (FIT30) and 40 (FIT40) μg Hb/g feces in both men and women, corresponding to 25, 50, 75 and 100 ng Hb/ml feces. A receiver-operating-characteristic (ROC) curve was calculated for both men and women at multiple cutoffs to calculate the highest predictive ability.

Results: In total 1,256 invitees underwent FIT and colonoscopy, 638 men and 618 women, with a median age of 61 years (IQR 56-66) and 60 years (IQR 55-65). The prevalence of AN was 10.6% in men and 8.3% in women. At all FIT cut-offs, men had higher positivity rates than women. These ranged from 10.8% (95% CI 8.6-13.5%) to 3.8% (95% CI 2.5-5.6%) in men, and 8.4% (95% CI 6.5-10.9) to 3.2 (95% CI 2.1-5.0) in women. Sensitivity in men ranged from 40% (95% CI 29-52%) for FIT10 to 25% (95% CI 16-37%) for FIT40, and in women from 35% (95% CI 24-49%) for FIT10 to 22% (95%CI 12-35%) for FIT40. The highest predictive ability was similar for men and women with a maximum AUROC of 0.72, at different thresholds of 30 µg Hb/ml and 20 µg Hb/ml respectively. More advanced neoplasia was found and missed in absolute numbers in men for all cutoffs.

Conclusion: FIT-based CRC screening has a lower sensitivity and specificity for advanced neoplasia in women than in men. However, in absolute numbers more advanced neoplasia was both detected and missed in men compared to women at all cut-offs. When implementing a FIT-based CRC screening program these gender differences should be taken into account when aiming for optimal use of colonoscopy capacity.

Disclosure of Interest: None declared

P0393 HIGH PREVALENCE OF COLORECTAL CANCER IN PATIENTS WITH SERRATED POLYPOSIS SYNDROME: RETROSPECTIVE TWO-CENTER COHORT STUDY

E. J. Gómez¹, L. Pereyra¹, M. Omodeo¹, R. González¹, J. M. Mella¹, C. Fischer¹, G. N. Panigadi¹, M. L. González², N. Causada Calo², C. Vaccaro², J. A. De Paula², D. G. Cimmino¹, S. C. Pedreira¹, L. A. Boerr¹

¹Gastroenterology and Endoscopy Unit, Hospital Alemán, ²Gastroenterology, Hospital Italiano, Buenos Aires, Argentina

Contact E-mail Address: estanigomez@yahoo.com.ar

Introduction: Serrated polyposis syndrome (SPS) is characterized by the presence of multiple serrated polyps (SP) in the colon and may represent a risk for colorectal cancer (CRC). The SPS remains to be mostly unrecognized and not-well understood among other colorectal polyposis. The CRC prevalence and clinicopathological features of SPS are not well established.

Aims & Methods

Aim: To describe clinicopathological features of patients who meet WHO SPS diagnostic criteria and to determine prevalence and predictors of CRC.

Methods: We retrieved records from two teaching Hospitals to detect individuals with high diagnostic suspicion of SPS, between February 2002 and October 2014. Patients who met 2010 WHO SPS diagnostic criteria were included. Clinical and demographic data concerning age, gender, personal and familiar history of CRC, smoking status and surgical history were collected and analyzed. Continuous and categorical variables were reported as median with interquartile ranges (IQR), and percentages, respectively. Univariate analysis determining CRC predictors was performed. A P value < 0.05 was considered to be statistically significant.

Results: In all, 64 patients met WHO diagnostic criteria for SPS;: 33 (51%) fulfilled criteria 1, 29 (45%) criteria 2 and criteria 3 was observed in only 2 (3%) patients. Median age at diagnosis was 57.9 years (IQR, 25-80) and 42 (65%) were female. Nineteen (29.7%) had familiar history of CRC in first-degree relatives. Twenty nine (45%) had smoking history. A total of 220 colonoscopies were performed; an average of two per patient was necessary to confirm SPS diagnosis. Average endoscopic follow-up was 43.7 months. At index colonoscopy, 8 patients (12.5%) had between 5-10 polyps, 19 (29.7%) between 10-20 polyps, 25 (39%) between 20-30 polyps and 12 (18.7%) more than 30 polyps. A total of 659 SP were diagnosed by pathology reports; 193 (29.3%) were sessile serrated adenomas, 372 (56.5%) microvesicular hyperplastic polyps; 85 (12.8%) caliciform or unclassified hyperplastic polyps and 9 (1.4%) were traditional serrated adenomas. Forty-one patients (64%) had at least one conventional adenoma, 19 (29.7%) had at least one advanced adenoma and 32 (50%) had at least one advanced SP. CRC was found at diagnosis or during surveillance in 9 patients (14%). No clinicopathological predictors for CRC were identified in the univariate analysis. Surgery was performed in 12 (18.5%) patients due to polyposis (n=6), CRC (n= 4) and impossibility of SP endoscopic resection (n= 2).

Conclusion: In this two-center retrospective cohort study we found a high prevalence of CRC in SPS patients. However, we did not find clinical, endoscopic or pathological predictors for CRC. Our data suggests the need for a better detection and surveillance for CRC in SPS patients.

Disclosure of Interest: None declared

P0394 PREVALENCE OF ADVANCED COLORECTAL NEOPLASM IN LIVER TRANSPLANT RECIPIENTS

E. A. Kang¹, S. J. Koh², J. W. Kim², B. G. Kim², K. L. Lee², J. P. Im¹, J. S. Kim¹

¹Department of Internal Medicine, Seoul National University College of Medicine, ²Department of Internal Medicine, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea

Contact E-mail Address: cheerea@gmail.com

Introduction: Liver transplant patients are at high risk of malignancy because of the prolonged immunosuppression for avoiding rejections. The aim of this study was to determine whether the prevalence of advanced colorectal neoplasms increases in liver transplant recipients and to define the appropriate duration for surveillance colonoscopy after liver transplantation.

Aims & Methods: Our study consisted of 348 liver transplant patients who underwent a colonoscopy at Seoul National University Hospital from 1991 to 2012. For each patient, two or more age-and sex-matched controls were identified from a population of asymptomatic individuals.

Results: Eighteen (5.2%) patients had advanced colonic neoplasms, including colorectal cancers (10 patients, 2.9%), after liver transplantation. A case-control study showed that the odds of advanced colonic neoplasms occurring in transplant patients were 3.8 times greater than in the matched healthy controls. Transplant patients 50 years of age or older had a 4.1-fold higher risk of developing advanced neoplasm than did the matched subjects (OR 4.127; 95% CI 1.818-9.369; P=0.000).

Conclusion: Liver transplant patients are at an increasing risk of developing advanced colorectal neoplasms. Colonoscopy is recommended for patients before and after liver TPL, especially 50 years of age or older.

Disclosure of Interest: None declared

P0395 IMPACT OF SUBSEQUENT SCREENING EPISODES ON THE POSITIVE PREDICTIVE VALUE FOR ADVANCED NEOPLASIA AND ON THE DISTRIBUTION OF ANATOMIC SUBSITES OF COLORECTAL CANCER: A POPULATION-BASED STUDY ON BEHALF OF THE FRENCH COLORECTAL CANCER SCREENING PROGRAM

F. G. Assogba¹, D. Jezewski-Serra¹, D. Lastier¹, C. Quintin¹, B. Denis², N. Duport¹, N. Beltzer¹

¹Department of Chronic Diseases and Injuries, French Institute for Public Health Surveillance, Saint-Maurice, ²Association for Colorectal Cancer Screening, Colmar, France

Contact E-mail Address: f.assogba@invs.sante.fr

Introduction: The anatomic distribution of advanced colorectal neoplasia is increasingly important for choosing screening strategies and treatment options. We sought to evaluate the impact of repeated screening on the positive predictive value (PPV) for advanced colorectal neoplasia (advanced adenoma, AA, and colorectal cancer, CRC) and their distribution according to anatomic subsite distribution in average-risk adults.

Aims & Methods: The study included 98,031 men and women aged 50-74 who had a positive g-FOBT in 2010 and 2011 and underwent total colonoscopy. The PPV for detection of AA and CRC and the relative risks were determined with log-binomial models, and the distribution of anatomic subsites was estimated according to screening history.

Results: The median age was 61 years (62 years for participants with AA and 64 for those with CCR). The PPV for detection of advanced neoplasia was 24.5%, substantially higher in men than women (30.7% vs 17.7%), and it increased with age. It also fell at all screening episodes after the first. Subsequent screening episodes were associated with an increased RR for proximal AA (RR 1.13, 95%CI 1.16-1.20). Advancing age (RR 1.28, 95%CI 1.19-1.39 for every 10-year increase in age), female gender (RR 1.31, 95%CI 1.19-1.44), and subsequent screening (RR 1.15, 95%CI 1.04-1.27) were significantly and independently associated with detection of proximal adenocarcinoma. The latter was also detected at an advanced stage more often (RR, 1.24, 95%CI: 1.09-1.42). Early invasive adenocarcinoma (stages I and II) was more likely to be detected in a subsequent than an initial screening (RR 1.07, 95%CI 1.01- 1.13).

Conclusion: This study found that subsequent screening episodes using g-FOBT were associated with an increase in the detection rate of proximal AA and CCR, especially among women. The more frequent detection of CCR at an advanced stage in later screenings suggests that some of these tumors were present in earlier screenings. This potential for missed diagnoses on initial screening, together with the more modest increase in the rate of detection of invasive adenocarcinoma at early (and more curable) stages from the first to subsequent screenings, underlines the need to reinforce the population’s awareness of the importance of regular consistent screening, even after negative results.

Disclosure of Interest: None declared

P0396 CHARACTERIZING THE INTERPLAY BETWEEN THE WNT SIGNALING PATHWAY AND CD24 IN INTESTINAL TUMORIGENESIS

A. Fokra¹, S. Shapira¹, D. Kazanov¹, S. Kraus¹, N. Arber¹

¹Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

Contact E-mail Address: afokra@gmail.com

Introduction: CD24 is a glycosylphosphatidylinositol-linked protein that functions as an adhesion molecule and is overexpressed at an early stage of CRC (Sagiv et al., 2006). The Wnt/b-catenin signaling pathway plays an important role in CRC carcinogenesis process. A previous publication from our lab indicated that CD24 could affect the tumorigenesis process in Apc^Min mice (Naumov et al., 2014); Apc^Min mice usually develop anemia (polyp bleeding) and splenomegaly (extra-medulary hematopoiesis).

Aims & Methods: CD24's role might be, partly, through direct interaction/s with components of the Wnt pathway. Apc^Min and CD24 knockout (KO) mice, both on a C57BL/6J genetic background, were crossed to generate double KO transgenic mice. Genotypes were routinely verified by analysis of DNA extracted from tail biopsies. Small and large bowel polyps were counted macroscopically following methylene blue staining and histology was verified microscopically. Colonic polyps were measured and counted using mice colonoscopy. CD24-inducible 293T-Rex cells previously developed in our lab (Shapira et al., 2011) and SW480 CRC cells stably transfected with CD24 (Naumov et al., 2014) were used to study this interaction in vitro.

Results: In vitro Western blotting analyses showed that expression of CD24 in 293T-Rex cells induced the activation of β-catenin, while down-regulation of CD24 in SW480 cells caused a decrease in the levels of active β-catenin. Depletion of CD24 alleles in Apc^Min mice led to a significant reduction in the number of polyps in the small and large intestine. C57BL6/J mice carrying the Apc^Min mutation develop ∼24.3 ± 3.7 adenomas and several carcinomas in the small intestine by the age of 16 weeks. The Apc^Min/CD24^+/- mice developed 8 ± 1.4 polyps and Apc^Min/CD24^-/- (double KO) mice developed ∼7 ± 1.7 polyps (p=0.006). Colonoscopy shows a significant reduction in the number and size of polyps upon depletion of CD24 alleles. In the current study the Apc^Min displayed severe splenomegaly (355 ± 68 mg) compared to (205 ± 51 mg) in Apc^Min/CD24^+/- mice and (141 ± 49 mg) in double KO mice similar to WT mice (p=0.006). Hb level was 3.8 ± 2.5 in the Apc^Min significantly lower in the double KO mice (8.2 ± 0.9) and the WT (p=0.0009)

Conclusion: CD24 plays a major role in intestinal tumorigenesis. Knocking down even one copy of CD24 almost completely abolished formation in vivo, and prevent anemia and splenomegaly the whole mark of intestinal blood loss seeing in the Apc^Min. CD24 interacts with the Wnt pathway by activating β-catenin. 4. Down regulation of CD24 maybe an important aim in the therapy of CRC.

Disclosure of Interest: None declared

P0397 IDENTIFICATION OF LONG NON-CODING RNAS (LNCRNA) WITH ALTERED EXPRESSION LEVELS IN COLORECTAL ADENOMA AND CARCINOMA

A. Kalmár¹, Z. B. Nagy¹, O. Galamb¹², B. Wichmann¹², B. K. Barták¹, K. Tóth¹, P. Miheller¹, Z. Tulassay¹², B. Molnár¹²

¹2nd Department of Internal Medicine, Semmelweis University, ²Molecular Medicine Research Unit, Hungarian Academy of Sciences, Budapest, Hungary

Contact E-mail Address: alexandra.kalmar@gmail.com

Introduction: Among several functions long non-coding RNAs (lncRNA) are known to act as crucial epigenetic regulators of cell proliferation. Their expression level alterations can lead to cancer formation. Identification of lncRNA expression profiles in colorectal adenoma and cancer (CRC) would be beneficial to expand our knowledge of CRC development.

Aims & Methods: This study aimed to identify differentially expressed long non-coding RNAs (lncRNA) in colorectal adenoma and CRC cases. Total RNA was isolated from 94 human colonic biopsy samples (27 CRCs, 29 colonic adenomas, 38 normal donors without evidence of disease) with RNeasy Mini Kit (Qiagen). Expression levels of lncRNAs were analyzed with HGU133Plus2.0 microarrays (Affymetrix). Affymetric probe sets of 2090 lncRNAs already represented on this array type were extracted with non-coding (,NR”) Refseq IDs. Furthermore, total RNA including miRNAs was isolated from 36 independent biopsy samples (20 CRCs, 9 colonic adenomas, 7 normal donors without evidence of disease) with High Pure miRNA Isolation Kit (Roche) and expression levels of 40.914 non-protein coding transcripts were analyzed by using Human Transcriptome Array 2.0 (Affymetrix). Data were analysed using Expression Console and Transcriptome Analysis Console softwares (Affymetrix).

Results: According to HGU133Plus2.0 microarray results 3 significantly upregulated lncRNAs were identified in adenomas and 4 in CRCs, while 10 significantly downregulated lncRNAs were found in adenomas and 12 in CRC compared to the healthy controls (p < 0.05; -1 ≥ logFc ≥ 1). On the basis of the Human Transcriptome array results -analyzing broader range of non-coding RNAs- 76 upregulated lncRNAs were detected in adenomas and 154 in CRC, while 65 downregulated lncRNAs were found in adenomas and 122 in CRC compared to the healthy controls (p < 0.05; -2 ≥ logFc ≥ 2). 100% of the lncRNAs showing significant gene expression alteration on HGU133Plus2.0 arrays showed similar expression alteration tendency on Human Transcriptome arrays in the adenoma vs. normal and 94% in the CRC vs. normal comparisons. Interestingly, on HGU133Plus2.0 arrays 69% and on Human Transcriptome Arrays 73% of lncRNAs upregulated in CRC samples showed significantly elevated expression (p < 0.05) already in adenoma samples (e.g. upregulated CRNDE, linc-FAM75A7-18, linc-FAM135A, lincDUSP26-1 and downregulated linc-DCLK3-2, linc-AMN1, linc-SOD3-2, lincFAM55D compared to healthy controls) containing lncRNAs already associated with CRC or other types of cancer.

Conclusion: The identified lncRNAs with significantly altered expression levels can play a central role in the regulation of transcription during colorectal adenoma-carcinoma sequence. Common up- or downregulated lncRNAs in colorectal adenoma and in CRC samples can be the basis of further investigations in order to enhance early detection of the colorectal cancer development.

This study was supported by the National Research, Development and Innovation Office (KMR-12-1-2012-0216 grant).

Disclosure of Interest: None declared

P0398 NOVEL THERAPEUTIC STRATEGY FOR MICRORNA DELIVERY TO COLON CANCER CELLS – A CETUXIMAB-BASED APPROACH

A. Simões¹, A. C. Santos¹, S. Gomes¹, D. Pereira¹, J. Gonçalves¹, C. Rodrigues¹, P. Borralho¹

¹Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal, Lisbon, Portugal

Contact E-mail Address: asimoes@ff.ulisboa.pt

Introduction: The discovery of the deregulation of microRNA (miRNA) expression in cancer, particularly in colon cancer has demonstrated the potential therapeutic use of miRNAs. However, the biggest obstacle relies in the low miRNA delivery efficiency in vivo.

Aims & Methods: In this study, we aimed to develop an efficient strategy for the delivery of miRNAs to colon cancer cells. Cetuximab was used as a delivery and targeting agent.

Cetuximab was FITC-labeled using FluoReporter® FITC Protein Labeling Kit, providing a labeling ratio of ∼ 11 (FITC:Cetuximab). Subsequently, we linked anti-FITC-Protamine single chain Fv (scFv) antibody conjugate to the FITC-labeled Cetuximab. Further, miRNAs were loaded onto Protamine moieties, which display high affinity for nucleic acids and have already been demonstrated effective in in vitro and in vivo delivery of siRNAs to cancer cells. We have tested the effectiveness and specificity of our delivery complex through in vitro evaluation of increased levels of miRNA payload in target cells.

Results: Immunofluorescence and flow cytometry results showed that Cetuximab-FITC efficiently binds to HCT116 cells, but not SW620 cells that do not express EGFR. For Cetuximab-FITC above 0.5 nM, all HCT116 cells were FITC-positive, whereas all SW620 cells were FITC-negative, as evaluated by FACS (p < 0.05). Further, for Cetuximab-FITC up to 50 nM, only 3% of SW620 cells were FITC-positive, demonstrating the specificity of EGFR targeting by Cetuximab-FITC. Subsequently, we confirmed by ELISA the specific binding of anti-FITC-protamine to Cetuximab-FITC (p < 0.01). The concentration of 3 nM Cetuximab-FITC was selected to evaluate the delivery of anti-FITC-protamine scFv at 10:1 ratio (scFV:cetuximab-FITC), and the results show specific delivery to HCT116 cells as evaluated by Western blot. Finally, we confirmed by flow cytometry and RT-PCR the increase and specific delivery of miRNAs into colon cancer cells with the developed delivery tool consisting of cetuximab-FITC:scFV:miRNA (p < 0.05).

Conclusion: The great enthusiastic advantage of the development of this delivery tool arises from the combination of the therapeutic agent Cetuximab already in use for colon cancer treatment together with RNA interference technology. The results obtained thus far illustrate the high potential for efficient and specific delivery of miRNAs to cancer cells, and may provide additional and novel therapeutic tools to expand current options in colon cancer management.

(Supported by PTDC/SAU-ORG/119842/2010, and SFRH/BD/79356/2011 from FCT).

Disclosure of Interest: None declared

P0399 GUT MUCOSAL MICROBIOME ACROSS STAGES OF COLORECTAL CARCINOGENESIS

G. Nakatsu¹, X. Li¹, H. Zhou², S. H. Wong¹, W. K. Wu¹, S. C. Ng¹, H. Tsoi¹, Y. Dong¹, J. J. Sung¹, J. Yu¹

¹Institute of Digestive Disease and Department of Medicine and Therapeutics, ²Department of Microbiology, The Chinese University of Hong Kong, Hong Kong, Hong Kong

Contact E-mail Address: junyu@cuhk.edu.hk

Introduction: Sustained gut microbial dysbiosis is a potential risk factor for exacerbating colorectal lesions toward carcinogenesis. However, it remains unclear whether specific members or a consortium of the gut microbes has the potential to explicate observations about tumor progression.

Aims & Methods: To catalogue the taxonomic landscape of microbial communities in colorectal carcinogenesis, we performed 16S rRNA gene sequencing on mucosal biopsies from 61 lesion-free individuals, and on paired biopsies from 47 and 52 individuals with histology-proven adenomas and carcinomas, respectively. Using the DMM models, we partitioned the relative abundance profiles into microbial community types to design tumor-stage analysis of the changes in community types and marker taxa between paired samples. The taxon abundances were also subjected to sparsity-corrected correlation analyses of occurrence relationships using the SparCC algorithm. Finally, we imputed the metagenomic content of mucosal community types associated with the disease-states using the PICRUSt algorithm and HUMAnN pipeline.

Results: We detected five robust community types, which were strongly associated with phenotypes of the colorectal mucosae (P = 0.00007). A community type predominated by the potentially pathogenic members of oral microbiome was primarily associated with carcinomas, whereas adenomas were assigned to a community type with high intra-cluster variabilities. Normal control mucosae were more likely to be represented by a community type enriched with members of Clostridia. We confirmed the consistent enrichments of representative taxa by real-time PCR amplification on an independent cohort of comparable size. Disease-stage analysis revealed significant patterns of change in community types at cancerous but not adenomatous sites relative to their adjacent normals. The fold changes of marker taxa were most significant in early-stage CRC. Colorectal niches of cancer- and cancer-adjacents were characterized by a markedly increased number of parasitic relationships. Adenoma-adjacents harboured co-excluding partners underlying early signs of mucosal dysbiosis. By contrast, microbial partners in normal mucosae showed strong mutualistic relationships. Furthermore, both pathological phenotypes of mucosa and the community types strongly distinguished the predicted metabolic potentials of mucosal communities.

Conclusion: Pathogenesis of CRC can be linked to the appearances of pathobiont-like microbial consortia in which protagonists interact with one another. Such polymicrobial signature predicts the statuses of colorectal lesion, the progression of which may be dependent on the processes of microbial community assembly at the mucosal interface. By interrogating the mucosal community ecology across disease-states, we gain deeper understanding of etiological factors in colorectal carcinogenesis by considering complex bacterial driver-passenger interactions.

Disclosure of Interest: None declared

P0400 ASSOCIATION OF COLORECTAL CANCER WITH PATHOGENIC ESCHERICHIA COLI: FOCUS ON MECHANISM USING OPTICAL IMAGING

J. Veziant¹, V. Bonnin¹, E. Jouberton², J. Gagnière¹³, P. Sauvanet¹, D. Pezet³, N. Barnich¹, E. Miot-Noirault², M. Bonnet¹

¹M2iSH, UMR1071 Inserm/Université d'Auvergne, ²IMTV, UMR990 Inserm/Université d'Auvergne, ³Digestive Surgery, CHU Clermont Ferrand, Clermont Ferrand, France

Contact E-mail Address: julieveziant@gmail.com

Introduction: Colorectal carcinoma (CRC) is a complex association of non neoplastic and tumoral cells and a large amount of microorganisms. E. coli is a consistent commensal of the human gut microbiota but some pathogenic strains have acquired the ability to produce toxins as cyclomodulins that can interfere with eukaryotic cell cycle or directly induce DNA damages. It was observed that cyclomudulin-producing-E. coli are more frequently detected on CRC patients and exhibit procarcinogenic properties on murine models (HCT116 xenograft, AOM/DSS; APCmin/+).

Aims & Methods: Aim of this study was to investigate some molecular or cellular mechanisms related to the infection of epithelial mucosa by cyclomudulin-producing-E. coli using optical in vivo imaging (IVIS spectrum; Perkin Elmer). In vivo imaging is an innovative tool for noninvasive, spatiotemporal and quantitative monitoring of carcinogenesis process in mice models. We choose to evaluate the tumor metabolic activity using a FDG analogue as 2-DG-750 fluorescent probes and inflammation measuring myeloperoxidase (MPO) activity with a bioluminescent inflammation probe. This detection is dependent on reactive oxygen species (ROS) production. Detection and quantitation of these two signals were validated on a xenograft model of human colon adenocarcinoma epithelial cells (HCT-116) in nude mice infected with a cyclomudulin-producing-E. coli (11G5) and then tested on the murine CRC susceptibility model, APC^min/+.

Results: Using the 2-DG-750 probe, we observed a high and specific HCT-116 tumor uptake in correlation with tumoral volume (Pearson correlation factor: 0.9181 p < 0.05). Using inflammation probe, we detected a rapid systemic elimination and a strong signal in the HCT116 tumor of the 11G5 infected group 10 minutes post-probe-injection. Quantitation showed a significant increase (+ 1288%) of luminescent signal in the tumors of the infected group (p < 0.05). We confirmed this by enzyme-linked immunosorbent assay (ELISA) on tumor specimens. MPO levels (ng/ml) was significantly higher (1556 ± 313.6 vs 234.6 ± 121.6 p=0.001) in xenograft infected with pathogenic E.coli-11G5 strain. Moreover histological examination of tumor samples confirmed the massive infiltration of HCT116-11G5 infected xenograft by neutrophils as compared to uninfected group. These data validated used of inflammation probe and showed that E.coli strain infection induced inflammation and ROS production in the tumor. Study of intra-digestive signal on the murine APC^min/+ models is in progress. Strong signals were co-localized with polyps.

Conclusion: Novel imaging techniques like optical imaging could be a powerful tool in translational cancer research. Bioluminescent approach can be applied to digestive tumor and seems sensitive to noninvasively monitor longitudinal tumor inflammation and oxidative stress using a commercial probe. Here we showed that E.coli infection induce inflammation and oxidative stress which could participate on carcinogenesis process. In vivo imaging could be an effective technology to better understood host-pathogen interactions on tumoral development.

Disclosure of Interest: None declared

P0401 EXTRACELLULAR GALECTIN-3 ENHANCES COLON CANCER CELLS MIGRATION AND INVASION RELATED TO DYNAMIC CHANGES OF EPITHELIAL GROWTH FACTOR RECEPTOR

K.-L. Wu¹, E.-Y. Huang², C.-C. Hsiao³, K. D. Yang⁴

¹Division of Hepatogastroenterology, ²Division of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, ³Graduate Institute of Clinical Medical Sciences, Chang Gung University, ⁴Department of Medical Research and Development, Show Chwan Memorial Hospital at Chang Bing, Changhua, Kaohsiung, Taiwan, Province of China

Contact E-mail Address: kengliang_wu@yahoo.com.tw

Introduction: Our previous study showed galectin-3 enhanced the migration of DLD-1 cells through K-Ras-Raf-Erk1/2 pathway, but extracellular galectin-3 on the migration of cancer cells and interaction with epithelial growth factor receptor (EGFR) remained unknown.

Aims & Methods: To clarify the effect of extracellular galectin-3 on the migration and invasion of colon cancer cells and relation with EGFR. Western blotting was used to analysis the secretion of galectin-3, short hairpin ribonucleic acid to stably knockdown the expression of galectin-3, wound healing and trans-well assays to evaluate the migration and invasion of colon cancer cells and immunoprecipitation /immunoblotting and proximity ligation assays for analyzing the interaction between galectin-3 and EGFR.

Results: Caco2 cells secreted more galectin-3 and migrated faster than DLD-1. The migration was inhibited by lactose and neutralizing anti-galectin-3 antibody. DLD-1 cells with knockdown of galectin-3 decreased the migration but restored by recombinant galectin-3. Blocking EGFR by EGFR antibody caused decrease of migration. DLD-1 cells with knockdown of galectin-3 decreased the invasion but recombinant galectin-3 reversed the decrease. An interaction between EGFR and galectin-3 was proven by immunoprecipitation and proximity ligation assays. Addition of recombinant galectin-3 induced an increase in phosphorylated EGFR expression within minutes, and recombinant galectin-3 enhanced entrance of EGFR from cell membrane to cytoplasma, especially under EGF stimulation. Extracellular galectin-3 increased the migration and invasion of colon cancer cells and that was correlated to its interaction with EGFR and internalization of EGFR from cell membrane to cytoplasm.

Conclusion: Targeting galectin-3 might have a synergistic effect on the EGFR targeting therapy.

Disclosure of Interest: None declared

P0403 DETECTION OF COLORECTAL CANCER AND ADVANCED ADENOMAS FOLOWING GFOBT TEST 5-6 YEARS AFTER NORMAL COLONOSCOPY IN COMPARISON TO GFOBT TEST ON THE THIRD AND FOURTH SCREENING ROUND

A. Kaufmanis¹, C. Exbrayat², J. Brousse-Potocki³, K. Haguenoer⁴

¹ADC77, Lieusaint, ²ODLC, Meylan, ³ADECAM56, Vannes, ⁴CCDC CHRU, Tours, France

Contact E-mail Address: a.kaufmanis@adc77.org

Introduction: The French colorectal cancer (CCR) screening program was generalized in 2008 and is based on a biennial fecal occult blood testing (FOBT) proposed to everyone with an average risk for colorectal cancer and aged 50-74 years. Subjects from this population who undergo a normal colonoscopy are invited 5 years later for a biennial FOBT. Our data base contains information about FOBTs performed five years after colonoscopy as well as about several rounds of FOBTs. The test in use till 2015 was guaiac FOBT (gFOBT), Hemoccult II®.

Aims & Methods: Our primary aim was to compare CCR and advanced adenoma (AA) detection rates following gFOBT 5-6 years after normal colonoscopy with those observed on third and fourth rounds of screening with gFOBT. We evaluated data from 46 French districts. The study population was those aged 55-74 years and eligible for screening who had performed a gFOBT from 2008 to 2013 and qualified for one of three groups: subjects with gFOBT preceded by normal colonoscopy (COLO), subjects with gFOBT preceded by two negative gFOBTs (R3) and subjects with gFOBT preceded by three negative gFOBTs (R4). The last group had data from only 11 districts where screening existed for long enough. In R3 and R4, the intervals between all consecutive tests had to be 18-36 months. The interval between colonoscopy and gFOBT had to be 5-6 years.

Results: In total, 38 587 men and 56 957 women were included in the COLO group, 370 975 men and 469 082 women in R3 and 101 994 men and 115 090 women in R4. CCR detection rates for men were 0.7‰ in COLO, 2.0‰ in R3 and 1.6‰ in R4; it was 0.4‰, 0.9‰ and 0.8‰ respectively for women. Among men, AA detection rates were 3.2‰ in COLO, 5.9‰ in R3 and 5.8‰ in R4; it was 1.7‰, 2.6‰ and 2.3‰ respectively for women. Among men, the relative risk (RR) to detect CCR in COLO compared to R3 was 0.36 (95% Confidence Interval (95%CI) 0.25-0.52); it was 0.44 (95%CI 0.30-0.66) compared to R4. Among women, the COLO to R3 RR was 0.40 (95%CI 0.26-0.61) and the COLO to R4 RR was 0.45 (95%CI 0.28-0.72). Among men, the RR to detect AA in COLO compared to R3 was 0.55 (95%CI 0.49-0.66); it was 0.56 (95%CI 0.46-0.68) compared to R4. Among women, the COLO to R3 RR was 0.65 (95%CI 0.53-0.79) and the COLO to R4 RR was 0.74 (95%CI 0.59-0.93).

Conclusion: The risks to discover CCR or AA were lower within the group of the subjects who performed gFOBT five-six years after normal colonoscopy in comparison to those who performed a gFOBT after two or three negative gFOBTs. The observed difference was larger for CCR than AA. While French colorectal cancer screening program is changing with replacement of the guaiac based test by more sensitive fecal immunochemical test (FIT), these results support this evolution. Further analysis would be of great benefit to evaluate how several rounds of screening with high-sensitivity FIT compares to single colonoscopy and what is the number of screening rounds needed to equal colonoscopy. In France the five-year period to reintegrate into screening program subjects with a normal colonoscopy could be discussed and compared to a 10-year interval.

Disclosure of Interest: None declared

P0404 INTRA-TUMORAL (ITB) AND PERI-TUMORAL BUDDING (PTB): PREDICTORS OF TUMOR PROGRESSION, LYMPH NODE AND DISTANT METASTASES IN COLORECTAL CANCER

A. Lugli¹, G. Rieger¹, V. Koelzer¹, H. Dawson¹, L. Sokol¹, M. Berger², M. Haedrich³, B. Schnueriger³, D. Inderbitzin⁴, I. Zlobec¹

¹University of Bern, Institute of Pathology, ²Department of Medical Oncology, ³Departments of Visceral Surgery and Medicine, University Hospital Bern, ⁴Department of Surgery, Tiefenau Hospital, Bern, Switzerland

Contact E-mail Address: alessandro.lugli@pathology.unibe.ch

Introduction: Tumor budding in colorectal cancer (CRC) is a strong, reproducible and independent prognostic factor. Whereas intra-tumoral budding (ITB) is defined as single tumor cells or a small cluster of up to 5 cells found in the tumor center, peri-tumoral budding (PTB) can be detected at the invasion front of CRC. Until now, a comparison of the clinicopathological impact of ITB and PTB by tumor region has not been performed.

Aims & Methods: The aim of the study was to validate the performance of tumor budding as a marker of tumor progression in all CRC stages independently of the cancer region.

Postoperative resections of 156 surgically treated and well-characterized stage I-IV CRC patients were systematically reviewed according to the latest UICC/AJCC classification. Collected information included patient age, gender, tumor location, TNM stage, L and V stage, tumor grade, histological subtype, perineuronal infiltration, tumor border configuration, mismatch repair status, R classification and information on adjuvant therapy. Tumor budding was optimally visualized by immunohistochemistry using pancytokeratin, a well-established marker in daily diagnostics. ITB was scored using the 1 high-power field (HPF) method to simulate the clinical scenarios in pre-operative biopsies and malignant polyps. A cut-off score of 5 buds/HPF based on Receiver Operating Characteristic (ROC) curves was used to distinguish between high and low-grade budding. Next, PTB was assessed using the 10 HPF method and the ROC based cutoff of 100 buds was identified for categorizing high and low-grade budding in postoperative CRC resections.

Results: ITB (1 HPF) and PTB (10 HPF) were strongly correlated (r=0.82, p < 0.0001). PTB was associated with T stage (p=0.02), N stage (p=0.04), TNM stage (p=0.04) and tumor grade (p=0.02), whereas ITB significantly correlated with higher T stage (p < 0.01), N stage (p=0.03), distant metastases (p=0.02), L stage (p < 0.01), V stage (p=0.03) and tumor border configuration (p < 0.01). Combined ITB and PTB scores independently correlated with poor survival outcome (HR (95%CI): 1.02, CI: 1.0002-1.04, p=0.03) when adjusted for TNM-stage and adjuvant therapy.

Conclusion: Tumor budding is a strong adverse prognostic parameter independent of the cancer region (center vs front). The 10HPF/1HPF tumor budding scoring method can be applied in all CRC stages, which may be applicable to clinical scenarios including preoperative biopsies, malignant polyps and stage II CRC.

Disclosure of Interest: None declared

P0405 SERRATED ADENOMA MODEL OF THE COLON

M. Y. Byakhov¹, D. L. Rotin¹, A. E. Lychkova²

¹Moscow Clinical Scientific Center, Moscow, Russian Federation, ²patent department, Moscow Clinical Scientific Center, Moscow, Russian Federation

Contact E-mail Address: lychkova@mail.ru

Introduction: Serrated adenoma is a distinct type of lesion of the colon, with potential to evolve into colorectal cancer through a different molecular pathway than the traditional adenoma-carcinoma sequence.

Aims & Methods: Establish a possibility of creating a model of colon serrated adenoma.

Proposed a novel rat model for SA caused by picrilsulfonic acid administration. 6 Wistar rats weighing 220-250 g received picrilsulfonic acid administrated into the lumen of the common bile duct in a dose of 0.03-0.05 ml, and readministrated 5-10 days after in the same dose. The control group consisted of 5 rats. A sample of colon after 3-4 months under anesthesia was taken. Histopathological examination of the tissues stained with hematoxylin and eosin was carried out.

Results: Histologically the cecum contain polypoid formations extending out of the mucous surface; dilated crypts were presented, glands with irregular outlines parallel to a broad base of muscularis mucosa were located. Crypts were lined by epithelial cells with small nuclei and light eosinophilic cytoplasm, sometimes with mild dysplasia; crypts not contained endocrine cells. The combination aserrated crypts and surface epithelial dysplasia revealed the presence of serrated adenoma.

Conclusion: Proposed model explicitly includes morphological signs of a serrated adenoma and may be used in potential screening strategies for colorectal cancer.

Disclosure of Interest: None declared

P0406 CLINICAL IMPLICATION OF AXIN-2 EXPRESSION IN COLORECTAL CANCER

G. Veloudis¹, A. Pappas², C. Liatsos³, D. Keramidaris¹, E. Falidas¹, E. Pikoulis⁴, J. Bramis⁴, E. Bastounis⁴

¹First Surgical Department, 417 NIMTS Military Veterans’ Fund Hospital, ²Department of Gastroenterology., Sismanoglio General Hospital, ³Endoscopy department, 401 General Army Hospital, ⁴First Surgical Department, Laikon University Hospital, Athens, Greece

Contact E-mail Address: apopapp300@yahoo.com

Introduction: The Wnt pathway regulates cellular homeostasis and deregulation of this pathway has been implicated in the pathogenesis of many diseases including colorectal (CRC) cancer. The Axin-2 protein plays an important role in the regulation of the stability of the Wnt signaling pathway. Although initially described as a tumor suppressor, recent findings support the presence of a pro-tumorigenic role.

Aims & Methods: The aim of this study is to investigate the association of Axin-2 mRNA and protein expression with clinicopathological parameters and survival in CRC. Fifty seven patients who were diagnosed with adenocarcinoma of the colon and rectum and underwent resection at our surgical department were included in this study. Expression of Axin-2 was investigated using quantitative PCR and immunohistochemical staining.

Results: In most cases Axin-2 immunolocalization was detectable in the cytoplasm as opposed to only one case where it was shown to be expressed in the nucleous. The positive expression rates of Axin-2 mRNA and protein were 51% (29/57) and 33% (19/57), respectively. Statistical analysis showed no association between Axin-2 mRNA/protein expression and patients’ clinicopathological parameters and survival.

Conclusion: In the present study Axin-2 mRNA and protein expression failed to provide with significant prognostic information in CRC patients. These findings may reflect the complex tumorigenic role of this marker in CRC. Further studies are required to verify our results.

Disclosure of Interest: None declared

P0407 CLINICAL SIGNIFICANCE OF E-CADHERIN IN COLORECTAL ADENOCARCINOMAS

A. Pappas¹, G. Veloudis², C. Liatsos³, S. Gourgiotis², D. Keramidaris², E. Pikoulis⁴, J. Bramis⁴, E. Bastounis⁴

¹Department of Gastroenterology, Sismanoglio General Hospital, ²First Surgical Department, 417 NIMTS Military Veterans’ Fund Hospital, ³Endoscopy department, 401 General Army Hospital, ⁴First Surgical Department, Laikon University Hospital, Athens, Greece

Contact E-mail Address: apopapp300@yahoo.com

Introduction: The epithelial–mesenchymal transition (EMT) represents a fundamentally important process during the embryonic development, but it is also recognized as a critical event in the progression and metastases of many epithelial tumors. E-cadherin is the best-characterized molecular marker of EMT and loss of expression has been linked to poorer prognosis in several cancers. To date, in patients with colorectal cancer (CRC), the correlation between E-cadherin and patient prognosis remains controversial.

Aims & Methods: The aim of this study was to investigate E-cadherin mRNA/protein expression in a series of 57 CRC patients and relate these findings with the patients’ clinicopathological features and prognosis. Quantitative PCR and immunohistochemistry analyses were performed to characterize the expression of E-cadherin in CRC tissues.

Results: The positive expression rates of E-cadherin mRNA and protein were 53% (30/57) and 42% (24/57), respectively. E-cadherin immunostaining showed no correlation with the patients’ clinicopathological features. There was a trend towards higher mRNA expression levels in patients with well compared to poorly differentiated tumors (p=0.09). Kaplan-Meier survival curves demonstrated that patients with negative E-cadherin mRNA and protein expression, presented a significantly and marginally significantly unfavorable disease-free survival (DFS) time (p < 0.001 and p = 0.05, respectively). Patients with negative E-cadherin mRNA expression presented also a significantly unfavorable overall survival (OS) time (p = 0.02). Multivariable COX regression analysis adjusted for age, gender, tumor location, TNM stage and grade of differentiation, showed that E-cadherin mRNA expression is an independent prognostic factor for OS.

Conclusion: E-cadherin downregulation is an important component of disease progression in CRC patients. Gene expression levels are a strong predictor of OS and DFS.

Disclosure of Interest: None declared

P0408 EXPRESSION AND LOCALIZATION OF β-CATENIN IN COLORECTAL CANCER

G. Veloudis¹, A. Pappas², C. Liatsos³, S. Gourgiotis¹, V. Komborozos⁴, E. Pikoulis⁵, J. Bramis⁵, E. Bastounis⁵

¹First Surgical Department, 417 NIMTS Military Veterans’ Fund Hospital, ²Department of Gastroenterology, Sismanoglio General Hospital, ³Endoscopy department, 401 General Army Hospital, ⁴Third Surgical Department, Evangelismos Hospital, ⁵First Surgical Department, Laikon University Hospital, Athens, Greece

Contact E-mail Address: apopapp300@yahoo.com

Introduction: Aberrant activation of the Wnt signaling pathway has been implicated as a key regulator of colorectal (CRC) tumorigenesis. β-catenin plays a key role in the signaling output of the Wnt cascade. There are many reports about the significance of β-catenin in CRC, yet correlations with prognosis remain highly variable and contradictory.

Aims & Methods: The aim of this study was to investigate β-catenin expression and its relationship to clinicopathological parameters and prognosis in CRC. Immunohistochemistry analyses were performed to characterize the expression of β-catenin in CRC tissues.

Results: The study included 29 female and 28 male patients with a mean age of 67 ± 10.4 years. Cytoplasmic and focal nuclear accumulation of β-catenin was observed in 88% (50/57) and 25% (14/57) of patients respectively. There was no significant association between β-catenin overexpression in the cytoplasm and the patients’ clinicopathological parameters. β-catenin overexpression in the nucleus was associated with advanced N stage (p=0.04). Kaplan-Meier survival curves demonstrated that patients with β-catenin overexpression in the nucleus presented a significantly unfavorable overall survival (OS) time (p=0.04). Multivariable COX regression analysis adjusted for age, gender, tumor location, TNM stage and grade of differentiation, showed that β-catenin overexpression in the nucleus is an independent prognostic factor for OS. There was no significant association between β-catenin overexpression in the cytoplasm and OS.

Conclusion: The protein expression level of nucleus, rather than cytoplasmic β-catenin predicts CRC patients with worse prognosis.

Disclosure of Interest: None declared

P0409 WHICH CRITERIA TO USE TO DIFFERENTIATE BETWEEN SESSILE SERRATED ADENOMA (SSA) FROM MICROVESICULAR HYPERPLASTIC POLYPS – A 5-YEAR RETROSPECTIVE HISTOPATHOLOGICAL STUDY

C. Sumánszki¹, R. Horváth¹, T. Micsik², Z. Tulassay¹, A. V. Patai¹

¹2nd Department of Internal Medicine, ²1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary

Contact E-mail Address: arpad.patai@gmail.com

Introduction: During the past two decades sessile serrated adenomas (SSA) received considerable attention due to their increased risk of leading to colorectal carcinoma (CRC). CRCs arising from SSA have frequently been associated with interval cancers (those arising after negative colonoscopy). Diagnosis of these lesions can be challenging, as both macroscopic and microscopic features show similarities to microvesicular hyperplastic polyps (MVHP). Since in contrast to SSA, there is almost no malignant potential of MVHP, therefore it is critical to distinguish them from SSA in order to determine the appropriate follow up and prevent interval cancers.

Aims & Methods: The aims of our study were to compare the published histopathological classification criteria currently available in the literature for the diagnosis of SSAs and to use these criteria to examine the reclassification rate of MVHP to SSA. Colorectal polyps diagnosed between 2010 and 2014 at the 1st Department of Pathology and Experimental Cancer Research were searched for samples with descriptions matching serrated lesions. For the diagnosis of SSAs the criteria recommended by Rex et al. were used. The remaining serrated lesions were classified using the WHO 2010 criteria. These lesions were then reanalysed using seven major histopathological classification studies (Aust 2010, Chung 2008, Higuchi 2005, Mohammadi 2011, Rex 2012, WHO 2010, Yao 2011) and reassessed whether they met the diagnostic criteria for the diagnosis of SSA.

Results: A total of 347 serrated colonic polyps were found that included 50 (14.4%) SSAs, 143 (41.2%) MVHPs, 148 (42.7%) goblet cell rich hyperplastic polyps (GCHP) and 6 (1.7%) traditional serrated adenomas (TSAs). A significant difference for SSA diagnosis was noted between the classification studies, with results varying from 100% (Rex 2012, Higuchi 2005, Mohammadi 2011) to 20% (Chung 2008). This difference was also observed in the reclassification rate of MVHP to SSA: ranging from 15 (10.5%) (Rex 2012) to 2 (1.4%) (Chung 2008) of all MVHPs.

Conclusion: In conclusion, we would like to emphasize the significant difference among studies differentiating colorectal serrated lesions. It seems to be clear that a universal diagnostic criteria based on prospective clinicopathological studies is needed to avoid the underdiagnosis that can result in inadequate surveillance and increased risk of CRC.

Disclosure of Interest: None declared

P0410 WHICH CRITERIA TO USE TO DIAGNOSE TRADITIONAL SERRATED ADENOMA (TSA) AND DIFFERENTIATE FROM CONVENTIONAL ADENOMA – RESULTS FROM A 3-YEAR RETROSPECTIVE HISTOPATHOLOGICAL STUDY

R. Horváth¹, C. Sumánszki¹, T. Micsik², L. Vass³, I. Horváth³, E. Román³, B. Nagy⁴, Z. Tulassay¹, A. V. Patai¹

¹2nd Department of Medicine, ²1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, ³MD Ltd, ⁴4th Department of Medicine and Gastroenterology, Flór Ferenc Hospital of Pest County, Kistarcsa, Hungary

Contact E-mail Address: arpad.patai@gmail.com

Introduction: Among the recently described colorectal serrated lesions traditional serrated adenoma (TSA) is the rarest subtype. The morphologic distinction between TSA and conventional adenoma, especially villous/tubulovillous adenoma (VA/TVA), may be difficult, because there is a significant histological overlap between these lesions. According to the literature, there are three characteristic features usually present in TSAs: ectopic crypt foci (ECF), luminal serration and typical cytology with columnar epithelial cells with eosinophilic cytoplasm and elongated, centrally placed nuclei. Currently, TSA diagnosis needs at least two of the three features above with at least one present in 50% of the polyp.

Aims & Methods: The aim of our study was to evaluate the presence of these morphological features in TSAs and TVAs, and define which features are most helpful in distinguishing TSA from TVA. Colorectal polyps diagnosed as TSA ot TVA between 2012 and 2014 at the Flór Ferenc Hospital were retrieved and histologically reassessed by two pathologists.

Results: A total of 115 polyps diagnosed as TSA or TVA were reviewed and 11 polyps were selected and classified as TSA on the basis of the current diagnostic criteria. As a control group, we studied 104 TVAs and determined the same features. Both ECF and typical cytology were seen in 10 of the 11 TSAs (91%), luminal serration was present in 73%. To the extent of more than 50% of the polyp, typical cytology was noted in 7 cases (64%), ECF and luminal serration was seen in 3 TSAs (27%). Of the 104 TVAs, typical cytology was present in 35 cases (34%), ECF was found in 9% and luminal serration was noted in 20%. Typical cytological features were seen only in 3 TVAs (3%) to the extent of more than 50% of the adenoma. Luminal serration in more than half of the specimen was seen only in one TVA. The presence of all three morphological features simultaneously was observed in 6 of the 11 TSAs (55%), and only in 3 of the 104 TVAs (3%). Two TVAs showed typical TSA-like patterns to a considerable degree.

Conclusion: In conclusion, ECF proved to be the most helpful morphological feature regarding the diagnosis of TSA, although it is not specific to TSA and is not seen in every case of TSA. Luminal serration and TSA-like cytology are frequently present in TVAs, but they are only visible in extreme cases in more than 50% of the adenoma. Some polyps show a mixed morphology, with TSA-like and conventional adenoma-like areas. These cases may be regarded as mixed polyps.

Disclosure of Interest: None declared

P0411 1H HR NMR SPECTROSCOPY OF FECAL EXTRACTS ENABLES DETECTION OF ADVANCED COLORECTAL NEOPLASIA

A. Amiot¹², A. Dona¹, A. Wijeyesekera¹, C. Tournigand³, Y. Lebaleur², I. Sobhani², E. Holmes¹

¹Section of Biomolecular Medicine, Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom, ²Department of Gastroenterology, ³Deartment of Oncology, CHU Henri Mondor, EC2M3, APHP, UPEC, Creteil, France

Contact E-mail Address: aurelien.amiot@hmn.aphp.fr

Introduction: Colorectal cancer (CRC) is a growing cause of mortality in developing countries warranting investigation into its etiopathogenesis and earlier diagnosis. Here, we assessed the value of fecal metabolic phenotype of patients with advanced colorectal neoplasia and controls using ¹H-nuclear magnetic resonance (NMR) spectroscopy.

Aims & Methods: Fecal extract samples from 55 patients with advanced colorectal neoplasia and control patients, were evaluated using ¹H-nuclear magnetic resonance (NMR) spectroscopy. Unsupervised (principal component analysis) and supervised (orthogonal partial least-squares discriminant analysis OPLS-DA) multivariate analyses were applied to discriminate between samples using MATLAB (v.2013a) and SIMCA-P+ (v.13.0.1) softwares. The 7-fold cross validation, a 1000 permutation testing and determination of the area under the receiver operator characteristics curves (AUROC) were applied for internal validation. Wif-1 methylation levels in stools, serum and urine and seven dominant and subdominant bacterial populations in stools were quantified and correlated to metabolic profile of each patients.

Results: The predictability of the model was 0.507 (Q2Y) and the explained variance was 0.755 (R2Y). The goodness of fit and predictive capability (Q²) of the ¹H-NMR OPLS-DA model remained higher than those of the 1000 permutated models indicating that the model was statistically robust. Patients with advanced colorectal neoplasia disclosed increased signals of four short-chain fatty acids (valerate, acetate, propionate and butyrate) and decreased signals of β-Glucose, glutamine and glutamate. The predictive accuracy of the ¹H-NMR OPLS-DA model for predicting advanced colorectal neoplasia (AUROC = 0.94, IC95% [0.84-0.99]) was higher than FOBT (0.71, IC95% [0.56-0.83], p = 0.0001) and the serum and/or urine Wif-1 methylation test (0.81, IC95% [0.68-0.91], p = 0.03). Correlation analysis of the microbiome and metabolome data revealed strong associations between Faecalibacterium prausnitzii and Clostridium leptum species and butyrate and valerate concentration and inverse correlation between Faecalibacterium prausnitzii and glucose.

Conclusion: ¹H-NMR spectroscopy of fecal extract samples identified a specific metabolic signature that clearly distinguish patients with advanced colorectal neoplasia from the controls. These preliminary results suggest that urinary metabolomics may have a future potential role in non-invasive colorectal screening program.

Disclosure of Interest: None declared

P0412 IRON DEFICIENCY ANAEMIA; APPROPRIATE SEQUENCE OF ENDOSCOPIC INVESTIGATIONS

A. Rehman¹, B. Natarajan¹, B. Javaid¹

¹Bedford Hospital, Bedford, United Kingdom

Contact E-mail Address: amerrehman964@yahoo.co.uk

Introduction: Iron deficiency anaemia (IDA) is present in 2-5% of men and post-menopausal women and is a common reason for gastroenterology referral (1, 2). British society of gastroenterology recommends an upper and lower gastrointestinal (GI) endoscopy to rule out pathology including malignant disease (2). Traditionally an oesophago-gastro-duodenoscopy (OGD) is performed first followed by colonoscopy. This retrospective study evaluates the usefulness of this strategy.

Aims & Methods: We analysed our endoscopy database to look for patients who underwent both an OGD and colonoscopy to investigate IDA over a period of one year to 31 December 2014. Further data was collected from the clinical letters and hospital pathology database. Results were evaluated using Microsoft excel.

Results: A total of 204 patients were investigated including 113 (55%) female and 91 (45%) male patients. Among these 20 (10%) patients had upper GI symptoms, 48 (23%) had lower GI symptoms and 6 (3%) had both upper and lower GI symptoms. Remaining 136 (67%) patients were asymptomatic. In the studied group, 93 (46%) had haemoglobin less than 100g/L, 54 (26%) had Haemoglobin 100-109 g/L, 31 (15%) had haemoglobin 110-120 g/L and 26 (13%) had haemoglobin more than 120g/L. Ferritin levels were less than the lab cut off in 158 (78%), less than 50 but above the lab cut off in 26 (13%), between 50 and 100 in 11 (5%) and >100 in 8 (4%). OGD was normal in 108(53%) patients. Gastritis was found in 29 (14%), Large hiatus hernia in 22 (11%), oesophagitis in 14 (7%), gastric polyp in 12 (6%) and other findings were found in 19 (9%) including 1 gastric malignancy. Duodenal biopsies were normal in 178 (87%) and not taken in 22 (11%). Coeliac was diagnosed in 1 (<1%). Colonoscopy results showed normal findings in 81 (40%), diverticulosis in 42 (21%), polyps in 33 (16%), Haemorrhoids in 31 (15%), Malignancy in 17 (8%) and others in 15 (7%). Among those with polyps adenomatous polyps were confirmed on histology in 20 (10%) and hyperplastic in 13 (6%). Caecal intubation rate was an acceptable being 91% (186) with 18 (9%) patients having completion Virtual colonogrpahy (Computerised tomography). Coeliac serology was not checked for 150 (74%). It was negative in 53 (26%) and was positive in 1 (<1%). Importantly the only one patient with gastric malignancy did not have any upper or lower GI symptoms. Among patients with colonic malignancy 3 (18%) patients had lower GI but no upper GI symptoms.

Conclusion: This study showed that 17 (8%) patients had colonic malignancy while only 1 (<1%) had upper GI malignancy. Hence we would recommend colonoscopy as the initial endoscopy procedure instead of an OGD when investigating iron deficiency anaemia both in asymptomatic patents and those who present with lower GI symptoms

Disclosure of Interest: None declared

P0413 “SCORE SYSTEM” FOR CARDIOVASCULAR RISK: A TOOL TO SELECT PATIENTS AT HIGH RISK FOR COLORECTAL NEOPLASIA

C. J. Gargallo¹, P. Carrera², C. Scarpignato³, A. Lanas⁴

¹Gastroenterology, University Hospital “ Lozano Blesa", ²Ciberehd, zaragoza, Spain, ³Pharmacology, University of Parma, Parma, Italy, ⁴gastroenterology, University Hospital Lozano Blesa, zaragoza, Spain

Contact E-mail Address: carlajerusalen@hotmail.com

Introduction: Cardiovascular (CV) disease and colorectal cancer (CRC) are important health problems worldwide and share several risk factors. Little is known about the risk of colorectal neoplasia (adenomas or CRC) among individuals at different risk for CV disease. European Guidelines on CV disease prevention recommend the SCORE system to assess the total CV risk in apparently healthy persons.

Aims & Methods: To evaluate: 1) the prevalence of colorectal neoplasia in an average CRC risk population according to the individual CV risk, 2) the relationship between the CV risk and type of colorectal neoplasia (non advanced adenoma, advanced adenoma [AA] and CRC).

Results: 605 patients were included in this study. The mean age was 59.7 ± 11.6 years, and there were 311 men (51.4%). 9.8% of patients were diabetic and 23.8% were smokers. 223 patients (36.9%) had 1 or more colorectal neoplasias. The prevalence of colorectal neoplasia in patients with low CV risk, intermediate CV risk and high/very high CV risk was 8.3% (9/109), 41.6% (126/303) and 45.6% (88/193), respectively (p< 0.001). The prevalence of advanced colorectal neoplasia (AA or CRC) was 4.6% (5/109), 24.1% (73/303) and 34.7% (67/193), respectively (p< 0.001). In multivariate analyses, the moderate risk group and the high/very high risk group had a significantly increased risk of colorectal neoplasia compared with the low risk group, [Odds Ratio (OR) 5.69 (95% confidence interval (CI), 2.41-13.42)] and [OR 5.62 (95% CI, 1.99-15.89)], respectively, (p=0.001). The moderate risk group and the high/very high risk group had also a significantly increased risk of advanced colorectal neoplasia compared with the low risk group [OR 5.43 (95% CI, 1.86-15.88)] and [OR 8.56 (95% CI, 2.46-29.79)], respectively, (p=0.001). The high/very high risk group had a non-significantly increased risk of advanced colorectal neoplasia compared with the moderate risk group [OR 1.58 (95% CI, 0. 96- 2.60), p = 0.075].

Conclusion: The prevalence and risk of overall and advanced colorectal neoplasia increase in parallel with the risk of death due to CV disease. The SCORE system may be used as a predictive risk model of colorectal neoplasia. Hence, patients at increased CV risk may benefit from CRC screening.

Disclosure of Interest: None declared

P0414 IS THE INFORMATION PROVIDED ON HISTOPATHOLOGY REQUEST FORMS FOR COLORECTAL CANCER ADEQUATE?

C. Ntala¹, A. Gumber¹, G. Kaur¹

¹Surgery, Scunthorpe General Hospital, Scunthorpe, United Kingdom

Contact E-mail Address: gkaur@email.com

Introduction: Surgical pathology depends heavily on the input of clinicians and surgeons. The pathologist’s need for adequate clinical information before diagnosis can be made has been highlighted in the past. According to the Royal College of Pathologists’ UK guidelines for reporting colorectal cancer, histopathology requests need (1) a diagram of the surgical procedure, (2) if the cancer has been detected as part of the bowel cancer screening programme, (3) the histological type of tumor if known, (4) a history of inflammatory bowel disease/ familial cancer, (5) the pre-operative stage of tumor, (6) any pre-operative therapy has been given, when it finished and its nature, (7) if open, laparoscopic or robotic surgery has been performed, the type and dissection plane of the operation.

Aims & Methods: We aimed to audit the quality of clinical information provided in colorectal cancer resection histology requests for the past 5 years in our hospital.

Data was collected for 500 patients with large bowel cancer resections between 2/12/2009 and 18/11/2014

Results: Of 498 histology request forms, only two had a diagram present (0.4%) and three (0.6%) reported that the tumor was detected in the bowel cancer screening programme. The histological type was reported in 72 out of 496 samples (14.52%) and the presence of IBD or familial cancer was reported in 2 out of 497 (0.4%). The pre-operative stage of tumor was recorded in 27 out of 496 reports (5.4%) and the pre-operative therapy given in 56 out of 496 (11.3%). Finally, the type of surgery and dissection were adequately documented in 221 out of 497 reports (44.5%).

Conclusion: Overall, the quality of reporting of clinical information in histology reports remains suboptimal. This audit identified important areas in which reporting quality needs to be improved.

Disclosure of Interest: None declared

P0415 PREDICTIVE FACTORS OF PARTICIPATION IN SURVEILLANCE PATIENTS WITH HIGH-RISK ADENOMAS

A. Fernandez¹, D. Zaffalon¹, A. Garcia¹, L. Marquez¹, L. Carot¹, C. Alvarez¹, X. Bessa¹, M. Andreu¹, F. Macia²

¹Gastroenterology, ²Epidemiology, Hospital Del Mar, Barcelona, Spain

Contact E-mail Address: agnesfc07@gmail.com

Introduction: A good adherence to surveillance programs of people with high-risk adenomas (AAR) is essential to reduce the incidence of colorectal cancer. Identifying predictors of participation could improve the efficiency of this program, through the implementation of improvement measures.

Aims & Methods

Objective: To evaluate the possible predictors of participation and non-participation in a program of colonoscopy surveillance of individuals with AAR, and to assess the impact of reminder measures.

Methods: Analysis of 627 cases from the population screening program of CCR from Ciutat Vella Sant Martí, who had been recommended to colonoscopy surveillance after 3 years because of having high-risk adenomas (advanced adenoma and / or multiplicity) in baseline colonoscopy performed at the Hospital del mar during the years 2010-2011. Individuals who did not participate received a phone call reminder.

Results: We identified a total of 627 cases, 418 men (66%) with average age 63.6± 5.2 years. After 3 years a colonoscopy surveillance was done in 407 cases (64.9%) and it was completed in 387 cases (95%). The causes of non-performing colonoscopy in 220 cases were: to be performed (scheduled or requested) in 131 (59%) cases, ignorance of the need of control in 26 (11.7%) cases, individual negative in 11 (5%) cases, contraindicated in 3 (1.4%) cases, in 3 cases (1.4%) changed place of living and deaths in 10 (4.5%) cases.

There were no significant differences in participation because of age, sex, toxic habits, place of birth or social status. The use of statins and regular exercise were independently associated with a greater involvement (p = 0.035 and p = 0.007). With regard to comorbidity, the presence of renal failure and dyslipidemia showed a trend towards greater participation, but not significant (p = 0.089 and p = 0.09). A phone call was performed in 114 cases, contacted in 86 patients who had not made the follow up colonoscopy (39.1%). This call led to a change of attitude in 45 cases (59.2%), mostly associated with the group that did not made because of ignorance (66%), compared to other reasons (p = 0.001). In the group of non-participation because of individual negative it made a change of attitude in 17% of cases.

Conclusion: The most frequent reason for non-participation in colonoscopy surveillance program in individuals with high-risk adenomas is ignorance. A phone call reminder produces a significant impact on their attitude.

Disclosure of Interest: None declared

P0416 PROSPECTIVE MULTICENTER STUDY OF A FLEXIBLE SELF-EXPANDABLE METALLIC STENTS FOR MALIGNANT COLORECTAL OBSTRUCTION IN JAPAN: SHORT-TERM SAFETY AND EFFICACY IN 199 PATIENTS

A. Narita¹, S. Yoshida², H. Isayama¹, T. Yamada³, I. Maetani⁴, Y. Sumida⁵, R. Kyo⁶, T. Kuwai⁷, M. Tomita⁸, R. Moroi⁹, T. Matsuzawa¹⁰, S. Saito¹¹, T. Sasaki¹, Y. Saida¹²

¹Dept. of Gastroenterology, Graduate School of Medicine, the University of Tokyo, ²Dept. of Endoscopy and Endoscopic Surgery, the University of Tokyo, Tokyo, ³Dept. of Gastroenterology, Nagoya Daini Red Cross Hospital, Nagoya, ⁴Div. of Gastroenterology and Hepatology, Toho Ohashi Medical Center, Tokyo, ⁵Dept. of Gastroenterology, National Hospital Organization Kyushu Medical Center, Fukuoka, ⁶Dept. of Gastroenterology, Saiseikai Yokohama-Nanbu Hospital, Yokohama, ⁷Dept. of Gastroenterology, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, ⁸Dept. of Surgery, Kishiwada Tokushukai Hospital, Osaka, ⁹Dept. of Gastroenterology, Iwate prefectural Isawa Hospital, Oshu, ¹⁰Dept. of Digestive Tract and General Surgery, Saitama Medical Center,Saitama Medical University, Kawagoe, ¹¹Dept. of Surgery, Gastrointestinal Center Yokohama Shin-Midori General Hospital, Yokohama, ¹²Dept. of Surgery, Toho University Ohashi Medical Center, Tokyo, Japan

Contact E-mail Address: naribo_maro@yahoo.co.jp

Introduction: After endoscopic stenting with self-expandable metallic stent (SEMS) was covered by government medical insurance in Jan. 2012, this procedure is widely adapted in Japan. With an approval of a new flexible SEMS by insurance in July 2013, we conducted a prospective feasibility study of this SMES.

Aims & Methods: Our objectives were to estimate safety and feasibility of a new SEMS placement for malignant colorectal obstruction in general clinical practice in Japan. We conducted a prospective, observational, single-arm and multicenter clinical trial from Oct. 2013 to May. 2014. This study was registered with UMIN Clinical Trial Registry (UMIN000011304). Thirty two facilities consisted of 7 academic and 25 community hospitals participated this study. Ahead of this study, we launched a website (http://colon-stent.com/) and pronounced the standard methods based on previous published data to standardize the maneuver of SEMS placement. Each patient was treated with a Niti-S Enteral Colonic Uncovered Stent, D-type. SEMSs were deployed under fluoroscopy and endoscopy. Technical success was defined as placement of the stent across the entire length of the stricture on the first attempt. Clinical success was defined as a resolution of symptoms and radiological relief of the obstruction within 24h. Patients undergoing the stenting as a bridge to surgery (BTS) were followed until surgery, and incurable patients undergoing palliative treatment (PAL) were followed until death or 12 months, whichever came first. The following conditions were considered to be complications: stent occlusion, insufficient expansion of stent, obstruction of the other gastrointestinal site, stent migration, perforation, tenesmus, abdominal pain, pneumonia and bacteremia. Complications were categorized as early (within 7 days) or late (after 7 days). In this analysis, we estimate the early complications.

Results: We registered 205 patients. Six patients were excluded for analysis, because of loose stenosis with passed by colonoscope (2), benign stricture (1), inability to visualize the tumor (1), fistula (1), and deterioration of respiratory condition during the procedure (1). We enrolled 199 patients for a BTS (112) and PAL (87) indication for a per-protocol analysis (PPA). In PPA, technical and clinical success was 98% (BTS : 99.1%, PAL : 97.7%) and 97% (BTS : 98.2%, PAL : 95.4%). Within 7 days after SEMS placement, the overall complication rate was 4.0% (3.6% BTS, 4.6% PAL), including abdominal pain (1.5%), insufficient expansion (1.5%), stent occlusion (1.0%), obstruction of the other gastrointestinal site (1.0%), stent migration (0.5%), death (0.5%) and pneumonia (0.5%). There was no perforation.

Conclusion: This study demonstrates the feasibility of a new flexible SEMS placement for malignant colorectal obstruction. Within 7days after SEMS placement, the incidence of complications was relatively low as well as no perforation.

Disclosure of Interest: None declared

P0417 TUMOR DIAMETER IS AN EASY AND USEFUL PREDICTOR OF RECURRENCE IN STAGE II COLORECTAL CANCER

C. Maeda¹, E. Hidaka¹, Y. Mori¹, S. Mukai¹, H. Miyachi¹, N. Sawada¹, F. Ishida¹, S.-E. Kudo¹

¹Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan

Contact E-mail Address: maechiyo@hotmail.co.jp

Introduction: Adjuvant chemotherapy for stage II colorectal cancer can generally be administered to high-risk subgroups. The ASCO and ESMO have stated 9 risk factors associated with recurrence of stage II colorectal cancer. The risk factors are defined as patients with ≤ 12 sampled lymph nodes, a T4 lesion, perforation, poorly differentiated histology, vascular invasion, lymphatic vessel invasion, perineural invasion, obstruction, or a high carcinoembrionic antige level. To better identify these patients, we aimed to assess factors that affect recurrence.

Aims & Methods: In our hospital, 432 colon and 96 rectal stage II cancer patients who underwent surgical resection between 2001 and 2011 were divided into recurrence and non-recurrence groups. Age, sex, lymphatic vessel invasion, venous invasion, tumor diameter, tumor depth, histological type, preoperative carcinoembryonic antigen level, number of sampled nodes, adjuvant chemotherapy, morphology, surgical approach, anastomotic leakage, preoperative bowel obstruction, and preoperative perforation were retrospectively compared between the groups.

Results: For colon cancer, multivariate analysis revealed a significant association between tumor diameter ≥ 40 mm and recurrence (p = 0.039). For rectal cancer, multivariate analysis revealed that tumor diameter ≥ 50 mm (p = 0.001) and ≤ 12 sampled nodes (p = 0.021) were associated with recurrence. Tumor diameter in rectal cancer was associated with worse disease-free survival (p = 0.026).

Conclusion: Tumor diameter is a significant predictor of recurrence in stage II colorectal cancer. This is an important finding because tumor diameter is easy to evaluate clinically and might help to identify candidates for adjuvant chemotherapy.

Disclosure of Interest: None declared

P0418 CUMULATIVE INCIDENCE OF COLORECTAL NEOPLASIA DURING ENDOSCOPIC SURVEILLANCE IN SERRATED POLYPOSIS SYNDROME (SPS) PATIENTS: A MULTICENTER STUDY

D. Rodríguez-Alcalde¹, S. Carballal², L. Moreira², L. Hernández¹, L. Rodríguez³, F. Rodríguez-Moranta³, V. Gonzalo⁴, L. Bujanda⁵, X. Bessa⁶, C. Poves⁷, J. Cubiella⁸, I. Castro⁸, M. González⁹, E. Moya¹⁰, S. Oquiñena¹¹, J. Clofent¹², E. Quintero¹³, P. Esteban¹⁴, V. Piñol¹⁵, F. J. Fernández¹⁶, R. Jover¹⁷, L. Cid¹⁸, E. Saperas¹⁹, M. López-Cerón², M. Cuatrecasas²⁰, J. López-Vicente¹, M. L. Leoz², L. Rivero², A. Castells², M. Pellisé², F. Balaguer², on behalf of Gastrointestinal Oncology Group of the Spanish Gastroenterological Association

¹Digestive Disease Section, Hospital Universitario de Móstoles, Móstoles, ²Gastroenterology Department, Hospital Clínic de Barcelona, Barcelona, ³Gastroenterology Department, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, ⁴Gastroenterology Department, Hospital Universitari Mútua de Terrassa, Terrassa, ⁵Gastroenterology Department, Hospital Donostia/Instituto Biodonostia, San Sebastián, ⁶Gastroenterology Department, Hospital del Mar, Barcelona, ⁷Gastroenterology Department, Hospital Clínico San Carlos, Madrid, ⁸Gastroenterology Department, Complexo Hospitalario Universitario de Ourense, Ourense, ⁹Gastroenterology Department, Hospital Puerta de Hierro, Madrid, ¹⁰Gastroenterology Department, Hospital Universitario del Sureste, Arganda del Rey, ¹¹Gastroenterology Department, Complejo Hospitalario de Navarra, Pamplona, ¹²Gastroenterology Department, Hospital de Sagunto, Sagunto, ¹³Gastroenterology Department, Hospital Universitario de Canarias, Santa Cruz de Tenerife, ¹⁴Gastroenterology Department, Hospital Universitario Morales Meseguer, Murcia, ¹⁵Gastroenterology Department, Hospital Josep Trueta, Girona, ¹⁶Gastroenterology Department, Hospital de Galdakao Usansolo, Vizcaya, ¹⁷Gastroenterology Department, Hospital General de Alicante, Alicante, ¹⁸Gastroenterology Department, Complexo Hospitalario Universitario de Vigo, Vigo, ¹⁹Gastroenterology Department, Hospital General de Catalunya, Sant Cugat del Vallès, ²⁰Pathology Department, Hospital Clínic de Barcelona, Barcelona, Spain

Contact E-mail Address: drodrigueza@salud.madrid.org

Introduction: Due to the increased colorectal cancer (CRC) risk in patients with Serrated Polyposis Syndrome (SPS), annual surveillance colonoscopy with polyp removal is currently advised. However, incidence of neoplastic lesions under endoscopic surveillance remains poorly studied and current recommendations are based on low-quality evidence.

Aims & Methods: We aim at describing colorectal neoplasia incidence in SPS under endoscopic surveillance. From March 2013 through April 2015, SPS patients were retrospectively recruited at eighteen Spanish centers. Data were collected from medical, endoscopy and histopathology reports. We included those patients who, after a successful clearing colonoscopy, underwent endoscopic surveillance with an interval up to 3 years. Patients with total colectomy were excluded. Cumulative incidence of neoplasia [CRC, advanced adenomas, serrated polyps (SP) with high-grade dysplasia (HGD), SP ≥10mm, proximal SP and proximal sessile serrated adenomas (SSP)] was calculated by Kaplan-Meier survival analysis. Advanced SP was defined as ≥10 mm and/or SP with HGD and/or proximal SP.

Results: In 158 SPS patients with a median follow-up time of 25.6 months (range: 6.4-129.1) a total of 321 surveillance colonoscopies were performed (median: 2, range: 1-7). Mean age at SPS diagnosis was 55.5 years (SD: 10.0) and 71 (44.9%) were female. Median time between procedures was 13.7 months (range: 6.0-35.8). Four invasive CRC were detected during surveillance (3-year cumulative risk: 3.0%). Three-year cumulative incidence of colorectal polyps was as follows: advanced adenomas, 12.4%; SP with HGD, 0.9%; SP ≥10mm, 32.5%; proximal SP, 72.8%; proximal SSP, 30.8%. The cumulative risk of advanced SP under surveillance was 74.3% and 87.9% at 3 and 5 years, respectively. During follow-up, 10 (6.3%) patients were referred for surgery due to an invasive CRC (n=4, 2.5%) or severe polyposis (n=6, 3.8%).

Conclusion: Whereas SPS patients under endoscopic surveillance show a considerable risk of polyp recurrence, the majority of them can be managed endoscopically. Cumulative risk of CRC under close endoscopic surveillance seems to be low. Further studies are needed to define high-risk patients in order to tailor surveillance strategy.

Disclosure of Interest: None declared

P0419 ENDOSCOPIC TREATMENT ALONE OR COMPLEMENTARY SURGERY FOR T1 COLORECTAL CANCER – IS THERE STILL ROOM FOR OPTIMIZING CURATIVE RESSECTION CRITERIA?

D. Branquinho¹, N. Almeida¹, P. Monsanto¹, M. A. Cipriano², P. Amaro¹, F. Portela¹, L. Prado², C. Sofia¹

¹Gastroenterology, ²Pathology, Coimbra University Hospital (CHUC), Coimbra, Portugal

Contact E-mail Address: diogofbranquinho@yahoo.com

Introduction: Up to 9% of colorectal polyps may conceal an adenocarcinoma with submucosal involvement (Malignant Polyp). Careful surveillance or complementary surgery after endoscopic are accepted treatment strategies. Identifying high-risk patients remains challenging, as oncologic results are a priority while unnecessary surgery should be avoided

Aims & Methods: Our objective was to evaluate oncologic results of endoscopic excision of T1 colorectal with or without complementary surgery.

A total of 121 patients were included between 2003-2007 and 2010-2014 (male patients – 74.4%; average age – 68.5 ± 10.6 years; follow-up: 30 ± 20 months). Clinical, endoscopic and histological features were analyzed. Unfavorable outcome was defined as residual lesion after endoscopic excision, regional or distant metastasis, recurrence or disease-related deaths.

Results: All 121 identified lesions were subject to endoscopic treatment. About 43.4% (53/121) of those were submitted to surgery as well. The most relevant criteria for surgical referral were the presence of lymphatic/vascular invasion (p=0.001), involved margins (p=0.014) and being under 65 years-old (p=0.02).

Residual cancer cells were identified in only 12.2% of surgical specimens (7/53) and 10.7% of patients had an unfavorable outcome. Univariate analysis revealed that incomplete or piecemeal endoscopic excision (p=0.046), free margin <1 mm (p=0.028) and the need for surgical treatment (p=0.012) are associated with an unfavorable prognosis.

There was no significant difference in procedure-related complications between the two groups (surgery vs endoscopy alone), with one death due to perforation during an endoscopic procedure.

Conclusion: Overall, we can affirm that the treatment of these lesions is safe and efficacious. However, the presence of incomplete endoscopic excision, positive margins and the need of complementary surgery is associated with worse prognosis. The large majority of surgical specimens had no residual cancerous lesion, suggesting that criteria for referral should be improved in order to avoid unnecessary surgery.

Disclosure of Interest: None declared

P0420 EASY AND DIFFICULT COLORECTAL ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD): PROSPECTIVE STUDY TO SAFELY SPEED UP WESTERN EXPERIENCE

F. Iacopini¹, Y. Saito², T. Gotoda³, W. Elisei¹, C. Grossi¹, F. Montagnese¹, G. Costamagna⁴, L. Pacilli⁵, A. Scozzarro¹

¹Gastroenterology & Endoscopy Unit, Ospedale S. Giuseppe, Albano L., Rome, Italy, ²Endoscopy Division, National Cancer Center Hospital, ³Department of Gastroenterology & Hepatology, Tokyo Medical University, Tokyo, Japan, ⁴Surgical Digestive Endoscopy, Catholic University, Rome, ⁵Anesthesiology Unit, Ospedale S. Giuseppe, Albano L., Rome, Italy

Contact E-mail Address: federico.iacopini@yahoo.it

Introduction: Endoscopic submucosal dissection (ESD) achieves significantly higher en bloc and R0 resection rates than endoscopic mucosal resection (EMR) and represents the best technique to achieve the curative resection of gastrointestinal superficial neoplasms. Although a level of competence can be achieved in the Western world through a stepwise training, it is unclear if it is sufficient to safely adopt ESD for colorectal lesions.

Aims & Methods: Aim was to identify pre-operative patient and lesion features prognostic of successful ESD. A prospective single center study conducted by an endoscopist who achieved an initial level of competence in colorectal ESD. Inclusion criteria were: colorectal neoplasms either ≥15 or ≥20 mm associated or not to a scar, respectively; no features of SM-deep invasion (pit pattern V associated with a demarcation area). ESD was performed by the standard technique without expert supervision. The multivariate analysis was used to identify prognostic variables of successful ESD (en bloc resection). The following variables were evaluated: patient age and sex; location in different colorectal segments; location on fold; morphology; size (cm2); nodularity (>20 mm); scar of a previous resection; endoscopist experience.

Results: From March 2010 to July 2014, ESD was attempted in 106 patients (mean age 66; females 43%) for 114 lesions (median size 10 cm², range 1-85). Lesions were 85 (75%) in the colon, 29 (25%) in the rectum; LST-G 70 (61%), LST-NG 35 (31%), Is 9 (8%); with scar 11 (10%) and a nodule in 27 (24%).

En bloc, R0, and curative resection rates were achieved in: 92 (81%), 90 (79%), 86 (75%). SM invasion was diagnosed in 13 (11%). Perforation occurred in 5 (4%) without precluding a successful ESD in 3. Prognostic variables of successful ESD in colon at the multivariate analysis are reported in the Table; no significant variables were identified for rectal ESD.

	OR (95% CI)	P=
Age	1.11 (1.01-1.23)	0.037
Location in fixed looping segments	0.14 (0.02-0.78)	0.025
Size diameter >40 mm	0.08 (0.01-0.46)	0.005
Scar presence	0.02 (0.01-0.33)	0.007

Conclusion: A level of competence in colorectal ESD is not sufficient for a widespread adoption of ESD in the colon. Superficial neoplasms at a very high level of difficulty for ESD are colonic either located in the cecum or flexures, larger than 40 mm, and associated with a scar. Western endoscopists without expert supervision should avoid ESD of very difficult lesions until an expertise level has been achieved.

Disclosure of Interest: None declared

P0421 THE THERAPEUTIC EFFECT OF IRREVERSIBLE ELECTROPORATION ABLATION IN MOUSE MODEL OF COLORECTAL CANCER

H. S. Choi¹, H. J. Chun¹, I. K. Yoo¹, J. M. Lee¹, S. H. Kim¹, E. S. Kim¹, B. Keum¹, Y. T. Jeen¹, H. S. Lee², C. D. Kim², J. Y. Kim³

¹Internal Medicine, Institute of Gastrointestinal Medical Instrument Research, Korea University College of Medicine, ²Internal Medicine, ³Pathology, Korea University College of Medicine, Seoul, Republic of Korea

Introduction: Irreversible electroporation (IRE) is a promising novel technique for the ablation of tumors. IRE has an advantage over other ablation techniques in its mechanism to remove undesired cells by affecting the cell membrane without thermally destructing blood vessels, nerves and the surrounding tissues. Studies regarding the clinical application of IRE have been performed in humans, as well as in animals, for organs such as the liver, kidney, prostate, etc. and IRE is now accepted as a novel anti-cancer ablation modality.

Aims & Methods: The aim of this study was to evaluate the therapeutic effect of IRE in mouse model of colorectal cancer for the first time. The Caco2 cells (ATCC) were cultured in petri-dishes. Male nude mice (Immunodeficient (CAnN.Cg-Foxn1 nu/CrljBgi) 6 weeks old, Orient inc., Korea) were introduced. Caco2 cells were each visually injected at 1.0 x 10⁷ cells/ml into both flakes (one for control, the other for IRE). We performed in vivo IRE procedures in the tumors of nude mouse model. Electrical pulses were applied to the tumor of nude mouse using a DC generator at 1∼2kV/cm amplitude, 20∼50 pulses, 100 < length, with 1mm separation between two needle type electrodes. We analyzed the tissues with H&E staining and TUNEL assay immediately afterwards, and then 10 hours, 24 hours.

Results: All mice were preserved during the experiment without significant complications. There was complete cell death within the IRE lesions without intervening live cells. Variable nucleic changes-pyknosis and karyohexis, and vacuolar degeneration were observed only within the IRE lesions. The framework of extracellular matrix and blood vessels were not affected by IRE. The apoptotic area and signals were increased in IRE groups comparing control groups in tunnel assay.

Conclusion: The present study demonstrated that IRE ablated colon cancer tissue very effectively through the induction of cellular apoptosis. This study suggests that IRE is the potential use of IRE in gastrointestinal cancer patients.

Disclosure of Interest: None declared

P0422 THE EFFECT OF HMG-COA REDUCTASE INHIBITOR ON NF-E2-RELATED FACTOR 2 (NRF2) ACTIVATION IN COLON CANCER CELLS

H. J. Jang¹, S. W. Park¹, D. H. Koh¹, M. H. Choi¹, S. H. Kae¹, J. Lee¹

¹Hallym University Dongtan Sacred Heart Hospital, Hwasung, Republic of Korea

Contact E-mail Address: jhj1229@hallym.or.kr

Introduction: Statin has been ascribed not only to their cholesterol lowering effect but also to their pleiotropic actions including anti-inflammatory and anti-oxidant effects as well as anti-neoplastic effect. Nrf2 (NF-E2-related factor 2) is a transcription factor that control the transcriptional response of cells to oxidative stress. There are little known how statins affect activation of Nrf2 and Nrf2 signaling pathway in colon cancer cells.

Aims & Methods: We investigated the effect of simvastatin on expression of Nrf2 and nuclear translocation of Nrf2 in two colon cancer cell lines, HT-29 and HCT 116 by cell proliferation assay, western blotting and immunocytochemical analysis. We also investigated which signal cascade such as ERK or PI3K pathway control nrf2 activation and whether simvastatin affects induction of antioxidant enzymes (heme oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase 1 (NQO1), γ-glutamate-cysteine ligase catalytic subunit (GCLC)).

Results: We demonstrated simvastatin induced dose-dependent upregulation of Nrf2 expression and anti-oxidant enzymes (HO-1, NQO1, and GCLC) in HT-29 and HCT 116 cells. We demonstrated that simvastatin stimulated Nrf2 nuclear translocation. In addition, PI3K/Akt inhibitor (LY294002) and ERK inhibitor (PD98059) blocked simvastatin induced Nrf2 and HO-1 expression in both HT-29 and HCT 116 cells.

Conclusion: In this study, we show that simvastatin induces Nrf2 activation and nuclear translocation of Nrf2 and expression of anti-oxidant enzymes via ERK and PI3K/Akt pathway in colon cancer cells.

Disclosure of Interest: None declared

P0423 CAP-ASSISTED ENDOSCOPIC MUCOSAL RESECTION FOR RECTAL NEUROENDOCRINE TUMORS: COMPARISONS WITH CONVENTIONAL ENDOSCOPIC MUCOSAL RESECTION AND ENDOSCOPIC SUBMUCOSAL DISSECTION

J.-M. Lee¹, D.-H. Yang¹, Y. Park², M. S. Kwak¹, W. S. Kim¹, S. W. Hwang¹, S. H. Park¹, K.-J. Kim¹, B. D. Ye¹, J.-S. Byeon¹, S.-K. Yang¹

¹Gastroenterology, ²Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

Contact E-mail Address: fellowmi@naver.com

Introduction: The incidence of rectal neuroendocrine tumors (NETs) is increasing, and most rectal neuroendocrine tumors with a size <15 mm can be treated endoscopically. Given that almost all rectal NETs involve the submucosal layer or deeper layers of the rectal wall, conventional endoscopic mucosal resection (EMR) may not be suitable for achieving high en bloc and histologic complete resection. Cap-assisted endoscopic mucosal resection (EMR-C) was suggested as an effective treatment for rectal NETs in a few studies.

Aims & Methods: We aimed to compare the outcomes of conventional endoscopic mucosal resection (EMR), EMR-C resection, and endoscopic submucosal dissection (ESD) for the treatment of rectal NETs. A total of 138 rectal NETs < 15mm in diameter were treated endoscopically by a single endoscopist at Asan Medical Center from 2009 to 2014. We retrospectively analyzed 122 rectal NETs that had been removed using EMR (n = 56), EMR-C (n = 34), or ESD (n = 32) methods.

Results: The mean size of the rectal NETs was larger in the ESD group (9.1 ± 2.2 mm; range, 6–14 mm) than in the EMR group (5.0 ± 1.8 mm; range, 2–13 mm) and the EMR-C (5.3 ± 1.6 mm; range, 2–8 mm) group (P < 0.001). Six (4.9%) of one hundred and twenty-two lesions were larger than 10 mm in size (five in the ESD group and one in the EMR group). The histologic complete resection rate was higher in the EMR-C group than in the EMR group (94.1% vs. 76.8%, P = 0.032). Intraprocedural bleeding tended to be more frequent in the EMR-C group than in the EMR group (8.8% vs. 0, P = 0.051). All intraprocedural bleeding was controlled easily during the endoscopic procedure. No differences in the rates of adverse events or histologic complete resections were observed between the EMR-C group and the ESD group for 6–8 mm sized NETs; however, the procedure time was significantly shorter in the EMR-C group (3.9 ± 1.1 mm) than in the ESD group (19.0 ± 12.1 minutes) (P < 0.001). Meanwhile, the role of EMR-C in the treatment of rectal NETs larger than 8 mm could not be clearly assessed in this study. No recurrence occurred in any of the three groups.

Abstract number: P0423

Comparison between EMR-C and conventional EMR, EMR-C and ESD for all rectal neuroendocrine tumors.

Number of lesions	EMR-C (n = 34)	EMR (n = 56)	p-value(EMR-C Vs. EMR)	ESD(n=32)	p-value(EMR-C Vs. ESD)
Lesion size, mean ± S.D. (range), mm	5.3 ± 1.6 (2–8)	5.0 ± 1.8 (2–13)	0.354	9.1 ± 2.2 (6–14)	<0.001
En bloc resection, n (%)	34 (100)	56 (100)	NA	32 (100)	NA
Procedure time, mean ± S.D., minutes	4.2 ± 2.0	2.1 ± 1.2	0.002	19.8 ± 11.3	0.002
Histologic complete resection, n (%)	32 (94.1)	43 (76.8)	0.032	30 (93.8)	>0.999
Intraprocedural bleeding, n (%)	3 (8.8)	0	0.051	4 (12.5)	0.705
Postprocedural bleeding, n (%)	1 (2.9)	1 (1.8)	>0.999	1 (3.1)	>0.999
Perforation, n (%)	0	0	NA	0	NA

Conclusion: EMR-C is the most advisable technique for endoscopic resection of rectal NETs with sizes equal to or smaller than 8 mm.

Disclosure of Interest: None declared

P0424  SECOND-LOOK OPERATION FOR RECURRENT COLORECTAL CANCER BASED ON INTENSIVE SURVEILLANCE CONSISTS MAINLY OF CARCINOEMBRYONIC ANTIGEN AND COLONOSCOPY AND COMPUTED TOMOGRAPHY

J.-I. Hida¹, T. Yoshifuji¹, Y. Yoshioka¹, F. Sugiura¹, K. Daito¹, J. Kawamura¹, K. Ueda¹, T. Tokoro¹, K. Okuno¹

¹Surgery, Kindai University School of Medicine, Osaka, Japan

Contact E-mail Address: hida@surg.med.kindai.ac.jp

Introduction: The usefulness of postoperative carcinoembryonic antigen (CEA) monitoring and improvements in imaging techniques have renewed enthusiasm for second-look operation (SLO) as the most effective treatment for recurrent colorectal cancer by reresection following early detection. The aim of our study is to evaluate the role of CEA and imaging techniques-directed SLO.

Aims & Methods: Seven hundred fifty-six patients with Dukes stages B and C, who had undergone curative resection, were monitored postoperatively using CEA and imaging techniques. An SLO was performed on any potentially resectable recurrence, and in addition, an SLO was done when a persistently rising CEA value was detected.

Results: Recurrence developed in 18.8% (142/756) of patients, and 90.8% (129/142) of the recurrences were detected within the first 3 years following curative resection. When comparing carcinomas of the colon with that of the rectum, the former were associated with significantly more hepatic and intraabdominal recurrences, whereas the latter had significantly more locoregional and pulmonary recurrences. Seventy-two patients underwent SLO. Of these patients, 54.2% (39/72) had all of their disease resected, and 1.4% (1/72) had no detectable disease at the SLO. Among the142 patients with recurrence, 71 (50%) patients underwent SLO. The resectable group at SLO carried a significantly better survival than the unresectable recurrence group (41.3 vs. 5.2%; P < 0.01).

Conclusion: Complete removal of colorectal cancer recurrences by SLO, on the basis of postoperative, follow-up CEA and imaging technique findings, results in improved survival.

Disclosure of Interest: None declared

P0426 THE UTILITY OF A NOVEL EX VIVO TRAINING MODEL FOR COLORECTAL ENDOSCOPIC SUBMUCOSAL DISSECTION USING A BOVINE RECTUM

J. Horii¹, O. Goto², S. Kinoshita², T. Nishizawa², A. Fijimoto², Y. Ochiai², K. Takahashi², M. Shimoda³, N. Yahagi²

¹Gastroenterology, Fukuyama Medical Center, Fukuyama, ²Division of Research and Development for Minimally Invasive Treatment, ³Pathology, Keio University School of Medicine, Tokyo, Japan

Contact E-mail Address: cdqjy411@yahoo.co.jp

Introduction: The colorectal endoscopic submucosal dissection (CR-ESD) procedure is very technically demanding because of the inherent histological and anatomical features of the human colorectum. Clinically, endoscopists should learn to perform CR-ESD on the rectum because of the lower risk of perforation and less difficulty. Training using an animal model is generally recommended before performing a CR-ESD in human. We reported the similarities of histological characteristics between the bovine rectum (B/R) and the human rectum. In light of those findings, we created a novel animal training model using B/R, which reproduces the colorectal shape and elasticity of the human colorectum. This model was made using a sponge and a B/R of appropriate length fitted in a model. The maneuverability and feeling of the ESD procedure in this model were extremely similar to that in human CR-ESD. In addition, the anatomical features of the human colorectum, including the thinner wall, the narrow lumen, the presence of angulations, and haustra folds were reproduced in this model.

Aims & Methods: Aim: To assess the utility of a new animal training model for CR-ESD.

Methods: Study1: Two endoscopists (E1, E2) without experience performing CR-ESD but with some experience in gastric ESD performed the ESD of 3-cm artificial lesions in 28 consecutive sessions using this colorectal ESD training model. The speed of the ESD procedure (s/cm²), the injury score of the muscularis propria layer (MP) (scoring 1–4: 1, no damage; 2, injury to the surface of the MP; 3, laceration of the MP; 4, perforation), the injury score of the resected specimen (1, no damage; 2, injury to marking spot; 3, cut into the resected specimen), and the rate of perforation were recorded. We evaluated the effects of this training model by comparing the results of the first 14 sessions (former period; FP) with those of the last 14 sessions (latter period: LP). Study2: A follow-up survey was performed for the clinical outcomes of the first 5 cases of colorectal ESD carried out by those two endoscopists (E1, E2). For evaluating the technical aspects of the ESD procedure, size of the lesions, procedure time, en bloc resection rate, R0 resection rate and complications were evaluated.

Results: Study1: The speed of the ESD procedure were significantly faster in the LP compared to the FP in all endoscopists: mean procedure speed (FP/LP) (s/cm²): E1, 397/195 (p=0.044); E2, 421/302 (p=0.02). The MP injury scores were significantly lower in the LP than the FP in both endoscopists (p=0.046, p=0.0071). The injury score of resected specimen were also significantly lower in the LP than the FP in both endoscopists (p=0.046, p=0.0062, respectively). Study2: The median size of the lesions were 32 (20-40) mm for E1 and 22 (12-34) mm for E2. The median procedure times were 51 (10-115) min for E1 and 57 (32-74) min for E2. En bloc resection rate were 100% (5/5) for both endoscopists, R0 resection rate were 100% (5/5) for E1 and 80% (4/5) for E2. There were no complications.

Conclusion: The utility of the novel ex vivo animal training model using B/R was demonstrated. This model has the potential to simulate CR-ESD with great similarity to that performed in humans and contribute to a safe induction of clinical colorectal ESD.

Disclosure of Interest: None declared

P0427 RESISTANCE TO GAMMA-IRRADIATION AND PPAR-GAMMA AGONISTS INDUCED APOPTOSIS IN CACO-2 COLON CANCER CELLS

P. Pierzchalski¹, P. Link-Lenczowski¹, M. Jastrzębska¹, A. Leja-Szpak¹, K. Nawrot-Porąbka¹, J. Bonior¹, J. Szklarczyk¹, M. Gonciarz², J. Jaworek¹

¹Department of Medical Physiology, Collegium Medicum Jagiellonian University, Kraków, ²Endoscopy Unit, St. Barbara District Hospital, Sosnowiec, Poland

Contact E-mail Address: piotr.pierzchalski@uj.edu.pl

Introduction: The involvement of peroxisome proliferator-activated receptors (PPARs) in the cancer cell apoptosis is a generally accepted fact. However, some reports indicate that the activation of PPARγ might be directly responsible for carcinogenesis. It is well known that the high level of heat shock proteins (HSPs) in cancer cells is associated with metastasis, poor prognosis and the resistance to radio as well as chemotherapy. HSP70 as a part of the most important systems for maintaining the viability of the cell, is known to counteract against the apoptosis. Here we report the involvement of HSP70 in anti-apoptotic action of activated PPARγ in γ-irradiated human colon cancer cells.

Aims & Methods: We have employed undifferentiated Caco-2 cells cultures as an experimental model of human colon adenocarcinoma. In this system PPAR-γ agonists (ciglitazone 1x10-6M and retinoic acid RA, 1x10-6M) induced nuclear translocation of PPAR-γ as well as HSF-1. This translocation was followed by the increase of HSP70 mRNA and protein expression. As it had been previously shown by us, cell cultures subjected to γ-radiation (photons) using the therapeutic dose of 2.5 Gy, manifested typical for apoptosis PARP degradation pattern, presenting both the native 112 KD and digested 85 KD forms. It suggests activation of caspases 3 or 6.

Results: Stimulation of the cultures with PPARγ agonists prior to the irradiation eliminated PPAR-γ nuclear translocation and PARP degradation altogether. PPARγ was found to be sequestered in the complexes with AKT-1 in cytoplasmic as well as in nuclear pool. However γ-radiation did not affect PPAR-γ agonists stimulated HSF-1 translocation and subsequent HSP70 expression. Based on the obtained results, we would like to propose a plausible molecular mechanism of chemo- and radio- resistance of colon cancer cells. In γ-irradiated cells, nuclear translocation of PPARγ is abolished and PPARγ-AKT-1 complexes are conserved in which PPARγ remains insensitive for its agonists treatment. Most likely, at the same time PPARγ agonists directly activate HSF-1 nuclear translocation and subsequent HSP70 expression. The process seems to be undisturbed by the γ-irradiation what renders the colon cancer cells resistance to apoptosis under combined chemo- and radiotherapy treatment.

Conclusion: Our results provide evidences for the anti-apoptotic action of PPARγ agonists used simultaneously with the γ-radiation due to the formation of stable complexes of PPARγ with AKT-1 in which PPARγ was restrained in inactive form. Moreover, the up-regulated HSP70, in response to PPARγ agonists in γ-irradiated cultures promotes cell survival.

Disclosure of Interest: None declared

P0428 IS VEGETARIANISM A PROTECTIVE FACTOR FOR IRRITABLE BOWEL SYNDROME? A CASE-CONTROL STUDY

I. Chirila¹², I. Morariu³, O. B. Barboi¹, A. Albusoda⁴, V. L. Drug⁵

¹Department of Gastroenterology, University of Medicine and Pharmacy „Grigore T Popa” Iasi, Romania, ²Department of Environmental Health, National Institute of Public Health - RCoPH Iasi, Romania, ³Department of Environmental Chemistry, University of Medicine and Pharmacy „Grigore T Popa” Iasi, Romania, ⁴Department of Gastroenterology, ”Sf. Spiridon” Universitary Hospital, ⁵Department of Gastroenterology, National Institute of Public Health - RCoPH Iasi, Romania, Iasi, Romania

Contact E-mail Address: chirilaioan@yahoo.com

Introduction: Diet, health and disease is one of the most frequent and less comfortable questions gastroenterologists are asked about. The role of diet in physiopathology and treatment of IBS is still under-evaluated. A predominantly vegetable diet is commonly associated with bloating and flatulence. Vegetarianism may affect gut microbiota, intestinal peristalsis and inflammation. A balanced vegetarian diet may have some health benefits, but which is its influence on IBS?

Aims & Methods: We use a case-control design; patients with IBS were selected by purposive sampling; vegetarians were recruited from gastroenterologist offices, vegetarian and health food sites, the Vegetarian Society, and from friends and relatives of participants; the control sample was randomly selected from the general population. A questionnaire was delivered to all subjects to reveal recent gastrointestinal symptoms (using GSRS), to diagnose IBS (using Rome III criteria) and to evaluate eating habits (a food frequency questionnaire based on a validated European Prospective Investigation of Cancer protocol). We conducted descriptive, bivariate, and multivariate analysis to examine the associations between food habits and IBS.

Results: We compared 47 cases of IBS patients with a control group (n=104) from the same community. Among IBS patients, only 8.5% were vegetarians and among vegetarians only 8.8% were diagnosed with IBS (OR=0.14, 0.04-0.42, CI 95%, p < 0.001), since the prevalence of IBS in general population was 15.8%. Among potential risk factors in the study, age, past history of digestive disease, canned food, processed meat, whole cereals and pulses were statistically significant predictors of IBS.

Conclusion: Although some vegetable foodstuffs can exacerbate digestive symptoms, a well-balanced and customized vegetarian diet can be a protective factor for IBS.

Disclosure of Interest: None declared

P0429 EXCESS MEDICAL DIAGNOSES IN FAMILIES OF PATIENTS WITH IRRITABLE BOWEL SYNDROME (IBS)

O. S. Palsson¹, M. van Tilburg¹, W. E. Whitehead¹

¹Medicine, University of North Carolina, Chapel Hill, United States

Contact E-mail Address: opalsson@med.unc.edu

Introduction: Previous studies have shown that IBS patients as a group have an excess of co-morbid chronic medical conditions. Past work has also indicated intergenerational transmission of illness and evidence if illness modeling and/or reinforcement in IBS. However, the general amount of chronic illness in IBS families of origin has not been well documented to date.

Aims & Methods: We aimed to test whether the frequency of chronic medical problems in IBS families of origin is elevated and whether it is related to amount of IBS co-morbidities, associated with IBS morbidity and poorer current disease coping, and whether there is evidence of illness modeling. 530 IBS patients (Rome II or III criteria+ physician diagnosis; 79.4% females; mean age=35.8 years) and a sample of 337 demographically similar control subjects without gastrointestinal problems (78.7% females; mean age=34.7 years) reported whether they themselves, their mother, father or siblings had ever been diagnosed with 12 chronic medical conditions (in addition to IBS and psychiatric conditions) on the validated Co-morbid Medical Conditions Questionnaire – CMCQ. Subjects also completed the IBS Severity Scale Score (IBS-SSS), the IBS-QOL, the Visceral Sensitivity Index (VSI) and the Catastrophizing subscale of the Coping Strategies Inventory.

Results: IBS patients reported more medical conditions in their families than healthy subjects (Means: 2.86 vs. 1.39; p<.0001). Seven of the 12 medical conditions were more common in IBS families than control families (see Table). Amount of medical co-morbidities of IBS patients correlated robustly with co-morbidity amount in their mothers (Spearman’s Rho=0.42), fathers (Rho=0.25) and siblings (Rho=0.42); p < 0.0001 for all. These associations were also significant for male and female IBS patients analyzed separately. IBS patients also reported substantially higher rates of family IBS than controls: Overall 27.2% vs. 7.0%, Odds Ratio= 4.9; mothers 16.1% vs. 3.7%; fathers 6.9% vs. 1.3%; and siblings 13.8% vs. 2.6%; p < 0.0001 for all. The number of medical conditions in mothers and siblings of IBS patients was modestly but significantly correlated with more severe IBS (Rho = 0.15 and 0.20) and greater IBS-QOL impairment (Rho= -0.11 and -0.09) in the patients. VSI and Catastrophizing were unrelated to amount of family medical conditions.

Chronic medical diagnoses in families of IBS patients versus control subjects (*= p < 0.05):

	IBS families (%)	Control families (%)	Odds Ratio
Fibromyalgia	7.6*	3.0	2.64
Asthma	22.5	19.6	1.19
TMJ	14.8*	5.7	2.84
Chronic fatigue	5.3*	0.9	6.06
Migraines	38.3*	20.2	2.45
Tension Headaches	38.9*	18.5	2.81
Insomnia	27.9*	12.4	2.74
Back pain	32.7*	20.3	1.91
Chronic Pelvic Pain	3.2	1.2	2.60
Interstitial Cystitis	2.0	1.2	1.62
Prostatitis	5.3	3.0	1.79
Dysmenorrhea	5.5	2.7	2.08

Conclusion: IBS patients report an excess of chronic medical conditions in their immediate family compared to controls, and the illness amount in the family is correlated with patients' own co-morbidity load. No evidence of impact of family medical illness on maladaptive coping or visceral anxiety, nor of gender-specific modeling influences, were observed. Our findings need to be confirmed by surveying family members of IBS patients and controls directly about their medical history in future work. [Supported by grant RO1 DK31369]

Disclosure of Interest: None declared

P0430 SYSTEMATIC REVIEW WITH META-ANALYSIS: PREVALENCE OF BILE ACID MALABSORPTION IN IRRITABLE BOWEL SYNDROME WITH DIARRHOEA

S. Slattery¹, A. C. Ford², Q. Aziz¹, A. D. Farmer¹

¹Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine, London, ²Leeds Gastroenterology Institute, St. James’s University Hospital, Leeds, United Kingdom

Contact E-mail Address: a.farmer@qmul.ac.uk

Introduction: Irritable bowel syndrome is a prevalent disorder with a marked socioeconomic burden. Previous studies support the proposal that a subset of patients with features compatible with diarrhoea predominant IBS (IBS-D) have bile acid malabsorption (BAM).

Aims & Methods: The objective of this study was to perform a systematic review and meta-analysis to assess the prevalence of BAM in patients meeting accepted criteria for IBS-D. MEDLINE and EMBASE were searched up to February 2015. Studies recruiting adults with IBS-D, defined either by the Manning, Kruis, Rome I, II or III criteria and which used 23-seleno-25-homotaurocholic acid (SeHCAT) testing for the assessment of BAM were included. BAM was defined as 7 day SeHCAT retention of <10%. We calculated the rate of BAM and 95% confidence intervals (CI) using a random effects model. The methodological quality of included studies was evaluated using the Quality Assessment for Diagnostic Accuracy Studies (QUADAS-2).

Results: The search strategy identified 6 relevant studies comprising 908 individuals. The rate of BAM ranged from 16.9% to 35.3%, with an unadjusted rate [AF1] of 29.3%. The pooled rate was 28.1% (95% CI 22.6-34%). There was significant heterogeneity in effect sizes (Q-test χ² = 17.9, p<0.004; I² 72.1%). The type of diagnostic criteria used or study country did not significantly modify the effect.

Conclusion: These data provide evidence that in excess of one quarter of patients meeting accepted criteria for IBS-D have BAM. This distinction has implications for the interpretation of previous studies as well as contemporaneous clinical practice and future guideline development.

Disclosure of Interest: S. Slattery: None declared, A. Ford: None declared, Q. Aziz: None declared, A. Farmer Lecture fee(s): Almirall

P0431 UNSUPERVISED SYMPTOM-BASED CLUSTERING OF PATIENTS WITH IRRITABLE BOWEL SYNDROME (IBS)

A. Polster¹, S. M. P. Bennet¹, B. Le Nevé², H. Törnblom¹, L. Van Oudenhove³, L. Öhman¹, M. Simrén¹

¹University of Gothenburg, Göteborg, Sweden, ²Danone Nutricia Research, Palaiseau Cedex, France, ³University of Leuven, Leuven, Belgium

Contact E-mail Address: annikka.polster@gu.se

Introduction: Despite capacious research on IBS, the pathophysiology remains unclear and therapy options are sparse. Identifying subgroups of patients with a distinct profile may improve targeted research and development of individually tailored treatment options, as has been demonstrated in functional dyspepsia [1]

Aims & Methods: We included 164 patients with IBS defined by the Rome III criteria (mean age 34, range 18-62 years, 69% female). A crossvalidated Principal Component Analysis formed the basis for hierarchical clustering of patients based on symptom profiles. To model the symptom profile the following validated questionnaires were used: Gastrointestinal Symptom Rating Scale-IBS (GSRS-IBS) (individual items), bowel-related questions of the Rome III questionnaire, pain-related questions from the IBS Symptom Severity Score (IBS-SSS), and the average stool form during two weeks measured by the Bristol Stool Form Scale. An ANOVA with post-hoc t-tests (Bonferroni corrected) was applied to compare the clusters on the following measures: Pain intensity and pain thresholds measured by a rectal barostat procedure, oroanal transit time (radiopaque markers). Severity of anxiety and depression (Hospital Anxiety and Depression Scale (HAD), chronic fatigue (Fatigue Impact Scale (FIS), IBS-related quality of life (IBSQOL) and Sense of Coherence (SOC) were also compared between the clusters.

Results: The combination of symptom-based measurements was modelled with an optimized fit of three principal components, giving an R² of 0.4, regarded as a very robust model for patient data. Hierarchical clustering defined three major clusters: One group (16.5%) showed low severity scores for all modelled symptoms, two groups showed distinctly higher than average scores on either constipation (48.8%) or diarrhea (34.8%) measures. The two distinct-symptom groups showed significantly higher pain intensity and lower pain threshold measures, higher anxiety, depression and fatigue levels and lower scores for SOC and QOL when compared to the low-symptom IBS patients. The high constipation group also had significantly longer oroanal transit time than the other two, but the high diarrhea group did not differ from the low symptom group.

	Constipation group	Diarrhea group	Low symptoms group	Significance
Oroanal transit time	1.9 days^#	1.1 days*	1.0 days*	<0.0001
Pain intensity(VAS)	52 mm^	52 mm^	18 mm*#	<0.0001
Pain threshold	26 mmHg	26 mmHg^	31 mmHg#	0.05
Anxiety (HAD)	8	9^	6#	0.03
Depression (HAD)	5^	5	3*	0.03
FIS	65^	56^	31*#	0.001
SOC	131^	127^	150*#	0.01
QOL	59^	54^	79*#	<0.0001
GSRS Abd Pain	4.4^	4.7^	2.5*#	<0.0001
GSRS Bloating	4.9^	4.6^	3.2*#	<0.0001
GSRS Constipation	3.9^#	2.1^*	1.7*#	<0.0001
GSRS Diarrhea	3.2^#	5.1^*	2.5*#	<0.0001
GSRS Satiety	2.8^	2.9^	1.6*#	0.001

*vs Const, # vs Diarr, ^vs low symptoms

Conclusion: Symptom-based cluster analysis confirms previous grouping into constipation- and diarrhea-predominant groups, but also shows a low overall symptoms group, similar to what has been shown in functional dyspepsia [1]. This might reflect differences in pathophysiology and thus have impact on therapy strategies.

Disclosure of Interest: None declared

P0432 THE OVERLAP BETWEEN CONSTIPATION PREDOMINANT IRRITABLE BOWEL SYNDROME AND FUNCTIONAL CONSTIPATION IN PATIENTS ASSESSED FOR PELVIC FLOOR DISORDERS

M. Beer-Gabel¹, E. Bardan¹, D. Carter¹

¹Gastroenterology, Chaim Sheba Medical Center, Ramat Gan, Israel

Contact E-mail Address: dr.dancarter@gmail.com

Introduction: According to ROME III criteria, Pelvic floor symptoms (PFD) are incorporated into functional constipation, and strictly differed from constipation related IBS (c-IBS). However, abdominal pain was previously reported in patients reporting PFD

Aims & Methods: The aim of this study was to assess the incidence and type of IBS-related symptomatology on registration of those patients presenting with PFD and symptoms of chronic constipation.

Methods: All patients referred for the assessment and evaluation of PFD were analyzed by specific questionnaires including the Rome III criteria and the bowel component of the Birmingham Bowel and Urinary symptom questionnaire – BBUS-Q22 for IBS symptomatology. Patients were further assessed with dynamic transperineal ultrasonography or X-ray defecography, conventional station pull-through anorectal manometry and balloon expulsion test.

Results: Two hundred consecutive patients were included in the study (mean age 51.6 years, range 22-85 years).Reclassification of patients resulted in 167 patients (83.5%) being designated with IBS. Sixty six percent of patients reported regular improvement of symptoms with defecation with 55% noting symptoms associated with a change of stool form and 71% with fewer stools. There were significant differences noted in reporting of hard stools by those patients redesignated as IBS-PFD and a high percentage of reported soft stool in the FC-PFD patients. Repeated straining was more common in the IBS-PFD group as was fecal urgency, a sensation of defecation block and episodes of reported incomplete bowel emptying. The frequency of bowel movements between the groups was similar. There was no significant difference between the IBS-PFD and FC-PFD groups in the incidence of pelvic floor abnormalities. Anismus was diagnosed frequently in both groups, but was more prevalent in the IBS group (P=0.03).

Conclusion: The key outcome of this study is that PFD can be related to IBS as well as to FC. The reclassification of the majority of patients with PFD as also having significant IBS symptomatology might have important ramifications for eatment and functional outcome.

Disclosure of Interest: None declared

P0433 CO-MORBID FUNCTIONAL DYSPEPSIA IN IBS IS ASSOCIATED WITH AN INCREASED SYMPTOM RESPONSE TO A LACTULOSE NUTRIENT CHALLENGE TEST

D. Pohl¹, L. van Oudenhove², H. Törnblom³, B. Le Nevé⁴, J. Tack², M. Simren³

¹Gastroenterology, University Hospital Zurich, Zurich, Switzerland, ²TARGID, University of Leuven, Leuven, Belgium, ³Internal Medicine, University of Gothenburg, Gothenburg, Sweden, ⁴Danone Nutricia Research, Palaiseau Cedex, France

Contact E-mail Address: daniel.pohl@usz.ch

Introduction: Irritable Bowel Syndrome (IBS) is associated with an increased postprandial symptom response to a 25g combined lactulose nutrient challenge test compared to healthy controls (1). Co-morbid Functional Dyspepsia (FD) is highly prevalent in IBS, but is not regularly taken into account. Our aim was to investigate the relationship between co-morbid FD status and the time course of the postprandial symptom response to this test.

Aims & Methods: 205 IBS patients (Rome III), 94 (46%) of whom had co-morbid FD (Rome III), and 83 healthy volunteers (HV) consumed a 400-ml liquid breakfast (Nutridrink, 1.5 kcal/ml, 16% proteins, 49% carbohydrates, 35% fat, gluten free, lactose <0.025 g/100 ml) combined with 25g of lactulose after an overnight fast. They completed graded rating scales (0-20) assessing severity of five gastrointestinal (GI) symptoms (abdominal pain, bloating, nausea, gas, urgency) and overall “digestive comfort” before breakfast and every 15 minutes up to 240 minutes postprandially. The relationship between subject status (HV, IBS, IBS + FD) and the course of GI symptom scores over time was analyzed using linear mixed models. “Time” was included as a categorical within-subject effect, “group” (HV, IBS, IBS + FD) was included as categorical between-subject effect, and the group-by-time interaction effect was also included. The main effect of group and the interaction effect are the effects of interest.

Results: A significant main effect of group, indicating a significant difference between the three groups in the average symptom level over time, was found for all symptoms (all p<.0001). Post-hoc tests showed significant differences for all pairwise comparisons between the three groups (all p<.05, stepdown Bonferroni corrected), including the IBS versus IBS + FD comparison. A group-by-time interaction effect was found for pain (p=.002), bloating (p=.0008), urgency (p=0.019), and digestive comfort (p=.002), but not for gas (p=.07) or nausea (p=.52). Planned comparisons on the significant interaction effects showed that in HV, contrary to IBS and IBS + FD, no postprandial increase in ratings was found for any of the symptoms, resulting in significant differences at all time points (all p<.0001, stepdown Bonferroni corrected) between HV on one hand and both IBS and IBS + FD on the other hand. Differences between IBS and IBS + FD were found at all time points for pain and digestive comfort (all p<.001 and p<.05, stepdown Bonferroni corrected, respectively), up to 2 hours postprandially for bloating (all p<.05, stepdown Bonferroni corrected) and at 30 minutes postprandially only for urgency (p=.005, stepdown Bonferroni corrected).

Conclusion: In IBS, co-morbid FD is associated with increased GI symptom reporting, both preprandially and after a combined lactulose nutrient challenge test, particularly for the symptoms pain, bloating, urgency, and is associated with decreased overall digestive comfort reporting. These results indicate that presence of co-morbid FD is relevant for symptom reporting in IBS.

Disclosure of Interest: D. Pohl Lecture fee(s): Almirall, Sucampo, Takeda, Consultancy: Almirall, Astra Zeneca, L. van Oudenhove: None declared, H. Törnblom Lecture fee(s): Almirall, Shire, Consultancy: Almirall, B. Le Nevé Conflict with: Danone Research Employee, J. Tack Financial support for research: Abbott, Almirall, AstraZeneca, Janssen, Menarini, Novartis, Shire, Takeda, Zeria, Lecture fee(s): Almirall, AstraZeneca, Janssen, Menarini, Shire, Zeiria, Consultancy: AlfaWassermann, Almirall, AstraZeneca, Danone, GI Dynamics, GlaxoSmithKline, Ironwood, Janssen, Menarini, Novartis, Rhythm, Shire, Sucampo, Takeda, Theravance, Tsumura, Yuhan, Zeria, M. Simren Financial support for research: Danone Research, Lecture fee(s): Almirall, Shire, Tillotts, Takeda, Consultancy: AstraZeneca, Almirall, Shire, Danone Research, Nestlé, Chr Hansen

P0434 DIAGNOSIS AND MANAGEMENT OF MODERATE-TO-SEVERE IRRITABLE BOWEL SYNDROME WITH CONSTIPATION (IBS-C) IN EUROPE: POOLED RESULTS FROM THE IBIS-C STUDY

J. Tack¹, V. Stanghellini², F. Mearin³, Y. Yannakou⁴, P. Layer⁵, B. Coffin⁶, M. Simren⁷, J. Mackinnon⁸, J. Bertsch⁸, J. Fortea⁹

¹University Hospital Gasthuisberg, Leuven, Belgium, ²University of Bologna, Bologna, Italy, ³Centro Médico Teknon, Barcelona, Spain, ⁴University Hospital of North Durham, Durham, United Kingdom, ⁵Israelitic Hospital, Hamburg, Hamburg, Germany, ⁶Louis-Mourier Hospital, Colombes, France, ⁷Sahlgrenska University Hospital, Göteborg, Sweden, ⁸TFS Develop S.L., Barcelona, Spain, ⁹Almirall S.A., Barcelona, Spain

Contact E-mail Address: cristina.ceballos@tfscro.com

Introduction: This is the first study to assess the diagnostic and therapeutic management of moderate-to-severe IBS-C in six European countries (France, Germany, Italy, Spain, Sweden and UK). Here we present the pooled results from all participating countries.

Aims & Methods: Observational study in patients diagnosed with IBS-C (Rome-III criteria) in the last five years and moderate-to-severe disease severity at inclusion (IBS-Symptom Severity Scale [IBS-SSS] score ≥175), with a 12-month follow-up (6 months retrospective and 6 months prospective), in order to assess healthcare resource utilisation (HRU) and costs prior to and after an active phase of the disease. Diagnostic procedures were collected since the onset of symptoms. The study began in April 2012; last patient last visit: January 2014.

Results: 525 patients were included (60% severe, mean age [±SD] 45.3 ± 15.8 years old, 86.9% female). Mean time since diagnosis: 3.0 ± 5.2 years; mean symptom duration: 12.8 ± 13.1 years. Diagnostic procedures since the onset of symptoms were highly variable: the most common were blood tests (71.6%; range: 88.9% Sweden– 57.6% France); colonoscopy (62.9%; range: 78.4% Germany–41.1% Italy); abdominal ultrasound (54.7%; 62.7% Germany–36.1% Sweden). The main associated comorbidities were anxiety (34.1%), dyspepsia (31.0%), headache (28.0%), and insomnia (27.0%). 62.1% (74.1% Italy–57.6% France) of patients had an average of 4.0 ± 2.7 diagnostic tests (4.5 ± 3.0 Italy–3.4 ± 2.7 France) during follow-up and 65.3% took prescription drugs for their IBS-C (90.4% UK–41.1% Italy). The most commonly prescribed medications were laxatives (48.8%), antispasmodics (19.8%), and prokinetics (18.9%). 20.4% took other medications. Specifically, laxatives were prescribed as a monotherapy (14.1%), in combination with antispasmodics (6.3%) or with another drug that was not an antispasmodic, antidepressant, or prokinetic (10.7%). Overall, 67.2% of patients took non-prescription medication for their IBS-C (82.1% Italy–56.3% Spain) (33.0% laxatives; 24.2% pre/probiotics, 19.6% herbal medicine) and 33.0% of patients sought complementary therapies (44.4% Sweden–27.5% Germany). Overall, marginal improvement was noted in symptom severity (IBS-SSS total score ± SD) between baseline (323.2 ± 84.3) and the 6-month visit (253.9 ± 105.6, 76.1% moderate-to-severe; 85.4% France–67.3% Italy).

Conclusion: IBS-C symptoms remain undiagnosed for an average of almost 10 years and there is a high degree of variability in diagnostic and management procedures between European countries. Over half of the patients continued to undergo diagnostic tests after a diagnosis has been reached and the degree of control did not improve over time despite a high level of prescription and non-prescription medication use. At the end of the study over three quarters of patients still suffered from moderate-to-severe IBS-C.

Disclosure of Interest: J. Tack Conflict with: Grants / research support: Abbott, Novartis, Shire. Honoraria / consultancy fees: Almirall, AstraZeneca, Danone, GI Dyamics, GlaxoSmithKline, Ironwood, Janssen, Menarini, Novartis, Rhythm, Shire, Takeda, Theravance, Tsumura, Will Pharma, Zeria. Speaker fees: Abbott, Almirall, AstraZeneca, Janssen, Menarini, Novartis, Shire, Takeda, Zeria., V. Stanghellini Conflict with: Grants / research support: Alfa Wassermann, Almirall, Aptalis, Italchimici, Norgine, Shire, Takeda, Valeas. Honoraria / consultancy fees: Abbott, Alfa Wasserman, Almirall, Angelini, Aptalis, CM&D Pharma, Farmaderma, Ironwood, Norgine, Shire, Takeda, Valeas, Vibrant, Zeria., F. Mearin Conflict with: Speaker fees: Almirall., Y. Yannakou Conflict with: Grants: Shire; Medtronic. Speaker fees: Almirall; Shire; Sucampo., P. Layer Conflict with: Abbott / Solvay, Almirall, Aptalis / Axcan, Norgine, Shire., B. Coffin Conflict with: Honoraria / consultancy fees: Almirall, Mundipharma, Mayoly Spindler, Menarini., M. Simren Conflict with: Unrestricted research grants: Danone, AstraZeneca. Consultant/Advisory Board member: Danone, Nestlé, Chr Hansen, Almirall, Albireo, Shire. Participation in a company-sponsored speaker’s bureau: Almirall, Shire, Tillotts, Takeda., J. Mackinnon Conflict with: Employee of TFS Develop S.L, contracted by Almirall S.A to conduct the study., J. Bertsch Conflict with: Employee of TFS Develop S.L, contracted by Almirall S.A to conduct the study, J. Fortea Conflict with: Employee of Almirall, S.A

P0435 CLASSIFICATION OF IRRITABLE BOWEL SYNDROME – A CRITICAL EXPLORATION OF THE ROME III CRITERIA

K.-A. Wensaas¹, K. Hanevik², T. Hausken², G. E. Eide³, N. Langeland², K. Mørch³, G. Rortveit⁴

¹Research Unit for General Practice, Uni Research Health, ²University of Bergen, ³Haukeland University Hospital, ⁴Uni Research Health, Bergen, Norway

Contact E-mail Address: knut-arne.wensaas@uni.no

Introduction: The aims of this study is to explore the subtypes of irritable bowel syndrome (IBS) in a cohort three years after acute Giardia infection and in a control group with sporadic IBS. Further, to compare these subtypes according to Rome III criteria (based on stool consistency) to a classification based on stool frequency (diarrhoea or constipation).

Aims & Methods: Prospective cohort study of patients aged ≥18 years with confirmed giardiasis during a large outbreak in Bergen, Norway, in 2004 and a group of controls matched by age and gender. A postal questionnaire was mailed to all participants in 2007, three years after the acute infection. Outcomes were IBS according to Rome III criteria, and diarrhoea (defined as ≥4 bowel movements a day at least “sometimes”) and constipation (defined as <3 defecations at least “sometimes”).

Results: Response rates were 66% (781/1184) among exposed patients and 33% (1099/3380) among controls. The prevalence of IBS was 47% (346/781) and 14% (154/1095) respectively, with an adjusted relative risk 3.3 (95% CI 2.9 to 3.7). In the Giardia group the distribution of IBS based on stool consistency according to Rome III criteria was 38% IBS-D, 46% IBS-M, 10% IBS-C and 6% IBS-U, and in the control group 32% IBS-D, 34% IBS-M, 19% IBS-C and 14% IBS-U.

Of the IBS patients in the Giardia group 70% reported diarrhoea and 14% reported constipation, compared to 46% and 24%, respectively, in the control group. Subtyping IBS based on these characteristics yielded a different distribution than when subtyping based on stool consistency (p < 0.001 in both groups, Kappa-values 0.168 and 0.279). In the Giardia group 62% had IBS and diarrhoea, 7% had IBS and constipation and 7% had IBS and both, the corresponding numbers in the control group was 40%, 18% and 6%.

Table.

Relationship between IBS subtyped according to Rome III criteria (based on stool consistency) and IBS subtyped by frequency of bowel movements (diarrhoea/constipation at least “sometimes”) among exposed and controls three years after acute giardiasis.

		IBS with diarrhoea	IBS with constipation	IBS with diarrhoea and constipation	IBS without diarrhoea nor constipation	Total
Exposed	IBS-D	102	3	5	22	132 (38%)
	IBS-C	17	12	5	19	34 (10%)
	IBS-M	98	8	15	38	159 (46%)
	IBS-U	1	7	0	13	21 (6%)
Total	215 (62%)	24 (7%)	25 (7%)	82 (24%)	346 (100%)
Control	IBS-D	35	1	1	13	50 (32%)
	IBS-C	9	11	0	10	30 (19%)
	IBS-M	14	13	8	18	53 (34%)
	IBS-U	4	2	0	15	21 (14%)
Total	62 (40%)	27 (18%)	9 (6%)	56 (36%)	154 (100%)

Conclusion: In post-giardiasis IBS there was a larger proportion of IBS-D and IBS-M compared to sporadic IBS in the controls. Subtyping IBS based on diarrhoea and constipation, rather than on stool consistency according to Rome criteria, significantly changed how patients were classified, and the resulting changes appeared to be different in post giardiasis IBS compared to sporadic IBS. These results challenge the accuracy of the current Rome III criteria in characterizing IBS.

Disclosure of Interest: None declared

P0436 SERUM AND MUCOSAL CYTOKINE PROFILES DO NOT DISCRIMINATE BETWEEN HEALTH AND IBS, BUT INCREASED LEVELS OF PRO-INFLAMMATORY CYTOKINES CORRELATE WITH LONGER OROANAL TRANSIT TIME AND REDUCED PSYCHOLOGICAL WELL-BEING

S. M. P. Bennet¹², A. Polster¹, H. Törnblom¹, S. Isaksson¹², B. Le Nevé³, M. Simrén¹, L. Öhman¹²

¹Internal Medicine and Clinical Nutrition, ²Microbiology and Immunology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, ³Life Science, Danone Nutricia Research, Palaiseau, France

Contact E-mail Address: magnus.simren@medicine.gu.se

Introduction: Evidence suggests patients with irritable bowel syndrome (IBS) have an altered cytokine profile, although it is unclear if cytokines are associated with severity of symptoms. We therefore aimed to determine if global cytokine profiles differ between IBS and healthy and if cytokine expression is associated with IBS symptoms.

Aims & Methods: Serum from 144 IBS patients and 42 healthy subjects was analyzed for cytokine levels (IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IFN-γ, TNF) by MSD MULTI-ARRAY analysis. Sigmoid colon biopsies from 109 IBS and 36 healthy were analyzed for mRNA expression (IL-8, IL-10, TNF, FOXP3) by qRT-PCR. Global cytokine profile of serum and mucosal cytokines was evaluated by multivariate analysis (SIMCA-P+ software). Study subjects underwent rectal sensitivity test using a barostat, and oroanal transit assessment using radiopaque markers. IBS symptom severity and psychological symptoms were assessed using Patient Health Questionnaire-15, IBS Severity Scoring System and Hospital Anxiety and Depression scale.

Results: According to multivariate discrimination analysis, global cytokine profiles of IBS patients and healthy subjects overlapped, thus not able to discriminate IBS patients from healthy. However, serum levels of pro-inflammatory cytokines IL-6 and IL-8 tended to be increased, and IFN-γ tended to be decreased in IBS patients. Mucosal mRNA expression of IL-10 and FOXP3 tended to be lower in IBS patients (Table 1). Other measured serum and mucosal cytokines did not differ between IBS and healthy subjects. Subjects (including IBS and healthy) with longer oroanal transit had increased mucosal mRNA expression of IL-8 (r = 0.33; p = < 0.0001) and TNF (r = 0.2; p = 0.02). No correlation of rectal pain threshold and cytokine expression was recorded. Subjects with a higher degree of somatization tended to have increased serum levels of IL-6 (r = 0.2; p = 0.01), IL-8 (r = 0.18; p = 0.01) and TNF (r = 0.15; p = 0.04). Subjects reporting more anxiety tended to have lower mucosal mRNA expression of IL-10 (r = -0.16; p = 0.05). Subjects reporting higher levels of depression had increased serum levels of IFN-γ (r = 0.18; p = 0.01) and IL-6 (r = 0.15; p = 0.04). IBS symptom severity tended to correlate positively with serum levels of IL-6 in IBS patients (r = 0.17; p = 0.05).

Abstract number: P0436 Table 1.

Serum cytokines and mucosal mRNA expression in healthy controls and IBS patients.

Serumcytokine(pg/ml)	IBS(n=144)	Healthy(n=42)	p-value†
IL-6	0.4 (0.28-0.68)	0.34 (0.24-0.54)	0.06
IL-8	11.3 (7.51-14.41)	9.1 (6.49-13.15)	0.12
IFN-γ	8.0 (5.1-12.1)	10.9 (6-15.3)	0.07
Mucosalcytokine(2ΔCt)	IBS(n=109)	Healthy(n=36)	p-value†
IL-10	8.6x10−5 (6.9x10−5-1.1x10−4)	9.6x10−5 (7.8x10−5-1.3x10−4)	0.05
FOXP3	2.5x10−4 (1.8x10−4-3.5x10−4)	3.1x10−4 (2.2x10−4-3.7x10−4)	0.07

†Mann Whitney U test. Data shown as median (25%>75%)

Conclusion: Global cytokine profiles were similar between IBS patients and healthy subjects, thus cytokine profiles do not discriminate between IBS and health. Nonetheless, increased levels of pro-inflammatory cytokines were associated with longer oroanal transit and reduced psychological wellbeing in IBS and healthy subjects.

Disclosure of Interest: None declared

P0437 AN APPRAISAL OF CLINICAL PRACTICE GUIDELINES FOR IRRITABLE BOWEL SYNDROME

Y. Gou¹, F. Li², W. Wang¹, A. Jin¹, Y. Zhao³, X. Huang¹

¹Digestive Department, ²Clinical Laboratory, ³ Key Laboratory of Digestive System Tumors of Gansu Province, The Second Hospital of Lanzhou University, Lanzhou, China

Contact E-mail Address: huangxiaojunlzu@163.com

Introduction: Irritable bowel syndrome(IBS) is a chronic gastrointestinal disorder with an estimated prevalence of 10-20%. Many countries lack appropriate clinical practice guidelines for the diagnosis and treatment of IBS. It can be painful and debilitating, lead to feelings of anxiety and depression, and negatively affect quality of life.

Aims & Methods: To determine and assess the quality of clinical practice guidelines on IBS. Four databases (included MEDLINE and EMBASE) and some guideline websites were searched till to March 2015. Methodological quality of selected guidelines was assessed by the AGREE II instrument.

Results: From 863 citations, 17 relevant guidelines were included. The overall agreement among reviewers was moderate (Intra-class correlation coefficient=0.81; 95% confidence interval [CI], 0.56-0.76). Overall, the guidelines performed well in the clarity and presentation domain with a mean score of 56.12%, followed by scope and purpose (58.56%) and rigor of development (50.25%). In contrast, poor scores were given for the remaining domains: stakeholder involvement (23.25%), applicability (28.14%) and editorial independence (31.54%). Four sixths domains scores were lower when compared with international level. There are 5 (22.73%) guidelines described the systematic methods for searching. And only 5 (23.81%) guidelines reported methodological expertise were included in guideline developing teams.

Conclusion: Although existing guidelines may accurately reflect agreed clinical practice, many guidelines lack proper methodological quality. Greater efforts are needed to provide high-quality guidelines that serve as a useful and reliable tool for clinical decision-making in this field.

Disclosure of Interest: None declared

P0438 EFFECTS OF ELUXADOLINE ON ABDOMINAL PAIN IN PATIENTS WITH IRRITABLE BOWEL SYNDROME WITH DIARRHOEA: RESULTS OF TWO PHASE 3 TRIALS

A. J. Lembo¹, L. S. Dove², D. A. Andrae³, L. Turner², J. M. Davenport², P. S. Covington²

¹Harvard Medical School, Boston, ²Furiex Pharmaceuticals, Inc., an affiliate of Actavis, Inc., ³Actavis Inc., Jersey City, United States

Contact E-mail Address: alembo@bidmc.harvard.edu

Introduction: Eluxadoline (ELX) is a locally active, mixed mu-opioid receptor agonist and delta-opioid receptor antagonist that demonstrated improvements in the symptoms of irritable bowel syndrome with diarrhoea (IBS-D) in two Phase 3 trials.

Aims & Methods: To examine the efficacy of ELX in abdominal pain in IBS-D, additional prospective analyses were performed for two double-blind, placebo (PBO)-controlled Phase 3 trials (IBS-3001, IBS-3002). Patients (pts) meeting Rome III criteria for IBS-D were randomised to twice-daily ELX (75 or 100 mg) or PBO. Both trials had identical designs through 26 weeks (wks) of treatment. The primary endpoint was a composite response based on simultaneous daily improvement in worst abdominal pain (WAP) and stool consistency over Wks 1–12 (US Food and Drug Administration [FDA] endpoint) and Wks 1–26 (European Medicines Agency [EMA] endpoint). Additional prospective analyses of WAP (0–10 scale) included: Cochran–Mantel–Haenszel (CMH) assessments of WAP responders, defined as pts with ≥50% of days with ≥30% improvement (study level and pooled); longitudinal analyses (LA) of WAP response rates, both at specific time points and at the study level; assessment of pooled data using CMH analyses of WAP responders over the two intervals based on ≥40% and ≥50% improvements in pain; and an analysis of covariance (ANCOVA) assessment of change from baseline (CFB) in WAP daily scores of pooled data at specific time points.

Results: A total of 2428 pts with IBS-D were enrolled across both trials. A significantly greater proportion of ELX-treated pts (75 or 100 mg) were FDA and EMA composite endpoint responders compared with pts who received PBO (p < 0.05), with the exception of ELX 75 mg in IBS-3001 over Wks 1–26. CMH analyses of the pooled data showed no significant differences for WAP responders (ie ≥30% pain improvement for ≥50% of days; Table 1) between ELX-treated pts and those who received PBO. Significant differences were observed for ELX 100 mg over PBO for WAP responders at both the ≥40% and ≥50% pain improvement levels. Findings were similar for the pooled data ANCOVA CFB in WAP scores at Wks 12 and 26. At the study level, LA of WAP daily response rates showed significant improvement with ELX 75 mg vs PBO at Wk 26 in IBS-3001 (p=0.016), and significant improvements for both ELX doses at Wks 12 and 26 in IBS-3002 (p ≤ 0.013).

Table 1: Pooled WAP analyses

	Wks 1–12			Wks 1–26
	PBO	ELX 75 mg	ELX 100 mg	PBO	ELX 75 mg	ELX 100 mg
≥30% WAP improvement*	42.3	45.00.261	46.80.069	44.0	46.30.357	48.30.086
≥40% WAP improvement*	35.8	40.10.078	43.20.003	37.7	41.50.122	44.20.008
≥50% WAP improvement*	30.0	34.70.047	36.00.011	32.5	36.40.101	38.70.009
CFB in WAP**	-2.6	-2.80.060	-3.0<0.001	-3.0	-3.30.023	-3.40.002

*Percent responders and p values compared with PBO

**CFB in WAP score and p value compared with PBO

Conclusion: Phase 3 trial findings demonstrated that ELX improves abdominal pain in pts with IBS-D, particularly for ELX 100 mg with ≥40% and ≥50% pain improvement definition for responders. This was further supported by LA of WAP daily response rates and ANCOVA CFB in WAP score analyses.

Disclosure of Interest: A. Lembo Consultancy: Forest Laboratories (now Actavis, Inc.), Salix Pharmaceuticals and Prometheus, L. Dove Financial support for research: Actavis, Furiex Pharmaceuticals (subsidiary), Shareholder: Actavis, Furiex Pharmaceuticals (subsidiary), D. Andrae Financial support for research: Actavis, Furiex Pharmaceuticals (subsidiary), Shareholder: Actavis, Furiex Pharmaceuticals (subsidiary), L. Turner Financial support for research: Actavis, Furiex Pharmaceuticals (subsidiary), Shareholder: Actavis, Furiex Pharmaceuticals (subsidiary), J. Davenport Financial support for research: Actavis, Furiex Pharmaceuticals (subsidiary), Shareholder: Actavis, Furiex Pharmaceuticals (subsidiary), P. Covington Consultancy: Actavis, Shareholder: Furiex Pharmaceuticals (subsidiary)

P0439 ROBUSTNESS OF ELUXADOLINE FOR THE TREATMENT OF IRRITABLE BOWEL SYNDROME WITH DIARRHOEA: RESULTS FROM PHASE 3 COMPOSITE ENDPOINT ASSESSMENTS

B. E. Lacy¹, L. S. Dove², D. A. Andrae³, J. M. Davenport², L. Turner², R. Lopez², P. S. Covington²

¹Geisel School of Medicine at Dartmouth, Hanover, ²Furiex Pharmaceuticals, Inc., an affiliate of Actavis, Inc., ³Actavis, Inc, Jersey City, United States

Contact E-mail Address: Brian.E.Lacy@hitchcock.org

Introduction: Eluxadoline (ELX), a locally active, mixed mu-opioid receptor agonist and delta-opioid receptor antagonist, has been shown to treat symptoms of irritable bowel syndrome with diarrhoea (IBS-D).

Aims & Methods: The robustness of ELX treatment was assessed by comparing the results of four composite efficacy endpoints across two double-blind, placebo (PBO)-controlled Phase 3 trials (IBS-3001, IBS-3002). Patients (pts) meeting Rome III criteria for IBS-D were randomised to twice-daily ELX (75 or 100 mg) or PBO. Efficacy was evaluated through 26 weeks (wks). Pts rated worst abdominal pain (WAP; 0–10 scale) and stool consistency (Bristol Stool Scale [BSS]) daily. The primary efficacy endpoint was a composite response (based on simultaneous daily improvement in WAP and stool consistency, with ≥50% of days demonstrating a response) evaluated over Wks 1–12 (Food and Drug Administration; with ≥60/84 days of diary compliance) and Wks 1–26 (European Medicines Agency; with ≥110/182 days of diary compliance). Other prospectively defined composite endpoints included: a worst case approach, using the same daily criteria but requiring an absolute ≥42/84 days or ≥91/182 days of response, respectively, regardless of diary compliance; weekly (wkly) Method 1, requiring a wkly average BSS of ≤5 if baseline average BSS ≥6, or a reduction in wkly average BSS scores of ≥1 point for pts with a baseline average BSS ≥5.5 and <6; wkly Method 2, requiring a ≥50% decrease in the number of days in a week when BSS was ≥6 compared with the number of days at baseline (Wk 1) when the BSS was ≥6. Both wkly methods used the same WAP criteria, ie ≥30% improvement in the wkly average of WAP scores compared with average baseline pain. Both wkly methods required improvement of WAP and BSS in the same wk for ≥6/12 wks for a pt to be considered a responder.

Results: A total of 2428 pts with IBS-D were enrolled across both trials. In general, significantly more pts receiving ELX were composite responders than those receiving PBO, regardless of the composite endpoint analysed (p < 0.05; Table 1). Comparable results for composite endpoints were seen for both ELX dose groups, although results for the 75 mg group were slightly less robust than for the 100 mg group at the study level. Data from pooled analyses showed similar findings.

Abstract number: P0439 Table 1.

Prospective study-specific results

Responders (%)p value vs PBO		IBS-3001			IBS-3002
PBO	ELX 75 mg	ELX 100 mg	PBO	ELX 75 mg	ELX 100 mg
Daily composite endpoint Primary efficacy	Wks 1–12	17.1	23.90.014	25.1 0.004	16.2	28.9<0.001	29.6<0.001
Wks 1–26	19.0	23.40.112	29.3<0.001	20.2	30.40.001	32.7<0.001
Daily composite endpoint Worst case	Wks 1–12	16.6	23.40.013	24.20.006	13.9	28.3<0.001	28.3 <0.001
Wks 1–26	15.9	22.70.012	26.3<0.001	15.7	28.9<0.001	30.6<0.001
Wkly composite endpoint Method 1	Wks 1–12	25.8	33.50.013	36.20.001	26.4	36.20.004	37.7<0.001
Wkly composite endpoint Method 2	Wks 1–12	31.1	38.40.026	41.8 0.001	32.7	38.60.091	45.0<0.001

Conclusion: Results from two Phase 3 trials demonstrate that ELX is an effective treatment for IBS-D based on robust results across multiple composite endpoints and across time.

Disclosure of Interest: B. Lacy Financial support for research: Participated in scientific advisory boards for Ironwood, Prometheus, Salix, and Forest (now Actavis, Inc.), L. Dove Financial support for research: Actavis, Furiex Pharmaceuticals (subsidiary), Shareholder: Actavis, Furiex Pharmaceuticals (subsidiary), D. Andrae Financial support for research: Actavis, Furiex Pharmaceuticals (subsidiary), Shareholder: Actavis, Furiex Pharmaceuticals (subsidiary), J. M. Davenport Financial support for research: Actavis, Furiex Pharmaceuticals (subsidiary), Shareholder: Actavis, Furiex Pharmaceuticals (subsidiary), L. Turner Financial support for research: Actavis, Furiex Pharmaceuticals (subsidiary), Shareholder: Actavis, Furiex Pharmaceuticals (subsidiary), R. Lopez Financial support for research: Actavis, Furiex Pharmaceuticals (subsidiary), Shareholder: Actavis, Furiex Pharmaceuticals (subsidiary), P. Covington Consultancy: Actavis, Shareholder: Furiex Pharmaceuticals (subsidiary)

P0440 ADDITION OF GLUCOSE TO FRUCTOSE REDUCES BREATH HYDROGEN BUT NOT SYMPTOMS IN FRUCTOSE MALABSORBERS WITH A FUNCTIONAL BOWEL DISORDER

C. Tuck¹, L. Ross¹, J. Muir¹, J. Barrett¹, P. Gibson¹

¹Department of Gastroenterology, Monash University, Prahran, Australia

Contact E-mail Address: caroline.tuck@monash.edu

Introduction: Absorption of fructose is enhanced by the addition of equal amounts of glucose in healthy volunteers. The success of this strategy in improving absorption of fructose and in reducing abdominal symptoms when consuming free fructose or fructans in patients with functional bowel disorders is not known. This study aimed to address these issues by performing a randomised, double blind, cross-over trial.

Aims & Methods: Breath hydrogen and symptom response to six sugar solutions - glucose; sucrose; fructose; fructose + glucose; fructo-oligosaccharide (FOS); FOS + glucose – given in random order were assessed in patients with fructose malabsorption and a functional bowel disorder (Rome III). Following a 24 hour run-in period where participants consumed a diet low in fermentable carbohydrates (fibre and FODMAPs), participants collected breath samples at baseline and every 20 minutes for 4 h after consuming the sugar solution. A further 8 breath samples were collected hourly, during which only food low in FODMAPs was consumed. Breath hydrogen was calculated as area-under-the-curve. Symptom scores were recorded at the end of each day, using both 100 mm visual analogue scale and 4-point Likert scale.

Results: Of the 26 participants (3 female, aged 22-65 y), 21 had IBS, 3 functional bloating, 1 functional diarrhoea and 1 chronic constipation. Breath hydrogen response to 25 g fructose (775 ± 904 ppm.4 h (mean ± SD)) reduced during the first 4 h following the addition of 25 g glucose (84 ± 99; p=0.012, t-test), which was similar to that after glucose alone (133 ± 175) or sucrose (155 ± 224). Breath hydrogen response to 10g FOS (3089 ± 1688) was not changed with the addition of glucose (2166 ± 1320; p=0.559). Overall abdominal symptoms after fructose (median 15 mm, IQR 2-46) or FOS (19.2-32) were not changed with the addition of glucose (5.1-35; p=0.236; 17.2-46, p=0.926, respectively). Addition of glucose worsened abdominal pain when given with FOS (5.1-16 vs 13.2-18; p=0.049) and nausea when given with fructose (1.0-2 vs 2.1-10; p=0.018). When assessed by the Likert scale, addition of glucose to fructose increased nausea (p=0.011) and to FOS increased nausea (p=0.011) and wind (p=0.027).

Conclusion: The results do not support the strategy of adding glucose to foods high in free fructose to reduce fructose malabsorption or to fructans as it does not reduce, and potentially worsens symptoms associated with consumption of these sugars in patients with functional bowel disorders.

Disclosure of Interest: None declared

P0441 TRANS-ANAL IRRIGATION THERAPY TO TREAT ADULT CHRONIC FUNCTIONAL CONSTIPATION: A SYSTEMATIC REVIEW

C. Emmett¹², H. Close², J. Mason², Y. Yiannakou¹²

¹University Hospital of North Durham, ²Durham University, Durham, United Kingdom

Contact E-mail Address: Christopher.Emmett@nhs.net

Introduction: Trans-anal irrigation (TAI) is used widely to treat bowel dysfunction, although evidence for its use in adult chronic functional constipation remains unclear. Long-term outcome data are lacking, and the effectiveness of therapy in this patient group is not definitively known¹.

Aims & Methods: Evidence for effectiveness and safety was reviewed and the quality of studies was assessed. Primary research articles of patients with chronic functional constipation, treated with TAI as outpatients and published in English in indexed journals were eligible. Searching included major bibliographical databases and search terms: bowel dysfunction, defecation, constipation and irrigation. Fixed- and random-effect meta-analyses were performed.

Results: Seven eligible uncontrolled studies^1-7, including 243 patients, of retrospective or prospective design were identified. The definition of treatment response varied and was Investigator-determined. The fixed-effect pooled response rate was 50.4% (95%CI: 44.3% to 56.5%) but featured substantial heterogeneity (I²=67.1%). A random-effects estimate was similar: 50.9% (95%CI: 39.4% to 62.3%). Adverse events were inconsistently reported but were commonplace and minor.

Conclusion: The reported success rate of TAI is about 50%, which may be adequate for chronic constipation. Findings may vary between studies due to methodological or contextual differences. Evidence for TAI in functional constipation is weak: there is a need for well-designed prospective trials to evaluate the effectiveness of treatment.

Disclosure of Interest: None declared

P0442 IN VITRO STUDIES ON THE ANTI-SPASMODIC AND ANTI-INFLAMMATORY POTENTIAL OF CHAMOMILE, MYRRH AND COFFEE CHARCOAL – COMPONENTS OF A TRADITIONAL HERBAL MEDICINAL PRODUCT (MYRRHINIL-INTEST®)

C. Vissiennon¹², K.-H. Goos³, O. Goos³, J. Arnhold¹, K. Nieber²

¹Institue of Medical Physics and Biophysics, Medical Faculty, ²Institute of Pharmacy, University of Leipzig, Leipzig, ³Repha GmbH Biologische Arzneimittel, Langenhagen, Germany

Contact E-mail Address: cica.vissiennon@uni-leipzig.de

Introduction: The herbal medicinal product Myrrhinil-Intest^® consisting of myrrh, chamomile flower dry extract and coffee charcoal is marketed in Germany since 1959. Clinical data prove the effectiveness of this herbal preparation for inflammatory intestinal disorders such as irritable bowel syndrome, functional diarrhea as well as inflammatory bowel disease (colitis ulcerosa) [1,2]. However, the underlying pharmacological mechanisms within the gastrointestinal system have not yet been fully elucidated.

Aims & Methods: Objective of this study was to assay the herbal components for their effect on intestinal motility and inflammation. Thus, spasmolytic activity was determined using isometric tension measurement in isolated rat small intestinal preparations. An in vitro TNBS inflammation model in rat small intestinal preparations was used to determine anti-inflammatory activity. Therefore, the effect of the plant extracts on TNBS induced inflammatory damage was characterised based on TNFα-gene expression analysis, isometric contraction measurement and histological analysis. Furthermore, TNFα release from LPS-stimulated THP-1 cells was assayed. Additionally, microarray gene expression analysis was performed in LPS/IFNγ stimulated native human macrophages to determine underlying mechanisms.

Results: Chamomile flower (KA) and ethanolic myrrh extract (MY) exerted a spasmolytic effect by inhibiting the acetylcholine-induced contractions to 56% (KA: IC50 = 160 μg/ml) and 10% (MY: IC50 = 158 μg/ml) respectively. Serial testing with increasing concentration of the calcium-channel agonist (BAY K8644, 10⁻¹⁰–10⁻⁷ M) in the presence of different MY concentrations (0.15 - 0.35 mg/ml) demonstrated that MY acts via inhibition of L-type calcium channels.

With regard to anti-inflammatory activity, chamomile flower and aqueous myrrh extract (0.1–100 mg/ml) normalised the TNBS-induced overexpression of TNFα-mRNA as well as TNBS-induced loss of contractility and decrease in mucosa layer thickness concentration-dependently, whereas coffee charcoal (0.1-100 µg/ml) had no effect in the TNBS inflammation model. LPS-induced TNFα release from THP-1 cells was inhibited concentration-dependently by ethanolic myrrh extract (IC50 = 60.65 µg/ml), chamomile flower extract (IC50 = 439 µg/ml) and coffee charcoal extract (IC50 = 1886 µg/ml). Furthermore, chamomile flower (200 µg/ml) and coffee charcoal extract (500 µg/ml) markedly influenced the gene expression profile of LPS/IFNγ-stimulated human macrophages. Coffee charcoal inhibited the LPS/IFNγ-induced expression of genes associated with chemokine signalling.

Conclusion: The presented study demonstrates the pharmacological potential of the herbal ingredients of the fixed combination with respect to its spasmolytic and anti-inflammatory activities within a multi-target principle. Taken together, it could be demonstrated that the components are able to target gastrointestinal disorders by exerting antispasmodic and anti-inflammatory effects which reinforce the reported clinical effectiveness.

Disclosure of Interest: C. Vissiennon Financial support for research: Funding for experimental studies was provided by Repha GmbH Biologische Arzneimittel, K.-H. Goos Shareholder: Repha GmbH Biologische Arzneimittel, O. Goos Shareholder: Repha GmbH Biologische Arzneimittel, J. Arnhold Financial support for research: Funding for experimental studies was provided by Repha GmbH Biologische Arzneimittel, K. Nieber: None declared

P0443 FOUR YEARS FOLLOW UP OF GUT-DIRECTED GROUP HYPNOSIS IN PATIENTS WITH REFRACTORY IRRITABLE BOWEL SYNDROME – A LONG TERM SUCCESS

G. Moser¹, B. Weiskopf², S. Ortmayr¹, J. Peter¹

¹Internal Medicine III, ²Medical University of Vienna, Vienna, Austria

Contact E-mail Address: gabriele.moser@meduniwien.ac.at

Introduction: We previously showed that gut directed group-hypnosis (GHT) has a significant beneficial effect for patients with refractory irritable bowel syndrome (IBS).

Aims & Methods: Aim of this follow up (FU) study was to investigate long-term effects of GHT over four years. All 46 participants with GHT of our previous randomized controlled trial were invited to complete the IBS-impact scale (IBS-IS) for IBS related quality of life (higher values mean less complaints), the hospital anxiety and depression scale (HADS), visual analogue scales (VAS) for physical and psychological well-being as well as individual IBS symptoms.

Results: 30/46 patients (65%) completed all FU-questionnaires. After a mean duration of 4.13 years FU IBS-related quality of life and affective status showed a significant improvement compared to baseline (IBS-IS: 3.53 vs. 5.38 at FU, p<.001; HADS-depression: 6.28 vs. 4.14 at FU, p<.05; HADS-anxiety: 9.69 vs. 6.83 at FU, p<.001). Also VAS-scores for physical and psychological well-being, as well as individual symptoms revealed a significant improvement (p<.001, respectively p<.01). Gender, IBS-subtype and practising of hypnosis had no influence on this success of GHT.

Conclusion: The beneficial effects of GHT are long lasting over 4 years in patients with refractory IBS. Therefore GHT is a highly valuable therapy option and should be offered in tertiary centres.

Disclosure of Interest: None declared

P0444 A DOUBLE-BLIND RANDOMISED CONTROLLED TRIAL OF THE EFFECT OF DIETARY FERMENTABLE CARBOHYDRATES ON THE COLON USING MAGNETIC RESONANCE IMAGING: SUPPLEMENTARY OLIGOFRUCTOSE INCREASES COLONIC VOLUME BUT SO DOES THE LOW FODMAP DIET

G. Major¹, S. Krishnasamy², C. Mulvenna², S. Pritchard³, C. Hoad³, L. Marciani¹, M. Lomer⁴, P. Gowland³, R. Spiller¹, on behalf of the University of Nottingham GI MRI Research Group

¹NIHR Nottingham Digestive Diseases Biomedical Research Unit, ²Nottingham Digestive Diseases Centre, ³Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, ⁴Diabetes and Nutritional Sciences Division, King's College, London, United Kingdom

Contact E-mail Address: robin.spiller@nottingham.ac.uk

Introduction: Magnetic Resonance Imaging(MRI) can be used to assess gastrointestinal (GI) function non-invasively without the use of ionising radiation. An uncontrolled pilot study (UEGW2014) found that supplementing the diet of healthy volunteers for a week with oligofructose(OF) 5g bd increased fasting colonic volume by 18%. Adoption of a diet low in fermentable oligo-, di-, mono-saccharides and polyols (FODMAPs), such as OF, has been shown to reduce symptoms of irritable bowel syndrome.

Aims & Methods

Aim: to investigate the effect of altering the amount of fermentable carbohydrate in the diet on colonic physiology and fermentation. The hypotheses were 1) starting a low FODMAP diet would reduce colonic volume, 2) supplementing the diet with OF would abolish the effect.

Methods: A parallel group, double-blind, randomised controlled trial in adult volunteers without previous GI disorders. Subjects followed their usual diet for a week. At 0800 on day 7 they swallowed 5 MRI transit markers, were counselled on the low FODMAP diet by a registered dietitian and were given a standard food package (UK diet) for the rest of the day. At 0800 on day 8 they attended fasted for MRI scan and tests of breath hydrogen (H₂) and methane (CH₄). All subjects then followed the low FODMAP diet for a week, but were randomised to take Maltodextrin (MD) or OF 7g bd. On day 7 transit markers and testing were repeated with another standard food package (low FODMAP). Supplement was continued until the night before tests.

Primary endpoint: percentage change from baseline in colonic volume. Secondary endpoints: a measure of whole gut transit, the weighted average position score of the transit markers 24h after ingestion (WAPS24); breath H₂ and breath CH₄. Food diaries were kept for both weeks preceding MRI.

Results: Data presented as mean (95%CI). 37 subjects completed the study (19OF:18MD). One subject (MD) had corrupted images and was excluded from MRI analysis. Compliance with diet and supplements was good. Contrary to our hypothesis CV increased on MD from 650mL (558–742) to 740mL (616–865) or 15.5% (2.5–28.4, p < 0.05). The increase was greater in the OF group: from 693mL (620–765) to 803mL (732 —874) or 19.6% (6.5–32.7, p < 0.01) but the difference between groups was not significant. Breath H₂ response of the groups diverged (p < 0.01): on MD H₂ fell by 11ppm (3–18) but on OF H₂ rose by 16ppm (−2–35). WAPS24 and CH₄ did not change from baseline significantly in either group, with no difference between groups.

Conclusion: Fasting breath hydrogen fell on a low FODMAP diet and rose with OF use, confirming previous studies^1,2. Contrary to the study hypothesis colonic volume increased significantly on the low FODMAP diet, an effect that may be due to the presence of replacement substrate for colonic bacteria in substituted foods (e.g. tapioca or potato). Since the low FODMAP diet did not lead to a reduction in colonic distension other mechanisms for any clinical effect, such as changes in the microbiota, may need consideration.

Disclosure of Interest: None declared

P0445 A SINGLE-BLIND STUDY EVALUATING THE EFFECTS OF A GLUTEN-FREE DIET IN DIARRHOEA PREDOMINANT IRRITABLE BOWEL SYNDROME

I. Aziz¹, J. North¹, N. Trott¹, R. Briggs¹, D. S. Sanders¹

¹Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, United Kingdom

Contact E-mail Address: imran.aziz@sth.nhs.uk

Introduction: Gluten has been shown to alter bowel barrier function in patients with diarrhoea-predominant irritable bowel syndrome (D-IBS), particularly those who are HLA-DQ2 and/or DQ8 positive.

Aims & Methods: We aimed to assess the clinical response to a gluten-free diet (GFD) in D-IBS patients previously naïve to the effects of gluten and blinded to HLA-DQ status.

We enrolled 48 D-IBS patients (24 HLA-DQ negative and 24 HLA-DQ positive) to undertake a six-week GFD following dietetic input. Both patients and dietitian were blinded to HLA-DQ status. Validated questionnaires were self-completed at baseline and at week-6. The primary end-point was mean-change in IBS-severity scoring system (IBS-SSS), with a 50-point reduction conferring clinical benefit. Secondary end-points were change in hospital anxiety and depression score (HADS), fatigue impact score (FIS), and short-form 36 (SF-36).

Results: Data from 41 patients (74.4% women, mean-age 40.3yrs) was available for per-protocol-analysis. Of these, 21 were HLA-DQ negative and 20 HLA-DQ positive; baseline characteristics were similar other than worse pain-frequency (p=0.03), physical-fatigue (0.04), and vitality (0.05) in the HLA-DQ positive group. Overall, a GFD reduced IBS-SSS ≥50 points in 71% (n=29). In fact, the mean-total IBS-SSS decreased from 286 to 131 points (change -155, p < 0.001), which was seen similarly across both HLA-DQ groups. However, HLA-DQ negative subjects showed a greater reduction in abdominal distension in the first four weeks compared to HLA-DQ positive (P=0.04), although this was non-significant by week-6. There was a marked improvement in HADS, FIS, and SF-36 amongst both groups. However, HLA-DQ positive subjects showed a greater response to depression (p=0.02), fatigue (physical, p=0.04; cognitive, p=0.07) and vitality (p=0.05) compared to HLA-DQ negative subjects. On study completion, 90% (n=37) were discharged and 61% (n=25) continued with a GFD.

Conclusion: A GFD is a therapeutic option for the management of D-IBS. A clinical improvement was seen in 71% of patients undertaking a six-week GFD, with 61% opting to continue with a GFD for the foreseeable future. The pathophysiological mechanism may differ according to HLA-DQ status.

Disclosure of Interest: None declared

P0446 IS THE RESPONSE TO IBODUTANT MAINTAINED IN IBS-D FEMALE PATIENTS AFTER STOPPING TREATMENT? AN IRIS-2 EXPLORATORY ANALYSIS

J. Tack¹, S. Scartoni², G. Tonini², K. Ott³, I. Koch³, I. Otranto², F. Masciopinto², K. Schumacher³, M. Bertolotti², A. Capriati², C. A. Maggi²

¹Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium, ²Corporate Clinical Research, Menarini Ricerche Spa, Florence, Italy, ³Corporate Clinical Research, A. Menarini Research & Business Service GmbH, Berlin, Germany

Contact E-mail Address: jan.tack@med.kuleuven.be; kaischumacher@menarini-berlin.de;

Introduction: Ibodutant, is a potent antagonist of neurokinin-2 receptors currently in phase III clinical development for Irritable Bowel Syndrome with Diarrhea (IBS-D). A phase II study (IRIS 2) tested the efficacy of 8-week oral treatment with 3 doses of ibotudant (1 mg, 3 mg, 10 mg) in 559 IBS-D patients defined by Rome III criteria. The treatment period was followed by a 2-week treatment-free withdrawal period. Based on the response to the binary question on the combined satisfactory relief of IBS symptoms and abdominal pain/discomfort a statistically and clinically relevant efficacy was demonstrated in the female subgroup (n=333) at the 10 mg dose (p= 0.003 over placebo).

Aims & Methods: To evaluate the maintenance of treatment response in the female IBS-D population exposed to ibodutant after 2 weeks of treatment withdrawal versus placebo.

During the whole study, patients reported on a weekly basis their overall IBS symptom relief and abdominal pain/discomfort relief (binary yes/no question: “Did you have satisfactory relief of your overall IBS symptoms during the last week?” and “Did you have satisfactory relief of your abdominal pain or discomfort during the last week?”). The rate of responders (50% rule) developed during the 2-week withdrawal phase was compared versus the last two weeks of treatment to assess the maintenance of effect.

Results: The frequency of responders given at week 7 to 8 (last 2 weeks of treatment) and at the end of the withdrawal phase (week 9 to 10) is given below.

IBS-D Females (N=333) No of Responders (%)	Ibodutant 1 mgN=89	Ibodutant 3 mgN=87	Ibodutant 10 mgN=79	Placebo N=78
Week 7-8	58 (65.2%)	52 (59.8%)	58 (73.4%)	41 (52.6%)
Week 9-10	51 (57.3%)	51 (58.6%)	47 (59.5%)	36 (46.2%)
Change %	7 (7.9%)	1 (1.2%)	11 (13.5%)	5 (6.4%)

The number of responders declined at the end of the 2-week treatment-free withdrawal phase in all treatment groups, with the maximum decline at the efficacious dose of 10 mg once daily (13.5% less patient who maintained their response during the withdrawal phase was lowest in the placebo group (approximately 6.4%)).

Conclusion: When ibodutant treatment was withdrawn and patients continued to report their IBS-symptoms the responder rates declined notably in the 10 mg treatment group, thus confirming the role of ibodutant as maintanance treatment in IBS-D. The highest decline at the 10 mg dose showing efficacy versus placebo, while comparatively well maintained response rate in the other treatment arms, gives additional evidence of the true treatment effect of ibodutant at 10 mg dose.

Disclosure of Interest: J. Tack Consultancy: Menarini Ricerche Spa, S. Scartoni Financial support for research: Menarini Ricerche Spa, G. Tonini Financial support for research: Menarini Ricerche Spa, K. Ott Financial support for research: Menarini Ricerche Spa, I. Koch Financial support for research: Menarini Ricerche Spa, I. Otranto Financial support for research: Menarini Ricerche Spa, F. Masciopinto Financial support for research: Menarini Ricerche Spa, K. Schumacher: None declared, M. Bertolotti Financial support for research: Menarini Ricerche Spa, A. Capriati Financial support for research: Menarini Ricerche Spa, C. Maggi Financial support for research: Menarini Ricerche Spa

P0447 ONE-YEAR FOLLOW-UP OF NURSE–ADMINISTERED GUT-DIRECTED HYPNOTHERAPY FOR PATIENTS WITH IBS

J. Lövdahl¹, G. Ringström¹, H. Törnblom¹, M. Simren¹

¹Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden

Contact E-mail Address: jenny.lovdahl@vgregion.se

Introduction: Gut-directed hypnotherapy is an effective treatment for patients with irritable bowel syndrome (IBS), but it is costly, time consuming and availability is a problem. We have recently reported good short-term effectiveness of nurse-administered, gut-directed hypnotherapy in a tertiary care centre (Lövdahl et al Am J Clin Hypnosis 2015).

Aims & Methods: Our aim was to determine the long-term results of nurse-administered, gut-directed hypnotherapy and to identify factors predicting treatment outcome at one-year follow-up. We included 85 patients with IBS (mean age 40 (20-70 years; 60 women) with symptoms refractory to standard management. Participants received hypnotherapy administered by a nurse once/week for 12 consecutive weeks. Response to treatment was assessed with the IBS Severity Scoring System, IBS-SSS before, during (6 weeks) and immediately after the hypnotherapy treatment period (12 weeks), as well as during follow-up at week 26 (n=77) and one year (n=68). Patients also completed questionnaires at baseline, week 12, 26 and one year assessing the severity of extracolonic symptoms, anxiety and depression and GI-specific anxiety.

Results: At the end of the treatment period, i.e. at week 12, 50 patients (59%) were responders (IBS-SSS score reduction ≥50). At follow-up (week 26 and one year), 86 and 79%, respectively, of responders at week 12, were still responders; in total the responder rate at both week 26 and one year was 62%. Compared to baseline, at the one-year follow-up patients reported marked improvement of IBS symptoms (IBS-SSS: 335 (253,384) vs. 212 (147,287) (median, (IQR); p < 0.0001) as well as of extra-colonic symptoms (p < 0.0001), GI-specific anxiety (p < 0.0001), general anxiety (p < 0.0001) and depression (p < 0.001) Responder status already at week 6 could predict the responder status of the patients at week 26 (p < 0.0001) and at one year (p=0.003), but no baseline variables could predict the one-year outcome. Being a responder at the one-year follow-up based on IBS symptom improvement (IBS-SSS score reduction ≥50 vs baseline) was also associated with a greater improvement in depression (p=0.01), GI-specific anxiety (p < 0.0001) and extra-colonic symptoms (p=0.002).

Conclusion: Nurse-administered gut-directed hypnotherapy is an effective treatment option with good long-term results for patients with IBS symptoms refractory to other treatments. A rapid clinical response during hypnotherapy predicts good long-term results, and the IBS symptom improvement at one year is associated with improvement also in psychological and bodily symptoms.

Disclosure of Interest: J. Lövdahl: None declared, G. Ringström: None declared, H. Törnblom Lecture fee(s): Almirall, Consultancy: Almirall, M. Simren Financial support for research: Danone Research, Lecture fee(s): Almirall, Shire, Tillotts, Takeda, Consultancy: AstraZeneca, Almirall, Shire, Danone Research, Nestlé, Chr Hansen

P0448 LARGEST REPORTED PROSPECTIVE EVALUATION OF A LOW FODMAP DIET IN IBS PATIENTS IN A REGIONAL HOSPITAL

J. Arts¹², J. Tack¹, A. Holvoet², S. Decock², T. Lanssens², P. Van Hootegem²

¹UZ Gasthuisberg, Leuven, ²AZ Sint-Lucas, Brugge, Belgium

Contact E-mail Address: joris.arts@stlucas.be

Introduction: The irritable bowel syndrome (IBS) is a highly prevalent condition with unclear underlying pathophysiology and for which no standard effective therapy is established. A number of recent studies have shown that fermentable oligo-, di-, mono-saccharides and polyols (FODMAPS) alter intestinal physiology and can trigger gastrointestinal symptoms, while a low FODMAP diet improves symptoms in tertiary care IBS patients.

Aims & Methods: Our aim was to perform a prospective study to determine whether a low FODMAP diet improves symptoms in IBS patients in the setting of a regional hospital in Belgium.

Consecutive IBS patients, seen at the gastroenterology outpatient clinic, were instructed how to take a low FODMAP diet by an experienced dietician. All patients were asked to score their symptom severity before and 8 weeks after the implementation of a low FODMAP diet. The intensity of 5 symptoms (bloating, abdominal cramps, borborygmi, stool disturbances, fatigue) was evaluated using 0 to 100 mm visual analogue scales (VAS). The global effect of the low FODMAP diet was also evaluated by means of a VAS (0mm = no improvement to 100mm = complete symptom resolution). VAS are reported as mean+/-standard deviation. Responses were compared using the Wilcoxon signed rank test. Results were considered significant if p < 0.001 .

Results: Eighty-two patients with IBS according to Rome III criteria, 83% females, mean age 39 ± 12 years, were included in this prospective study. After 8 weeks of low FODMAP diet, we found a significant reduction of global symptom score (sum of all evaluated symptoms) (318 ± 61 vs. 131 ± 61; p < 0.001). An improvement of >50% of the global symptom score was observed in 65% of the patients. The low FODMAP diet also improved all cardinal IBS symptoms (abdominal pain, 63 ± 21 vs. 29 ± 20 mm; bloating 58 ± 20 vs. 30 ± 22mm; flatulence 69 ± 18 vs. 30 ± 20 mm and stool disturbances (64 ± 20 vs. 30 ± 20mm) (all p < 0.001). In addition, fatigue was significantly less with a low FODMAP diet (63 ± 20 vs. 41 ± 26mm, p < 0.001). The global efficacy rating was 65 ± 24mm on the VAS. Of the 82 patients, 21 had a result of >90mm, these patients can be considered as complete responders.

Conclusion: A diet low in FODMAPs effectively reduces IBS symptoms and fatigue in secondary care practice. Robust symptom improvement occurs with a strict low FODMAP diet. To our knowledge, this prospective study is the largest reported trial in a regional hospital and confirms the results obtained in tertiary care centers. The results support the use of dietary intervention in IBS in general clinical practice.

Disclosure of Interest: None declared

P0449 LOW FODMAP ADVICE FOR PATIENTS WITH IRRITABLE BOWEL SYNDROME: LONG-TERM OUTCOMES FOR SYMPTOMS AND DIETARY INTAKE

L. Martin¹, C. J. van Vuuren¹, L. Seamark², M. Williams², H. Staudacher¹, P. Irving¹³, K. Whelan¹, M. Lomer¹⁴

¹King's College London, Diabetes and Nutritional Sciences Division, London, ²Community Dietetics Service, Somerset Partnership NHS Foundation Trust, Somerset, ³Gastroenterology, ⁴Dietetics, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom

Contact E-mail Address: miranda.lomer@kcl.ac.uk

Introduction: Short chain fermentable carbohydrate (FODMAP) restriction reduces symptoms of irritable bowel syndrome (IBS) and is routinely used in clinical practice. Comprehensive FODMAP education incorporates a low FODMAP exclusion diet for 4-8 weeks followed by FODMAP reintroduction to test individual tolerance. Patients are empowered to self-manage their diet and symptoms, however whether this approach is effective in the long term is unknown. Previous research has indicated that after 4 weeks of FODMAP exclusion, calcium intakes are low.

Aims & Methods: This study aimed to assess the long-term effectiveness of the low FODMAP diet and the impact on dietary intake in patients with IBS.

Patients with IBS (n=375) from primary and secondary care were invited to take part in a prospective questionnaire study after completion of comprehensive FODMAP education from a dietitian as described above. Symptoms were assessed at baseline before FODMAP education, following FODMAP exclusion (4-8 weeks) and following FODMAP reintroduction (6-18 months) using the global symptom question “Do you currently have satisfactory relief of your gut symptoms?” and the Gastrointestinal Symptom Rating Scale. Dietary adherence to long-term FODMAP restriction was assessed using a Likert scale and dietary intake was measured using a validated FODMAP FFQ and compared to UK dietary reference values (DRVs). Statistical analyses used the chi-squared test.

Results: Questionnaires from 103 patients were received (age: mean ± sd; 48 ± 15 years, female: n=76). Following FODMAP exclusion, 63 (61%) patients reported satisfactory relief. Of these, 44/63 (70%) continued to report satisfactory relief following FODMAP reintroduction in the long term. Of those who had satisfactory relief on initial FODMAP exclusion, significantly more reported absent or mild abdominal pain (n=52 vs n=20; P < 0.001), bloating (n=46 vs n=19; P=0.009), flatulence (n=45 vs n=12; P < 0.001), borborygmi (n=49 vs n=21; P=0.007), urgency (n=48 vs n=17; P=0.001), sensation of incomplete evacuation (n=49 vs n=21; P=0.007) and lethargy (n=46 vs n=20; P=0.018) over the long term, than those who did not have satisfactory relief on initial FODMAP exclusion. In the long term, 78 patients continued to follow an adapted low FODMAP diet and their total mean ± sd FODMAP intake was 20.9g ± 15.1 compared to 29.4g ± 22.9 for 19 patients following a normal diet. The mean ± sd calcium and iron intakes for the whole group (n=103) were 1130mg ± 682 and 13.7mg ± 4.6 respectively. Of the 78 who continued to follow an adapted low FODMAP diet, 59 (76%) and 55 (71%) patients met the calcium and iron DRVs.

Conclusion: The majority of patients who achieve satisfactory relief of symptoms following FODMAP exclusion continue to have satisfactory relief in the long term indicating that FODMAP education is useful for long-term symptom control and self-management. The majority of patients continue to follow an adapted low FODMAP diet and approximately three-quarters meet their calcium and iron requirements in the long term.

Disclosure of Interest: L. Martin Financial support for research: Dr Schar provided funding to support this work, C. van Vuuren: None declared, L. Seamark: None declared, M. Williams: None declared, H. Staudacher: None declared, P. Irving: None declared, K. Whelan: None declared, M. Lomer: None declared

P0450 GUT-DIRECTED HYPNOTHERAPY IS NOT INFERIOR TO THE LOW-FODMAP DIET IN REDUCING SYMPTOMS ASSOCIATED WITH IRRITABLE BOWEL SYNDROME: A RANDOMISED CLINICAL STUDY

P. Gibson¹, S. Peters¹, C. Yao¹, S. Shepherd¹, H. Philpott¹, G. Yelland¹, J. Muir¹

¹Gastroenterology, Monash University, Melbourne, Australia

Contact E-mail Address: peter.gibson@monash.edu

Introduction: Obtaining high-quality evidence for efficacy of gut-directed hypnotherapy (GDH) in patients with irritable bowel syndrome (IBS) is constrained by the difficulty in designing a blinded placebo. An alternative is to compare GDH to a therapy with proven efficacy, such as the low FODMAP diet (LFD), which benefited 70% of such patients in a recent randomised, controlled trial¹

Aims & Methods: This study aims to determine if GDH is non-inferior in efficacy to the LFD and to assess whether they have additive effects. A randomised controlled trial was performed in IBS patients (Rome-III) comparing (a) LFD: education at the beginning of week 1, review at week 6; (b) GDH: six weekly one-hour hypnosis sessions for 6 weeks; (c) a combination of both. The primary endpoint was the change in overall gastrointestinal (GI) symptoms as evaluated using a 100 mm visual-analogue-scale from baseline to week 6. Secondary end-points were the change overall GI symptoms from baseline to 6-months post-treatment and the change in individual gastrointestinal symptoms (abdominal pain, bloating, wind, satisfaction with stool consistency and nausea), psychological indices including anxiety and depression as assessed by the Hospital Anxiety and Depression Scale (HADS) and IBS-related Quality Of Life (QOL) from baseline to week 6 and 6-months post treatment.

Results: Of 74 participants (mean age 40, SD 14 y; 14 male), 25 received GDH, 24 the LFD, and 25 combination therapy. The groups were well matched. Overall GI symptoms improved from baseline to week 6 by mean [95% CI] of 33 [25, 41], 30 [19, 42] and 36 [27, 45] mm, respectively (all p<.0001) with no differences across the groups (p=.67; one-way-between-groups ANOVA). Improvement (≥20 mm reduction) was achieved in 72% who received GDH, 71% LFD and 72% combined treatment. Overall symptoms remained improved from baseline to 6 months by 38 [27, 50], 30 [16, 43] and 27 [14, 40] mm (p<.0001). 74% receiving GDH, 82% LFD and 54% combined treatment maintained their response. Significant reductions in abdominal pain, bloating, wind and stool consistency, but not nausea were observed from baseline to week 6 and 6 months. No differences in improvement were observed for individual GI symptoms across treatment groups at either timepoint. Anxiety significantly reduced at week 6 and was maintained 6 months post-treatment in those who received GDH and LFD. Long-term improvement for depression was only observed following GDH. IBS-QOL significantly improved in all treatment groups from baseline to week 6 but was only maintained 6-months post-treatment for those who received the combined treatment. No difference in any psychological index was observed across treatment groups from baseline to week 6 or 6-months.

Conclusion: Efficacy of GDH is not inferior to that of LFD for relief of GI symptoms in IBS patients, but they do not show additive effects. Improvement in in psychological status was in general independent of the mode of treatment. GDH is an effective alternative to the LFD, but the lack of additive effect is unexplained.

Disclosure of Interest: P. Gibson Conflict with: Published book on diet in IBS, S. Peters: None declared, C. Yao: None declared, S. Shepherd Conflict with: Published books on diet in IBS and coeliac disease, H. Philpott: None declared, G. Yelland: None declared, J. Muir: None declared

P0451 GENDER RELATED DIFFERENTIAL EFFECT OF TACHYKININ NK2 RECEPTOR-MEDIATED VISCERAL HYPERALGESIA IN GUINEA PIG COLON

S. Meini¹, F. Bellucci¹, R. Bugianesi², A. Crea², V. D'Aranno², P. Santicioli¹, M. Tramontana¹, C. A. Maggi¹

¹Pharmacology, Menarini Ricerche, Florence, ²Pharmacokinetic, Menarini Ricerche, Pomezia, Italy

Contact E-mail Address: smeini@menarini-ricerche.it

Introduction: The tachykinin NK₂ receptor antagonist ibodutant is currently under clinical investigation for treating irritable bowel syndrome (IBS) with diarrhea, having shown a greater efficacy in female gender (Tack et al., 2013).

Aims & Methods: Aim of this study was to investigate the NK₂ receptor-related gender specificity in a model of colon visceral hyperalgesia. Colitis was induced by rectal instillation of TNBS (0.5 ml, 30 mg/ml in 30% ethanol) in female and male guinea pigs. Electromiographic visceromotor responses (VMR) to colorectal distension (CRD, 0.5-1-1.5-2 ml) was evaluated 3 days after. Ibodutant was evaluated at the doses of 0.33, 0.65, 1.9, and 6.5 mg/kg (s.c., 30 min before CRD) both in inflamed and control animals. The release of neurokinin A (NKA) following treatment (15 min superfusion) of KCl (80 mM) or capsaicin (10 µM) was measured by EIA in both mucosal and smooth muscle dissected distal colon tissues of control and inflamed animals. Pharmacokinetic parameters of ibodutant following a single s.c. administration (0.73 or 2.1 mg/kg .) were measured in the plasma (0-24h).

Results: Ibodutant did not affect VMR following CRD in control animals at any of the used doses. After TNBS-induced colitis ibodutant inhibited the increased visceral hypersensitivity (evident at the lower CRD volume) in female animals by 55 ± 15% at 0.33 mg/kg dose, and the inhibition was total at the higher doses. In male animals the ibodutant 0.65 mg/kg dose was uneffective, and the 1.9 mg/kg inhibited the VMR by 79 ± 9%. Ibodutant pharmacokinetic parameters did not differ between females and males at both tested doses (0.73 and 2.1 mg/kg). NKA was released following KCl and capsaicin treatment and it was generally greater in smooth muscle than in mucosal specimens. Differences dependent on the animal gender were evident in the release from distal colon and especially in the mucosal preparations: the NKA release induced by KCl in control males was 3.9-fold greater than in female preparations (P=0.0469).

Conclusion: Present results indicate that ibodutant is effective in preventing abdominal pain in a model of visceral hypersensitivity in guinea pigs with a greater efficacy in females. The differences observed in mucosal nerve activation may reflect its participation in colonic visceral hypersensitivity (Hoffman, 2012), and possibly gender related differences.

Disclosure of Interest: None declared

P0452 EFFECTIVENESS AND TOLERABILITY OF LINACLOTIDE IN THE TREATMENT OF IBS-C IN A REAL-WORLD SETTING: RESULTS FROM A GERMAN NON-INTERVENTIONAL STUDY

V. Andresen¹, S. Diemert², S. Miehlke³, E. Beck⁴, A. Prechtl², P. Layer¹

¹Israelitisches Krankenhaus, Hamburg, ²Almirall Hermal GmbH, Reinbek, ³Facharztzentrum Eppendorf, Hamburg, ⁴Anfomed GmbH, Moehrendorf, Germany

Contact E-mail Address: sebastian.diemert@almirall.com

Introduction: Recent studies suggest that symptom control of IBS-C is only rarely achieved with medications traditionally used for this disorder¹. Linaclotide is the first compound licensed by the EMA for the treatment of moderate to severe IBS-C. In two phase 3 clinical trials, linaclotide has been shown to significantly improve major symptoms of IBS-C including abdominal pain/discomfort, bloating and constipation². How clinical efficacy translates into effectiveness in a european real world setting, however, has not been investigated.

Aims & Methods: This study sought to elucidate the effectiveness and tolerability of linaclotide in the treatment of IBS-C in everyday clinical practice in Germany. The study was designed as a multicentre, non-interventional, prospective study, scheduled over 12 months. Patients included, were ≥18 years old and suffered from moderate to severe IBS-C. The decision for treatment with linaclotide was taken solely by the attending physician prior to study initiation. Data was recorded during regular patient visits (approx. 0, 4, 12, 24 weeks after start of treatment and in week 52 or at the end of treatment). Endpoints for measuring effectiveness include among others abdominal pain and bloating (11-NRS) and number of bowel movements. Tolerability was assessed recording the frequency and severity of adverse Events (AE) as well as the physician´s evaluation of tolerability.

Results: 79 centers participated in the study, 375 patients were enrolled. The average time of observation was 4.4 months (median 5 months). Abdominal pain [11-NRS] improved by more than 50% compared to baseline (4.9 points at baseline vs. 2.4 points at 12 months (LOCF); p< 0.0001). Intensity of bloating [11-NRS] improved to a similar degree (5.3 points at baseline vs. 2.7 points at 12 months (LOCF); p< 0.0001). Bowel movements increased from 2.7 per week at baseline to 4.4 at 12 months (LOCF), p< 0.0001. A subgroup analysis revealed, that patients who had failed to receive symptom relief when taking a traditional IBS-C medication prior to study initiation, showed a similarly pronounced treatment response to linaclotide as the overall study population. More than 90% of physicians assessed the tolerability at 6 months as either excellent or good. 50 adverse events (AE) occurred in 27 patients. Three AE in two patients were reported as serious (diarrhea and abdominal cramps). Upon cessation of treatment both patients recovered within one day.

Conclusion: Linaclotide proved to be safe and effective in reducing major symptoms of IBS-C in everyday clinical practice. Further, this study indicated, that patients with a history of failed treatment attempts for IBS-C, alike may benefit from Linaclotide. The improvement of IBS-C symptoms in response to linaclotide, as found in this study, was comparable to that seen in clinical trials.

Disclosure of Interest: V. Andresen Conflict with: speaker or scientific advice: Almirall, Astra-Zeneca, Boehringer-Ingelheim, Falk, Mundipharma, Shire, Yakult, S. Diemert Conflict with: employee of Almirall Hermal, S. Miehlke: None declared, E. Beck Consultancy: Almirall Hermal, A. Prechtl Conflict with: employee of Almirall Hermal, P. Layer Conflict with: speaker or scientific advice: Abbott, Almirall, Aptalis, Norgine, Shire

P0453 INCIDENCE OF COLON CANCER AFTER TREATMENT OF ACUTE COLONIC DIVERTICULITIS IN JAPAN

A. Mizuki¹, M. Tatemichi², A. Nakazawa³, N. Tsukada³, H. Nagata¹, T. Kanai⁴

¹Keiyu hospital, Yokohama, ²Tokai University School of Medicine, ³Saiseikai Central Hospital, Tokyo, ⁴School of Medicine, Keio University, Tokyo, Japan

Contact E-mail Address: amizuki@highway.ne.jp

Introduction: Although a few studies have reported the relation between colon cancer and acute colonic diverticulitis (ACD) in western countries, it had not yet been examined in Japan.

Aims & Methods: The purpose of this study was to determine the relationship between ACD and colon cancer in Japan. This study protocol was approved by the ethics committee at Tokyo Saiseikai Central Hospital (TSCH). Between January 1998 and January 2009, 420 ACD patients were diagnosed and treated in TSCH. ACD diagnosis was established by US and/or CT. Patients were treated conservatively and/or surgically. In tracking the patients, questionnaires were sent in order to obtain information on the development of colon cancer. The Cox proportional hazards model was performed to identify risk factors for colon cancer using information about family history of colon cancer, polyps, BMI (body mass index), physical exercise, dietary preferences (meat intake, fiber intake, etc.) smoking habits and alcohol consumption.

Results: One hundred and eleven patients answered the questionnaires, and their median (intraquarter range) follow-up periods were 9.3 (5.3) years. Nineteen patients had a history of recurrent ACD. The patient characteristics are summarized in Table 1. Three cases (2.7%) after treating ACD developed colon cancer. In this study, the incidence rate was calculated to be 276.3/year*million (mean age 55.5 years-old), while the recent incidence rate of colon cancer among 55 to 60-year-old Japanese is estimated to be 90.975/year*million. Case 1: a 68-year-old male without a history of ACD was diagnosed with colon cancer and surgically treated 5 months after being treated for ACD. The severity of ACD was moderate and had been treated conservatively. Case 2: a 60-year-old female without a history of ACD was diagnosed with colon cancer and surgically treated a month after being treated for ACD. The patient’s ACD was complicated by a small abscess and was treated conservatively. Colon cancer was not identified through a CT at admission, but was diagnosed by colonoscopy a month after ACD treatment. Case 3: a 68-year-old female with a history of ACD was diagnosed with colon cancer and surgically treated 43 months after being treated for ACD. She was also treated for colon polyps at the same time. The severity of ACD was moderate and treated conservatively.

Table1.

Patients Characteristics

	n=111
Presenting features
Mean (range) age (yr)	55.4 (18-91)
Gender (M/F)	72/39
Location of ACD (Rt/Lt)	75/36
Hx. of recurrent ACD	19
Complicated ACD	9
Treatment of ACD (conservative/surgery)	107/4
Family Hx. of colon cancer	9
Family Hx. of colon polyp	8
Occurrence of colon cancer	3
Occurrence of colon polyps	27

Conclusion: We found three cases of colon cancer post ACD. The incidence rate seems to be higher than that in the general population, but we are not able to conclude the relationship between ACD and colon cancer because of the small number of cases and the short duration of tracking time.

Disclosure of Interest: None declared

P0454 SYMPTOMATIC UNCOMPLICATED DIVERTICULAR DISEASE OF THE COLON DOES NOT SHOW ALTERATION OF FECAL MICROBIOTA

A. Tursi¹, W. Elisei², M. Picchio³, G. Giorgetti⁴, P. Mastromarino⁵, D. Capobianco⁵, M. Di Fonzo⁶, G. Brandimarte⁶

¹Gastroenterology Service, ASL BAT, Andria, ²Division of Gastroenterology, ASL Roma H, Albano Laziale (Roma, ³Division of Surgery, “P. colombo” Hospital, ASL Roma H, Velletri (Roma), ⁴Digestive Endoscopy and Nutrition Unit, “S. Eugenio” Hospital, ⁵Department of Public Health, Section of Microbiology, “Sapienza” University, ⁶Division of Internal Medicine and Gastroenterology, “Cristo Re” Hospital, Rome, Italy

Introduction: Data on fecal microbiota in symptomatic uncomplicated diverticular disease (SUDD) of the colon are lacking. We assessed therefore fecal microbiota in SUDD, comparing it with patients with asymptomatic diverticulosis and with healthy people.

Aims & Methods: Seventeen female patients with SUDD (median age 64.5 ± 4.7 yrs, range 56-68 yrs), 16 female patients with asymptomatic diverticulosis (median age 61.6 ± 4.0 yrs, range 52-70 yrs) and 19 healthy women (median age 59.0 ± 5.0 yrs, range 563-69 yrs) were analysed. Patients came from the same residence area.

Stool samples were collected at least 4 weeks after colonoscopy. Real-time PCR was used to quantify targeted microorganisms using the Applied Biosystems 7500 Real-Time PCR instrument. Bifidobacterium genus, Clostridium coccoides group, Bacteroides-Prevotella group, Escherichia subgroup, Lactobacillus genus and Akkermansia muciniphila were assessed for the qualitative analysis.

Results: There were no differences in the demographic characteristics among the three groups. The overall bacterial quantity did not differ among the three groups. Thus, a colonic bacterial overgrowth was absent in SUDD (p=0.449). The quantitative analysis of bacterial populations in feces assessed by real-time PCR showed no difference in the numbers of rRNA gene copies neither for the total bacteria nor for the different types analysed in the stool samples in the three study groups (Akkermansia: p=0.298; Bacterioides: p=0.354; Bifidobacterium: p=0.876; Clostridium: p=0.463; Escherichia: p=0.728; Lactobacillus: p=0.633).

Conclusion: SUDD does not show colonic bacterial overgrowth nor any significant qualitative alteration of the fecal microbiota. Further studies are requested to investigate whether bacterial imbalance involving other bacterial strains may be detected in those patients.

Disclosure of Interest: None declared

P0455 THE ROLE OF ENDOSCOPIC THERAPY IN THE MANAGEMENT OF ACUTE COLONIC DIVERTICULAR BLEEDING

C. A. Martins¹, S. Barbeiro¹, M. Canhoto¹, F. Silva¹, L. Eliseu¹, C. Gonçalves¹, I. Cotrim¹, H. Vasconcelos¹

¹Gastroenterology Department, Centro Hospitalar de Leiria, Leiria, Portugal

Contact E-mail Address: catarinaamartins@gmail.com

Introduction: Colonic diverticular bleeding (CDB) may require endoscopic therapy in the acute setting to stop the hemorrhage and avoid surgery. However identification of the bleeding diverticula with endoscopic hemostasis is not always feasible.

Aims & Methods: The aim is to evaluate the efficacy of endoscopic hemostasis in acute CDB in a period of 5 years. We performed a retrospective observational study of patients who underwent endoscopic therapy in CDB between January 2010 and December 2014.

Results: 156 admissions with CDB in this period were identified. In 15.4% of cases the bleeding diverticula was identified and endoscopic treatment was attempted in all of them. 79.1% were male patients with mean age 78.4 ± 7.3 years. Hemostatic modalities employed: combination of adrenaline injection plus hemoclips in 54.2%, hemoclips in 20.8%, adrenaline in 16.7% and argon plasma coagulation in 8.3%. The rate of rebleeding was in 12.5% within the first 72 hours. Endoscopic hemostasis was attempted again in all cases of bleeding recurrence and it was well succeeded in 66.7%. However, 33.3% (n = 1) needed urgent surgical treatment.

Conclusion: Endoscopic therapy in CDB is safe and has a high success rate. The choice of endoscopic technique did not appear to influence the success of therapy.

Disclosure of Interest: None declared

P0456 NATURAL HISTORY OF ACUTE COLONIC DIVERTICULAR BLEEDING

C. A. Martins¹, S. Barbeiro¹, F. Silva¹, M. Canhoto¹, B. Arroja¹, L. Eliseu¹, C. Gonçalves¹, I. Cotrim¹, H. Vasconcelos¹

¹Gastroenterology Department, Centro Hospitalar de Leiria, Leiria, Portugal

Contact E-mail Address: catarinaamartins@gmail.com

Introduction: Colonic diverticular bleeding (CDB) is a common cause of lower gastrointestinal bleeding. Treatment measures may include endoscopic, radiological and surgical options.

Aims & Methods: The aim is to characterize epidemiological, clinical and endoscopic features of patients with CDB in a period of 5 years. We performed a retrospective observational study of patients with CDB admitted in a Gastroenterology unit between January/2010-December/2014.

Results: We included 126 patients with a total of 156 admissions. 59.6% were men and the mean age was 78.7 years (range 51 – 96). The average length of stay in the gastroenterology unit was 5 days. 30.1% required blood transfusion with a mean of 2.7 units of packed red blood cell units per transfused patient. 33.4% were under anti-platelets or non-steroidal anti-inflammatory drugs (NSAIDs) and 12.1% under anticoagulant therapy. Bleeding location was identified in 15.4% patients and endoscopic treatment attempted in these cases. Rebleeding rate was 29.5% with only 32.7% of these rebleeding in the first 30 days. Mortality rate was 1.9%.

Conclusion: CDB is usually self-limited and tipically managed with conservative treatment. Rebleeding is frequent although global morbidity/mortality is low. Many patients with CDB are under anticoagulantor antiplatelet therapy.

Disclosure of Interest: None declared

P0457 MUCOSAL IMMUNE ACTIVATION AND NERVE FIBER SPROUTING IN PATIENTS WITH SYMPTOMATIC UNCOMPLICATED DIVERTICULAR DISEASE

C. Cremon¹, M. R. Barbaro¹, L. Bellacosa¹, M. Carapelle¹, G. Marasco¹, E. Scaioli¹, A. Colecchia¹, D. Festi¹, V. Stanghellini¹, G. Barbara¹

¹University of Bologna, Bologna, Italy

Contact E-mail Address: cesare.cremon@aosp.bo.it

Introduction: The pathogenesis of diverticular disease is still uncertain but it is thought to be multifactorial, involving environmental, colonic sensory-motor and structural factors. Symptomatic uncomplicated diverticular disease (SUDD) is a syndrome characterized by recurrent irritable bowel syndrome (IBS)-like symptoms attributed to diverticula in the absence of other macroscopically evident alterations. We hypothesized that colonic immune activation plays a role in symptom generation in patients with SUDD.

Aims & Methods: Thus, we characterized immune cells, nerve density and sprouting in patients with SUDD, diverticulosis and healthy controls (HC). For this, a total of 38 subjects were enrolled, of which 14 as HC, 16 with colonic diverticulosis, and 10 with SUDD. In patients with diverticula, mucosal biopsies were obtained close to diverticula and at least 20 cm from the last observed diverticula (normal mucosa). In HC, biopsies were performed at sigmoid and at descending colon. The expression of tryptase (mast cell marker), CD3 (T cell marker), CD68 (macrophage marker), neuronal specific enolase (NSE) [nerve marker], and growth-associated protein 43 (GAP-43) [neuronal outgrowth marker] was assessed by quantitative immunohistochemistry. IBS-like symptom severity and frequency were graded from 0 to 4, by means of validated symptomatic questionnaires.

Results: Mast cells were significantly increased in the peridiverticular mucosa of patients fulfilling the Roma III criteria for IBS, in comparison with HC (5.9 ± 0.7% vs 3.6 ± 0.5%; P < 0.05), but not in patients with SUDD as compared to diverticulosis or HC. No differences were detected in the T cell counts among the three groups. Macrophages were significantly increased in patients with SUDD and diverticulosis as compared to HC, both in the peridiverticular (5.8 ± 0.4%, 6.9 ± 0.6%, 4.9 ± 0.4%, respectively; P < 0.05) and in normal mucosa (7.1 ± 0.7%, 6.6 ± 0.4%, 4.0 ± 0.3%, respectively; P < 0.001). Similarly, the percentage of NSE+ fibers over lamina propria area was significantly enhanced in patients with SUDD and diverticulosis in comparison with HC (5.1 ± 0.7%, 5.5 ± 0.8%, 3.4 ± 0.4%, respectively; P < 0.05). Interestingly, GAP-43 immunoreactivity was significantly increased only in patients with SUDD as compared to HC (5 ± 0.6% vs 2.4 ± 0.7%, respectively; P < 0.05).

Conclusion: Mucosal immune activation, characterized mainly by macrophages, is a common characteristic of patients with diverticula regardless bowel symtpoms. Mast cells are increased only in patients with SUDD fulfilling Roma III criteria for IBS. Interestingly, nerve fiber sprouting is significantly increased only in patients with SUDD. Neuro-immune activation and sprouting may play a key role in symptom generation in patients with SUDD.

Disclosure of Interest: None declared

P0458 COLONIC DIVERTICULOSIS AND METABOLIC SYNDROME: A THREATENING ASSOCIATION?

C. Teixeira¹, D. Trabulo¹, S. Ribeiro¹, C. Martins¹, A. L. Alves¹, A. P. Oliveira¹, I. Cremers¹

¹Gastrenterology, Centro Hospitalar de Setubal, Setubal, Portugal

Contact E-mail Address: ac.corda.teixeira@gmail.com

Introduction: Colonic diverticulosis (CD) has been related with advanced age and lacking of diet fiber. Recently, several studies have shown that metabolic syndrome (MS) is also implicated in its etiopathogenesis.

Aims & Methods: This study aimed to assess the association between MS, obesity and CD. Prospective study within 1 year. Definition of MS according to NCEP-ATP III. Collection of demographic data, risk factors for MS and endoscopic findings of patients who underwent total colonoscopy in our department. Obesity was defined as BMI> 30 kg/m2. Informed consent was obtained. Local Ethic Committee and National Data Protection Committee approved the study. Statistical analysis was done with SPSS 21 and statistical significance was defined as p < 0.05.

Results: Two hundred and three patients, 95 males, mean age 65.5 years. CD was diagnosed in 30.5%. Right-sided diverticulosis was found in 3%, left-sided diverticulosis in 79% and pancolonic diverticulosis in 18%. Hypertension was present in 84%, dyslipidemia in 84%, diabetes mellitus (DM) in 47%, MS in 71.9%; 66.8% had increased waist circumference and 43% were obese. A significant association was found between CD and age (p=0), hypertension (P=0.02), dyslipidemia (p=0.046), increased waist circumference (p=0.033) and MS (p=0.003). There was no association with gender (p=0.76), obesity (p=0.47) or DM (p=0.836). There was no higher prevalence of adenoma or adenocarcinoma in patients with CD, in comparison with patients without CD.

Conclusion: In our series, MS was significantly associated with CD. The identification of risk groups is important since diverticulosis can have serious and potentially fatal complications. From our knowledge, this is the first European prospective study evaluating the association between MS and CD.

Disclosure of Interest: None declared

P0459 LOW PREVALENCE OF COLONIC DIVERTICULOSIS IN INFLAMMATORY BOWEL DISEASE PATIENTS

K. Takemoto¹, D. Kawai¹, S. Okanoue¹, E. Yasutomi¹, R. Takenaka¹, H. Tsugeno¹, S. Fujiki¹

¹Digestive Endoscopy, Tsuyama Chuo Hospital, Tsuyama, Japan

Contact E-mail Address: takemoto902@yahoo.co.jp

Introduction: Acquired colonic diverticulum is very common in developed countries and its prevalence increase with age. Colonic diverticulosis is associated with high intracolonic pressure and a weakened bowel wall. Chronic colitis is characterized by liquid stools with low intracolonic pressure and thickened bowel wall. And recently, several studies repoted mesalazine seems to be effective in preventing recurrence of acute uncomplicated diverticulitis.

Aims & Methods: The aim of this study was to assess the prevalence of colonic diverticulosis in inflammatory bowel disease patients, and to assess the prevalence of colonic diverticulosis in mesalazine-based treatment inflammatory bowel disease patients. We investigated that colonoscopy results (colonic diverticulosis) of patients with ulcerative colitis (UC) and Crohn's disease (CD) older than 30 years were retrospectively evaluated and compared with those of patients who underwent screening colonoscopy (control group) from April 2008 to April 2015 in our institution. And the prevalence of colonic diverticulosis was detected in the mesalazine-based treatment UC patients and CD patients compared with no mesalazine-based treatment UC and CD patients.

Results: UC patients were composed of 72 men and 68 women, with a mean age 51.3 years. CD patients were 30 men and 16 women, with a mean age 47.8 years. And control group were composed of 72 men and 68 women, with a mean age 52.3 years. The prevalence of colonic diverticulosis in UC patients was 20/140 (14%) and in CD patients was 3/46 (6%). And the prevalence of colonic diverticulosis in control group was 56/140 (40%). A significantly lower rate of colonic diverticulosis was detected in the UC patients and CD patients compared with the control group (p <0.001). But, no significant difference in the prevalence of colonic diverticulosis was detected between the UC patients and the CD patients (p <0.14). Next, the prevalence of colonic diverticulosis in mesalazine-based treatments UC patients was 14/120 (12%), no mesalazine-based treatments UC patients was 6/20 (30%). Mesalazine-based treatment UC patients was significantly lower percent of colonic diverticulosis was detected compared with no mesalazine-based treatments UC patients (p =0.01). But, the prevalence of colonic diverticulosis in mesalazine-based treatment CD patients was 2/38 (5%), no mesalazine-based treatment CD patients was 1/8 (13%). No significant difference in the prevalence of colonic diverticulosis was detected between the mesalazine-based and no-mesalazine treatment CD patients (p =0.49).

Conclusion: Inflammatory bowel disease (UC and CD) patients were lower prevalence of colonic diverticulosis. And in UC patients, we suggested that mesalazine can prevent occurrence of colonic diverticulosis.

Disclosure of Interest: None declared

P0460 DIFFERENT ABNORMALITIES IN LONGITUDINAL AND CIRCULAR MUSCULAR FUNCTION IN HUMAN COLONIC DIVERTICULAR DISEASE

L. Pallotta¹, A. Scirocco¹, A. Ignazzi², M. Maselli², A. Cicenia¹, M. Carabotti¹, G. De Toma¹, G. Tellan¹, F. Pezzolla², E. Corazziari¹, C. Severi¹

¹Sapienza University, Rome, ²Scientific Institute of Gastroenterology ‘‘S. de Bellis’’, Castellana Grotte (BA), Italy

Contact E-mail Address: luc.pallotta@gmail.com

Introduction: The pathogenesis of diverticular disease (DD) is multifactorial. Although several aetiological cofactors have been implicated in its pathogenesis, a relevant role seems to be played by an abnormal neuromuscular function. Derangement of enteric innervation has been described consisting in a decrease in cholinergic nerves and nitric oxide content, reduced density of interstitial cells of Cajal and enteric glial cells. Extensive structural changes in the muscle layer have also been reported with thickening, increased collagen and elastin deposition. However data on muscle function are scarce.

Aims & Methods: The aim of this study was to investigate the morpho-functional and molecular alterations inherent to the sigmoid colonic muscle of patients affected by DD. Longitudinal and circular smooth muscle cells (SMC) and strips were isolated separately from surgical colon specimen of 9 patients (58 affected by sigmoid DD and 9 patients (61 surgery for colon cancer. Contractile effects for muscarinic agonist acetylcholine (Ach 1μM) for cells and Carbachol (0.01-1000 µM) for strips, were tested. Relaxant effects were tested in response to vasoactive intestinal peptide (VIP 1μM). qPCR analysis was performed for transcription of muscarinic M3, VIP (VPAC1/VPAC2), Natriuretic Peptide Clearance (NPR-C) receptors and endothelial nitric oxide synthase (eNOS). qPCR data were normalized to β-actin mRNA. Data are expressed as mean ± SE, p < 0.05 considered significant.

Results: In DD, an impairment in cholinergic-induced contraction was observed on longitudinal smooth muscle. A significant decrease contractile response was observed both on muscle cells (9.8%±1.4 vs 16.8%±1.8) and strips (830 ± 54 vs 1644 ± 173 mN/cm²) and resulted associated to a significant decrease of transcripts for M3 receptors compared to control (6.8 ± 0.18 vs 7.98 ± 0.45). No alterations between normal and DD circular SMC were instead observed in contractile responses and cholinergic receptors expression. Relaxation in turn was impaired in circular, but not in longitudinal muscle. DD circular SMC presented a significant decrease in VIP-induced relaxation (33.3%±8.3) in respect to control (93.2%±1.4) that was associated to a significant decrease of transcripts for: VPAC1 (8.7 ± 4.4 vs 15.6 ± 0.1), VPAC2 (9.0 ± 0.4 vs 13.2 ± 1.0), NPRC (9.5 ± 0.03 vs 15.2 ± 0.3) and eNOS (10.3 ± 0.9 vs 14.7 ± 0.2).

Conclusion: Different molecular alterations occur in sigmoid longitudinal and circular muscle in DD that impair SMC response to enteric neurotransmitters. These myogenic alterations likely contribute to neuromuscular disorders in DD.

Disclosure of Interest: None declared

P0461 EVALUATION OF THE EFFECTS OF MESALAMINE AND PROBIOTICS ON FAECAL CALPROTECTIN LEVELS IN PATIENTS WITH SYMPTOMATIC UNCOMPLICATED DIVERTICULAR DISEASE

M. Bafutto¹, M. B. G. Costa², A. A. F. Bafutto², E. H. F. Bafutto², E. C. D. Oliveira³, J. Rezende Filho⁴

¹Departamento de Gastroenterologia da Universidade Federal de Goiás, Brasil, ²Instituto Goiano de Gastroenterologia, ³Departamento de Cirurgia da Universidade Federal de Goiás, Faculdade de Medicina Universidade Federal de Goiás, Brasil, ⁴Departamento de Gastroenterologia da Universidade Federal de Goiás, Faculdade de Medicina Universidade Federal de Goiás Brasil, Goiânia, Brazil

Contact E-mail Address: maurobafutto@uahoo.com.br

Introduction: Recent observations suggest that symptomatic uncomplicated diverticular disease (SUDD) is related to change in the colonic microflora and to low-grade inflammation. Faecal calprotectin (FC) levels are related to intestinal inflammation. Mesalamine can improve symptoms and reduce FC levels to a normal range in many patients, but in some FC may persist elevated. The management of these patients is presently unknown.

Aims & Methods: Evaluate the effects of the combined use of mesalazine and probiotis or the increase of mesalamine dose in SUDD patients with persistent elevated FC after mesalamine treatment. One hundred and ten patients (18 y or more) were selected after a clinical interview, colonoscopy, abdominal CT and FC test > 150 microgr/gr. Patients with intestinal neoplasia, previous intestinal surgery, use of antinflammatory drugs and concomitant disease with intestinal inflammation were excluded. The patients were medicated with mesalamine 800 mg b.i.d. for 60 days, and another FC test was done. Patients that presented FC > 150 microgr/gr (32, 2 pts excluded) were divided in two groups – 1) Mp Group – 15 patients that used mesalamine 800mg b.i.d. and a mix of probiotics (L. acidophilus, L.casei, L. lactis, B. lactis, B. bifidum) b.i.d. for 8 days; 2) M3 Group – 15 patients that used mesalamine 800 mg t.i.d for 8 days, and another FC test was done. Paired t test was used for statistical analysis.

Results: After 60 days of treatment with mesalazine 800 mg b.i.d, 78/110 (71%) patients presented FC <150 microgr/gr and 32/110 (29%) FC >150 microgr/gr. There was a statistically significant decrease (51.8%) in FC levels after combined treatment (Mp Group) (309.70 ± 121.80 x150.80 ± 104.23, p < 0.002). There was also a statistically significant decrease in FC levels (42.2%) after treatment with higher dose of mesalazine (M3 Group) (455.40 ± 264.17 x 261.50 ± 209.16; p < 0.01). FC levels reduced more (51.8%) in Mp than in M3 group (42.2%), but no statistically significant differences in post treatment FC levels were seen when Mp and M3 groups were compared.

Conclusion: FC decrease to normal range in most SUDD patients after treatment with mesalamine 1.6g. The combined use of mesalamine and probiotics or increasing the dose of mesalamine to 2.4 g may decrease FC in SUDD patients that persisted with FC elevated.

Disclosure of Interest: None declared

MONDAY, OCTOBER 26, 2015   09:00-17:00

OESOPHAGEAL, GASTRIC AND DUODENAL DISORDERS I – HALL 7__________

P0462 PROTEASE-ACTIVATED RECEPTOR-1 SIGNALING DEEPLY PARTICIPATES IN THE ABILITY OF TUMORIGENESIS BY CONTROLLING HIPPO-YAP PATHWAY

D. Fujimoto¹, Y. Hirono¹, T. Goi¹, A. Yamaguchi¹

¹First Department of Surgery, University of Fukui, Fukui, Japan

Contact E-mail Address: fujimoto@u-fukui.ac.jp

Introduction: Control of cell number is important in animal development and tissue homeostasis, and its dysregulation may result in tumor formation or organ degeneration. The Hippo pathway plays crucial roles in organ size control and tumorigenesis. The activity of YAP/TAZ, a transducer of the Hippo pathway, is required to sustain self-renewal and tumor-initiation capacities in cancer stem-like cells (CSCs). But, upstream signals that control the mammalian Hippo pathway have not been well understand. Here, we reveal that the connection between Protease-activated receptor 1 (PAR1) signaling pathway and the Hippo-YAP pathway in gastric cancer.

Aims & Methods: MKN45 cells stably expressing PAR1 (MKN45/PAR1) were established in our laboratory(1). siRNA against PAR1 was synthesized. We studied the change in fraction of side population cell, compared the tumorgenesis in nude mice, and increased dephosphorylated YAP protein levels in nucleus, when PAR1-expressing cell line (MKN45/PAR1 and MKN74), PAR1-null expressing cell line MKN45 (control cell) and inhibited PAR1-expressing cell line MKN74 by PAR1 siRNA were treated with PAR1 agonist TFLLR-NH₂ or PAR1 agonist plus PAR1 selective antagonist SCH79797.

Results: The activity of PAR1 induces increase of the fraction of Side population cells which is enriched with CSCs. But the fraction of side population cells were not increased, when inhibited PAR1 activity. The statistical analysis of the ratios of tumor weight over total situs weight proved that PAR1 activated gastric cancer cell by TFLLR-NH₂ resulted in a significant increase of tumor burden (MKN45/PAR1 and MKN74 cells treated by TFLLR-NH₂ versus control, P<0.05). The peritoneal dissemination tumor weight of MKN45/PAR1 and MKN74 cells treated by TFLLR-NH₂ plus SCH79797 were small as compared to MKN45/PAR1 and MKN74 treated by TFLLR-NH₂ alone. A TFLLR-NH₂ inhibits the Hippo-YAP pathway kinase Lats via Rho GTPase, thereby activates YAP by decreasing phosphorylation and makes YAP increased in nucleus localization.

Conclusion: Our research identifies that PAR1 signaling deeply participates in the ability of tumorigenesis by controlling Hippo-YAP pathway signaling in gastric cancer stem cell. We presume that inhibited YAP will be a new target to treat human gastric cancer invasion and metastasis by dysregulated PAR1 or its agonists.

Disclosure of Interest: None declared

P0463 INCREASED EXPRESSION OF STEMNESS GENES IN HUMAN ADIPOSE TISSUE-DERIVED STEM CELLS (ADSCS) TREATED WITH PERITUMORAL ADIPOSE TISSUE CONDITIONED MEDIUM

E. Trevellin¹, A. Carraro², M. Scarpa³, A. Kotsafti³, A. Porzionato⁴, M. Cagol³, R. Alfieri³, U. Tedeschi², C. Castoro³, R. Vettor⁵

¹Medicine, University of Padova (Italy), Padova, ²General Surgery and Odontoiatrics, University Hospital of Verona, Verona, ³Oncological Surgery Unit, Veneto Oncological Institute (IOV-IRCCS), ⁴ Molecular Medicine, ⁵Medicine, University of Padova, Padova, Italy

Contact E-mail Address: elisabetta.trevellin@unipd.it

Introduction: Obesity is associated with an increased risk of cancer and it has been hypothesized that the action of adipokines may influence tumor microenvironment in esophageal adenocarcinoma (EAC) [1]. Moreover, the adipose tissue stromal vascular fraction is a reservoir of adipose tissue-derived stem cells (ADSCs): a mesenchimal multipotent cell population able to express genes considered as “stemness” markers.

Aims & Methods: Our aim is to investigate if peritumoral adipose tissue may play a direct role by altering the expression of stemness genes in human adipose derived stem cells (ADSCs).

Human ADSCs were isolated from obese patients undergoing bariatric surgery and were cultured with conditioned medium (CM) derived from adipose tissue fragments of peritumoral and distal depots of 15 patients with EAC, undergoing surgical resection. After 48h we measured mRNA levels of CD34, CD90, OCT-4 and nucelostemin (NSTM) in ADSCs using Real Time quantitative PCR.

Results: Gene expression CD34, CD90, OCT-4 and NSTM was significantly increased in ADSCs cultured with CM, compared to control untreated cells. In particular, expression of CD34, OCT-4 and NSTM was significantly higher in ADSCs cells cultured with CM of peritumoral depot, in comparison with ADSCs cultured with CM of distal depot. Moreover, the mRNA expression of CD34, OCT-4 and NSTM was increased in cells cultured with CM of peritumoral depot derived from patients with lymph node involvement (N+), compared to peritumoral CM of patients without lymph node involvement (N-).

Conclusion: Our results suggest that peritumoral adipose tissue may directly influence ADSCs through the action of secreted factors. In particular, the mRNA expression of CD34, OCT-4 and NSTM is up-regulated in ADSCs cultured with CM of peritumoral depot derived from patients with lymph node involvement. These observations lead us to hypothesize that adipose tissue may influence stemness of peritumoral adipocytes by a local paracrine signaling, thus creating a more permissive microenvironment for tumor invasiveness.

Disclosure of Interest: None declared

P0464 ALTERED APOB48 EXPRESSION CAN BE A MARKER OF SEVERE PANENTERIC DYSMOTILITY

F. Bianco¹², E. Bonora², I. Ceccherini³, M. Mosconi³, A. Gori², U. Volta², G. Caio², V. Stanghellini², G. Barbara², P. Clavenzani¹, M. Seri², R. De Giorgio²

¹DIMEVET, University of Bologna, Ozzano Dell' Emilia, ²DIMEC, University of Bologna, Bologna, ³U.O.C. Genetica Medica, Istituto Giannina Gaslini, Genova, Italy

Contact E-mail Address: franc.bianco19@gmail.com

Introduction: Severe panenteric dysmotility, mainly in the clinical phenotype of chronic intestinal pseudo-obstruction (CIPO), is a severe gut dysmotility characterized by recurrent sub-occlusion episodes with no evidence of any mechanical obstruction. CIPO is a heterogeneous term as it can be applied to a variety of patients for whom a diagnostic biomarker is still unavailable. The diagnosis of CIPO would certainly benefit from the identification of a biomarker. We recently showed an altered expression of APOB in familial CIPO patients carrying a novel RAD21 mutation and in a few sporadic CIPO patients. The aim of this study was to identify whether an altered APOB expression can be a possible biomarker for familial and / or sporadic CIPO by comparing CIPO patients to those with other conditions, e.g. Hirschsprung disease (HSCR, characterized by enteric neuron aganglionosis), irritable bowel syndrome (IBS) and motility unrelated disorders (i.e. celiac disease and non-celiac gluten sensitivity).

Aims & Methods: Sera and ileal biopsies of CIPO patients (n= 28; 18 F, age range: 17 - 67 years) and healthy controls (n= 10; 5 F, age range: 25-38) were used for western blot and quantitative immunohistochemistry. Sera from patients with HSCR, IBS and motility unrelated disorders (celiac disease and non-celiac gluten sensitivity, NCGS) (n= 40 each group) served as disease controls.

Results: Sera from idiopathic CIPO patients showed an elevated expression of APOB48, compared to healthy controls and to sera from patients with HSCR, IBS, celiac disease as well as NCGS. Consistently, the APOB48 signal was markedly increased at tissue level in ileum biopsies of CIPO cases compared to healthy controls and IBS (32.9 ± 9.2% vs 7.2 ± 2.5% cases vs controls; p= 0.0012, Student’ t test; 32.9 ± 9.2% vs 5.6 ± 1.5% CIPO cases vs IBS; p= 0.0008). Quantitative analysis performed in gut biopsies revealed also a significant reduction in the number of neuron specific enolase (NSE)- labeled myenteric ganglion cell bodies / ganglion in CIPO compared to control specimens (p= 0.0039).

Conclusion: APOB48 expression at serum and tissue level was homogeneously increased in sporadic CIPO highlighting a potential convergent mechanism on a gut-specific APOB isoform. The increased APOB48 can be exploited as possible biomarker to better differentiate CIPO from other diseases.

Disclosure of Interest: None declared

P0465 DIGITAL MICROSCOPY IS A VALID ALTERNATIVE TO CONVENTIONAL MICROSCOPY FOR DIAGNOSING BARRETT’S ESOPHAGUS

M. J. Van Der Wel¹², L. C. Duits¹, C. K. A. Seldenrijk³, G. J. Offerhaus⁴, M. Visser⁵, F. J. ten Kate⁴, J. G. Tijssen⁶, J. J. Bergman¹, S. L. Meijer²

¹Gastroenterology, ²Pathology, Academic Medical Center Amsterdam, Amsterdam, ³Pathology, St. Antoniusziekenhuis, Nieuwegein, ⁴Pathology, University Medical Center, Utrecht, ⁵Pathology, Zaans Medisch Centrum, Zaandam, ⁶Cardiology, Academic Medical Center Amsterdam, Amsterdam, Netherlands

Contact E-mail Address: m.j.vanderwel@amc.uva.nl

Introduction: Management of Barrett esophagus (BE) relies heavily on the histopathological assessment of biopsies. This assessment is subjective and associated with significant intra- and inter-observer variation. Most guidelines recommend review of biopsies by expert pathologists in case of low-grade or high-grade dysplasia (LGD/HGD). Conventional review of microscopy slides, however, is impractical and does not allow intercollegiate conferences or annotations of relevant findings in images for feedback. A digital revision platform would overcome these practical limitations.

Aims & Methods: In preparation of a national BE digital revision platform we compared the diagnostic accuracy of conventional and digital microscopy for diagnosing BE+/-dysplasia by a panel of expert pathologists. Sixty BE biopsy slides (NDBE; n=25, LGD; n=20; HGD; n=15) were scanned at x20 magnification. Five expert BE pathologists independently assessed all slides four times in 2 alternating rounds of digital and conventional microscopy. Assessments were supervised by a research fellow and the order of rounds as well as the order of the slides was randomized. Pathologists were blinded for the original diagnosis and identifying slide features. Intra-observer and pairwise inter-observer agreement were calculated using custom weighted Cohen’s kappa in four categories (NDBE; IND; LGD; HGD). Kappa scores were expressed as fraction of maximum possible kappa score for each cross table.

Results: The mean intra-observer agreement was 0.63 for the 2 rounds of digital assessment and 0.74 for the two rounds of conventional assessment. Mean pairwise inter-observer agreement was 0.61 and 0.64 for first and second round of digital microscopy, respectively. For the two rounds of conventional microscopy, mean pairwise inter-observer agreement was 0.62 and 0.66 respectively. In 48/60 (80%) of digital and in 50/60 (83%) of conventional microscopy reviews a majority diagnosis was reached after the first reading.

Conclusion: Diagnostic agreement of digital microscopy is comparable to conventional microscopy in the setting of an expert pathology platform for BE histology. This study validates the use of digital histopathological assessment of BE biopsies and will be used as the underlying infrastructure for a nationwide, web-based BE revision platform in the near future. This will overcome many logistical and practical issues concerned with conventional histologic review by multiple pathologists.

Disclosure of Interest: None declared

P0466 INHIBITION OF BMP2 AND BMP4 BY A NOVEL LLAMA-DERIVED NANOBODY SUSTAINS INTESTINAL STEM CELLS IN ORGANOID CULTURES

S. Calpe¹, A. Correia¹, C. Zimberlin², J. P. Medema³, K. K. Krishnadath¹

¹MDL, ²LEXOR, ³Academic Medical Center, Amsterdam, Netherlands

Contact E-mail Address: s.calpe@amc.nl

Introduction: “Intestinal organoids” are structures that mirror the intestinal crypt-villus units. They recapitulate the complete intestinal stem cell differentiation hierarchy and therefore are powerful therapeutic tools in which to study human disease models.

Inhibition of BMP activity is one of the requirements to maintain intestinal stem cells in these ex vivo cultures, and is usually provided by the addition of the natural BMP-inhibitor Noggin to the media. Noggin inhibits several BMPs, including BMP2,4 and 7. It is therefore not clear which BMPs are expressed by the intestinal organoid cultures and which need to be inhibited to sustain the stem cell culture.

Aims & Methods: Since BMPs have diverse and opposing roles understanding their specific function in the intestine is of great importance. Here, we set out to investigate which BMPs are required to maintain and culture organoids.

Results: We first tested which of our newly generated and highly specific aBMP nanobodies (VHHs) were able to maintain ex vivo stem cell organoid cultures. The three unique llama-derived VHHs with different specificities to BMPs: anti-BMP4 (C4); anti-BMP2,4 (C8); and anti-BMP2,4,5,6 (E7), were used. Addition of these VHHs to the organoid cultures resulted in a decrease in the total BMP activity. Whereas specific BMP4 inhibition (by C4) resulted in a partial decrease in the BMP activity, concomitant inhibition of BMP2 and BMP4 (by C8) was sufficient to result in an almost complete blockage of BMP signaling, to the same level as Noggin and E7. This indicated that the intestinal organoids mainly secrete BMP2 and BMP4. Consequently, inhibition of BMP2 and BMP4, but not BMP4 alone, was enough to sustain self-renewal of crypts as organoids cultured with C8 presented the same morphological characteristics as the ones cultured with Noggin, manifested by the presence of several crypt-like budding structures. Inhibition of BMP2,4,5,6 by E7 did not provide superior growth advantage to the cultures when compared to C8, suggesting that BMP5 and BMP6 are redundant in these cultures.

Conclusion: These results have important implications. First, inhibition of both endogenous BMP2 and BMP4 is enough to sustain self-renewal of small intestine stem cells in vitro and this can effectively and selectively be provided by C8, our BMP2,4-specific VHH. Since recombinant Noggin is expensive, C8 offers an easy accessible and cheaper alternative for these cultures. Second, specific inhibition of BMP4 alone does not affect stem cell proliferation. Therefore, C4 antibodies display important potential for therapeutic use in BMP4-mediated diseases, such as gastric cancer; as they would avoid the deleterious side effects of unchecked cancer stem cell proliferation observed by Noggin and other unselective inhibitors. Since inhibition of BMP5,6 is not required for intestinal stem cell cultures, future in vivo application of C8, would prevent detrimental effects of Noggin on for instance bone structures.

Disclosure of Interest: None declared

P0467 THROMBIN INDUCES HUMAN GASTRIC CANCER CELL TO EPITHELIAL-MESENCHYMAL TRANSITION THROUGH PAR1 ACTIVATION

T. Otsuki¹, D. Fujimoto¹, M. Morikawa¹, K. Koneri¹, M. Murakami¹, Y. Hirono¹, T. Goi¹, A. Yamaguchi¹

¹First Department of Surgery, Faculty of Medicine, University of Fukui, Eiheijicho,Yoshidagun, Japan

Contact E-mail Address: otsuki666@gmail.com

Introduction: Human α-thrombin, as a serine protease, catalyzes much coagulation-related reactions, and also promotes the activation of protease-activated receptors (PARs), a kind of G protein-coupled receptor, on the cell. We reported by using an immunohistochemical approach that PAR1 is expressing in the gastric cancer tissues, related poorer prognosis of patients, and its activation induces gastric cancer cells proliferation and invasion in vivo. Epithelial-mesenchymal transition (EMT) is defined as the process in which epithelial cells lose their cell-cell adhesion, and gain migratory and invasive properties to become mesenchymal stem cells, and plays a momentus role in cancer metastasis. These above facts underline the relevance of EMT and PAR1 acytivity to gastric cancer, but there are few reports on the role of PAR1 in EMT. This study investigates the role of PAR1 activity in EMT.

Aims & Methods: we investigated the expression levels of epithelial markers (Ecadherin and βcatenins) and mesenchymal markers (vimentin and fibronectin) by western blotting in the gastric cancer cells; pcDNA3.1 transfected MKN45 (MKN45/Mock), pcDNA3.1-PAR1 transfected MKN45 (MKN45/PAR1), and MKN74, stimulated by α-thrombin or α-thrombin with SCH79797, specific antagonist for PAR1. We observed that α-thrombin induced morphological changes, and immunofluorescence of E-cadherin and fibronectin expression in MKN45/PAR1 and MKN74 cells. We extracted these cells nuclear proteins and examined the binding of E-cadherin transcriptional factors to E-boxes (E1, E2 and E3) by means of EMSA and western blotting.

Results: Western blotting showed, epithelial and mesenchymal markers expression remains the same in MKN45/mock cells treated with α-thrombin for 24 h. But we observed the decreasing of epithelial markers expression and gain of mesenchymal markers expression in MKN45/PAR1 and MKN74 cells treated with α-thrombin. Furthermore, in MKN45/PAR1 and MKN74 cells, treated with α-thrombin and SCH79797, the decreasing of epithelial markers expression and gain of mesenchymal markers expression were suppressed. The morphological changes were observed from round- or epithelial-like to a spindle-like shape phenotype, and immunofluorescence showed the reduction of expression in E-cadherin and the gain of expression in fibronectin. EMSA showed the higher levels of Ebox13 protein complex bands in the MKN45/PAR1 and MKN74 cells treated a-thrombin, and in these cells treated with α-thrombin and SCH79797 showed suppressed levels of E-box complexes bands. We observed significant increase in nuclear levels of the Snail, one of the transcriptional factors of E-cadherin, by western blotting.

Conclusion: We found that α-thrombin induces PAR1 activation and undergo specifically EMT in gastric cancer cell lines. Inhibition of PAR1 signaling pathway may be a new strategy to prevent tumor invasion and metastasis.

Disclosure of Interest: None declared

P0468 EFFECTS OF PGP AND N-ACETYL-PGP AND CYTOKINE PRODUCTION IN SERUM ON THE DEVELOPMENT AND HEALING OF ACETATE ULCERS

A. D. Sangadzhieva¹, Z. V. Bakaeva², S. Tani³, T. Tanaka³, L. A. Andreeva⁴, N. F. Myasoedov⁴

¹Human and Animal Phisiology, Lomonosov Moscow State University, ²Pirogov Russian National Research Medical University, Moscow, Russian Federation, ³Josai University, Sakado, Japan, ⁴Institute of Molecular Genetics RAS, Moscow, Russian Federation

Contact E-mail Address: annasangadzhieva@gmail.com

Introduction: Glyprolines are family of regulatory peptides. PGP reduces ulcer formation and accelerates ulcer healing by altering cytokine gene expression of blood mononuclear cells. Cytokines are important regulators of inflammation.

Aims & Methods: To study the effect of Pro-Gly-Pro (PGP) and N-acetyl-Pro-Gly-Pro (AcPGP) on the cytokine level in the serum after the acetate ulceration with/without systemic inflammation. Experiments were carried out on male white outbred rats (250-300g). In the first series of experiments, acetate ulcer was caused by applique of acetic acid on the serosa of the stomach by the method of Okabe, in the second series - intraperitoneal injection of LPS and the acetate ulceration. Intranasal injection of peptides (3.7 µmol/kg/40µl, i/n) or saline solution was added during 1-3^d or 4-6^th days after the acetate ulceration. Blood was collected from the jugular vein of the rats to determine the production of IL-1α, -17α, -4, IFNγ, MCP-1 and TNFα in the serum by means of flow cytometry.

Results: The area of ulcers (AU) on the 4^th and 7^th days in the first control group averaged 89.8 ± 15.1 mm² and 39.2 ± 6.4 mm², respectively. PGP reduced the AU significantly on the 4^th and the 7^th days namely by 80.9% and 87.5%, respectively. The antiulcer effect of AcPGP on the 7^th day was equal to 76.0%. The AU on the 4^th and 7^th days was 33.8 ± 6.5 mm² and 42.7 ± 4.3 mm² in the second control group. PGP reduced the ulcers by 57.7% and 41.2% to the 4^th and the 7^th days, respectively. AcPGP had only the tendency to reduce it.

The concentrations of IL-1α and MCP-1 in the serum of the first intact group were 61.9 ± 15.1 pg/ml and 537.2 ± 82.2 pg/ml, respectively. In the second intact group the concentrations of IL-1α and MCP-1 were 718.7 ± 26.0 pg/ml and 803.9 ± 4.6 pg/ml. Other cytokines (CK) in rats of both groups were in minimum quantities (<10 pg): TNFα, IFNg and IL-17α.

The acetate ulceration in the first control group has induced a significant increase of IL-1α and MCP-1 on the 4^th day in the serum in 2.2 and 13.5 times, respectively. The level of the other CK has not changed. On the 7^th day the concentration of IL-1α and MCP-1 has been increased. PGP has not affected on the level of elevated cytokines by the acetate ulceration the in the serum of rats. AcPGP has reduced the value of IL-1α in the serum of 37.2% and 41.7% on the 4^th and 7^th day after the acetate ulceration, respectively, and on the 4^th day MCP-1 by 20.4% vs control.

The acetate ulceration in the serum of the second control group on the 4^th and 7^th days, on the contrary, has caused a significant decrease in IL-1α in 2.9 and 2.6 times, respectively. The level of the other CK has not changed. The peptides, PGP and AcPGP have reduced the production of IL-1α by 58.1% and 64.2% on the 4^th day vs control, respectively. On the 7^th day the changes were minor. The content of MCP-1 in the serum of all groups has remained high.

Conclusion: 1. Development of the acetate-induced ulcers in rats is accompanied by a significant increase in serum IL-1α and MCP-1. AcPGP inhibits IL-1α and MCP-1 in the serum on the 4^th day and on the 7^th day only IL-1α.

2. PGP and AcPGP reduce the production IL-1α on the background of systemic inflammation and acetate ulceration to the 4^th day.

Disclosure of Interest: None declared

P0469 OXYNTIC GASTRIC ATROPHY IN AUTOIMMUNE GASTRITIS COMPARED TO HELICOBACTER PYLORI GASTRITIS

M. Venerito¹, M. Varbanova¹, F.-W. Röhl², D. Reinhold³, K. Frauenschläger⁴, J. Weigt¹, A. Link¹, P. Malfertheiner¹

¹Dept. of Gastroenterology, Hepatology and Infectious Diseases, ²Institute for Biometrics and Medical Informatics, ³Institute of Molecular and Clinical Immunology, ⁴Institute of Pathology, Otto-von-guericke University, Magdeburg, Germany

Contact E-mail Address: m.venerito@med.ovgu.de

Introduction: Severe oxyntic gastric atrophy (OGA) is the classical phenotype of autoimmune gastritis (AIG) and occurs in a small subset of patients with H. pylori gastritis as well.

Aims & Methods: To assess characteristics of advanced (moderate to severe) OGA in AIG compared to advanced OGA as a consequence of H. pylori infection. Patients presenting for esophagogastroduodenoscopy (EGD) from July 2011 to October 2014 were prospectively included (N=452). Gastric biopsies were obtained for histological analysis and H. pylori testing. Serum gastrin-17 (G17), pepsinogen (PG) I, PGII and antibodies against H. pylori and CagA were determined in all patients. In patients with advanced OGA, antibodies against parietal cells and intrinsic factor were also determined. Demographics, medical history, and current medication were recorded. Areas under the curves (AUCs) were calculated for serum biomarkers and compared to histology.

Results: Overall, 34 patients had advanced OGA by histology (22 women, age 61 ± 15, range 23-86). Current or past H. pylori infection and AIG were present in 14/34 and 22/34 patients, respectively. H. pylori-negative AIG patients (N=18) were more likely to have another autoimmune disease (OR 18.8; 95%CI 2.0-173.9), severe corpus atrophy (OR 10.3; 95%CI 1.8-60.5), and corpus intestinal metaplasia (OR 37.4; 95%CI 3.8-364.6). The performance of G17, PG I and PGI/II was outstanding for AIG patients (AUC=0.81, 0.95 and 0.96, respectively), but average for H. pylori positive patients with advanced OGA (AUC=0.68, 0.77 and 0.73, respectively).

Conclusion: H. pylori-negative AIG has a distinct clinical, morphological and serological expression compared to advanced OGA in H. pylori gastritis.

Disclosure of Interest: None declared

P0470 EFFECT OF PGP AND N-ACETYL-PGP ON CON A-STIMULATED CYTOKINE PRODUCTION BY LYMPH NODES GASTRICUS CAUDALIS CELLS IN RATS ON THE BACKGROUND OF SYSTEMIC INFLAMMATION AND ACETATE ULCERATION

Z. V. Bakaeva¹, J. L. Wallace², A. D. Sangadzhieva³, S. I. Pavlova⁴, I. G. Kozlov¹

¹Pirogov Russian National Research Medical University (RNRMU), Moscow, Russian Federation, ²University of Calgary, Alberta, Canada, ³Lomonosov Moscow State University, Moscow, ⁴Ulyanov Chuvash State University, Cheboksary, Russian Federation

Contact E-mail Address: zv.bakaeva@gmail.com

Introduction: Lymphocytes of regional lymph nodes are the main sources of cytokines which are involved in inflammation. Lymph node gastricus caudalis (ln. gastricus caudalis) is adjacent to gastroepiploic vein and drains the rat stomach through lymph vessels. Collagen hydrolysis in inflammation leads to the formation of glycine- and proline-containing peptides. PGP reduces the development and accelerates healing of the acetate ulcer.

Aims & Methods: The aims of this study were to examine the effects of Pro-Gly-Pro (PGP) and N-acetyl-Pro-Gly-Pro (AcPGP) on Con A-stimulated cytokine secretion by cells of ln. gastricus caudalis in rats on the background of systemic inflammation (SI) and acetate-induced ulceration. Acetate ulcer (AU) caused by the S. Okabe method with modifications (1971). To create SI in rats with/without ulcer was used i.p. injection LPS. Cells of ln. gastricus caudalis (10⁶/well) were cultured in the presence of the mitogen Con A and peptide PGP/AcPGP (10⁻⁵ M). The supernatant was collected after 24 and 48 hours after cell seeding and the cytokines was determined by flow cytometry.

Results: The peak values of IL-1α, MCP-1, IL-17α, IFNg, IL-4 and TNFα accounted for 48 h and were equal in intact cells ln. gastricus caudalis 23.8 ± 4.4, 6.0 ± 1.1, 500.8 ± 85.3; 566.0 ± 139.8, 55.6 ± 6.5, 59.2 ± 15.7 pg/ml respectively. On the background of SI secretion IL-1α, MCP-1, IL-17α, IFNg and IL-4 was 1.8, 1.5, 2.0, 1.5 and 12 times less respectively, TNFα was not detected.

On the 4th day after AU induction with SI cells of ln.gastricus caudalis produced IL-1α, IFNγ, IL-4 in 2.2, 2.5, 1.4 times more and MCP-1, IL-17α in 1.7, 1.5 times less respectively, than the same cells but without ulcers. It should be noted that in these cells the secretion of IL-1α, IL-17α, IFNγ was respectively in 2.3, 1.8, 4.6 times greater, and MCP-1 was less in 1.9 times than comparison with cells after AU formation, but without SI. On the 7th day after AU induction with SI secretion of MCP-1 and IL-17α increased almost 4.0 times. The values of IL-1α and IFNγ have not changed. IL-4, on the contrary, decreased by 1.7 times. TNFα production was very low.

On the 4th day of AU with SI the PGP reduced production of IFNγ and IL-4 respectively in 3.3 and 3.1 times vs control. The AcPGP reduced production on the 7^th day IFNg and IL-4 respectively in 2.1 and 2.2 times vs control. Both peptides significantly reduced IL-17α production. IL-1α and MCP-1 showed no significant changes.

Conclusion: On the 4^th day after the AU induction with SI increased secretion of IL-1α, IFNγ, IL-4 and reduced IL-17α and MCP-1 by cells of ln. gastricus caudalis was observed. While AU formation without SI was accompanied by an acute shortage of all these cytokines. PGP reduces AU formation and cell ln.gastricus caudalis production of IFNγ, IL-4 on the background of SI. On the 7^th day after the AU on the background of SI there was significant increase of MCP-1 and IL-17α and decreased production of IL-4, which is accompanied by an even greater development of ulceration, whereas without SI on the 7^th day usually there was a gradual ulcer healing. PGP accelerated ulcer healing by modulation of IL-17α.

Disclosure of Interest: None declared

P0471 THE RISK OF GASTROINTESTINGAL BLEEDING WITH NOVEL ORAL ANTICOAGULANTS IN A LARGE COHORT OF PATIENTS AT A DISTRICT GENERAL HOSPITAL

A. Kumar¹, B. Disney¹, R. Hipkins², S. Hughes², S. Ishaq¹, S. Jenkins²

¹Gastroenterology, ²Haematology, Russells Hall Hospital, Birmingham, United Kingdom

Contact E-mail Address: aditikumar@nhs.net

Introduction: Rivaroxaban, apixaban and dabigatran are novel oral anticoagulants (NOAC). NOACs have been used as first line treatment for atrial fibrillation since November 2012 and for VTE since December 2013. The trial data regarding the risk of gastrointestinal (GI) bleeding has been conflicting, although a meta-analysis found an increased risk of GI bleeding with NOACs as opposed to warfarin (2.3% versus 1.3%)¹. However, little is known about the incidence of GI bleeding in the real-world setting. We aimed to evaluate the incidence of GI bleeding, endoscopic findings, time of onset of bleeding and the need for intervention in patients taking NOACs in our institution.

Aims & Methods: We performed a retrospective review of all patients at Russells Hall Hospital who received NOACs. These patients were identified from the anticoagulation database and cross-referenced with the GI database and patient notes. Basic demographic, clinical and laboratory data and endoscopic findings were collated.

Results: A total of 2490 patients were identified to be on NOACs, of which 64 were found to have an episode of GI bleeding. In this cohort of patients, this gives an incidence of 2.57%. 57 of 2337 patients were on rivaroxaban, 3 of 77 on apixaban and 4 of 76 on dabigatran with an incidence of GI bleeding of 2.4%, 3.9% and 5.3% respectively. There was a greater incidence found with females than males (55% vs. 45%) with the median age 79.6 years (range 53-95). The 30-day mortality rate was 10.9% (n=11). The causes of death were stated as metastatic carcinoma (3), sepsis (3), pneumonia (2), and unknown (3).

Of these 64 patients, clinically 33 (51.6%) had an upper GI bleed (UGIB) and 31 (48.4%) had a lower GI bleed (LGIB). The median time from starting NOAC to having a GI bleed was 6.7 months (range 2 days-19.7 months). Endoscopy results were varied with the most common findings being haemorrhoids (15%), diverticular disease (14%), normal findings (11.8%), polyps (10.8%), peptic ulcer disease (9.7%), gastritis (8.6%), and other (30.1%). 9 patients (14%) required endoscopic intervention and 23 patients (35.9%) required the use of blood products. As compared to LGIB patients, UGIB patients required greater frequency of endoscopic intervention (15% versus 12.9%), were more likely to be inpatients (97% versus 35%) with a greater drop in haemoglobin (median Hb at presentation: 82 g/L versus 105 g/L) and increased use of blood products (55% versus 16%).

Conclusion: Although the results from our cohort of patients show a higher incidence of GI bleeding of 2.57% as compared to that observed in previous studies (2.3%), there were no deaths directly related to the bleeds, only 14% required endoscopic intervention and the use of blood products was relatively low at 35.9%. Whilst the incidence of GI bleeding is lower for rivaroxaban than apixaban and dabigatran, the data for the latter two is much smaller and thus further studies are needed to make a true comparison between the three NOACs.

Disclosure of Interest: A. Kumar: None declared, B. Disney: None declared, R. Hipkins: None declared, S. Hughes: None declared, S. Ishaq: None declared, S. Jenkins Lecture fee(s): Received payments for speaking from Bayer

P0472 ENDOSCOPIC VARICEAL LIGATION FOLLOWED BY ARGON PLASMA COAGULATION VERSUS ENDOSCOPIC VARICEAL LIGATION ALONE: A RANDOMIZED CONTROLLED TRIAL

A. A. Abd Elmoety¹, Y. Hamza², A. Zeid¹, A. Kamal¹

¹Internal Medicine, Hepatology Unit, ²General Surgery Department, Head and Neck Unit, Faculty of Medicine, Alexandria University, Alexandria, Egypt

Contact E-mail Address: ahmed.kamal.med.scientific@gmail.com

Introduction: After the first attack of acute variceal hemorrhage patients have a very high risk of recurrent variceal bleeding and death. Rebleeding rates after endoscopic variceal ligation (EVL) are high, thus current recommendation is to combine non selective beta-blockers (NSBB) to EVL but side effects and relative contraindications to NSBB are common and hinder treatment or require discontinuation in 15-20% of cirrhotic patients. Induction of fibrosis of distal esophageal mucosa using argon plasma coagulation (APC) may suppress capillary proliferation and invasion of perforating veins thus decreasing esophageal varices (EV) recurrence.

Aims & Methods: This study included 40 subjects with post viral liver cirrhosis and previous history of upper gastrointestinal bleeding. They were submitted for EVL and obliteration of varices. Then patients were randomly assigned to either APC (group 1) or just observation (group 2).

Results: During 2 years follow up 20% of subjects in group 1 experienced EV recurrence but no one needed rebanding. In group 2, 68.4% experienced EV recurrence (p=0.002) and 63.2% underwent rebanding (P < 0.001). (Figure) No subject in group 1 experienced rebleeding during the 2 year follow up, while 10.5% of subjects in group 2 experienced rebleeding from EV (p=0.231). No subject in both groups showed development of gastric varices. 3 subjects in group 1 and 4 subjects in group 2 showed development of new severe portal hypertensive gastropathy (p=0.695). One subject in group 2 (5.3%) experienced bleeding from severe portal hypertensive gastropathy during the 2 year follow up while no subject in group 1 experienced this (p=0.487).

Conclusion: APC can decrease the risk of recurrence, the need for rebanding of EV and the frequency of endoscopic follow up after EVL. APC after EVL may be recommended in secondary prophylaxis against esophageal variceal bleeding especially in those who have contraindications, intolerant or incompliant to NSBB.

Disclosure of Interest: None declared

P0473 USEFULNESS OF THE NASOGASTRIC LAVAGE BEFORE EMERGENCY ENDOSCOPY IN THE PATIENTS WITH NON-VARICEAL UPPER GI BLEEDING

A. Ono¹, H. Hata¹, M. Toki¹, H. Mori¹, T. Hisamatsu¹, S. Takahashi¹

¹The Third Department of Internal Medicine, Kyorin University Hospital, Mitaka-city, Japan

Contact E-mail Address: akiko@orangejp.com

Introduction: Before treating emergency department patients with hematochezia, melena or hematemesis, it is important to predict the presence and location of a bleeding source. Moreover, fine visual field is necessary to find a bleeding point and achieve prompt hemostasis in emergency endoscopy. In Japanese clinical practice, nasogastric lavage is often performed before emergency endoscopy for gastrointestinal hemorrhage. However, it is not clear whether nasogastric lavage before emergency endoscopy is useful.

Aims & Methods: We estimate the validity of nasogastric lavage before endoscopy in emergency department patients with non-variceal upper GI bleeding. From May 2011 to January 2014, 92 patients with hematochezia, melena or hematemesis underwent emergency endoscopy (within 24 hours from onset) in Kyorin University Hospital. In 60 patients nasogastric lavage was performed (500-2000ml) before endoscopy (group A), and in 32 patients nasogastric lavage was not performed (group B). We retrospectively reviewed their medical records to analyze the following factors: age, sex distribution, systolic blood pressure and interval from onset to endoscopy, nasogastric lavage findings (bloody, “coffee ground”, clear/bile), a vision score of the endoscopic field (1: No need to wash, 2: The fold of gastric greater curvature hidden, 3: Gastric fundus full of residue and blood, 4: Gastric angle not visible), detection of bleeding points, procedural time for treatment, duration of hospitalization, the success rate of endoscopic hemostasis, rebleeding rate and complications associated with nasogastric lavage.

Results: Between group A and B, there was no significant difference in mean age, sex distribution, systolic blood pressure and interval from onset to endoscopy. And the blood test of hemoglobin, serum albumin level and blood urea nitrogen on admission were also no significant difference between group A and B.

There were 48 bleeding points in group A (60) and 26 in group B (32), and the rate of bleeding point was the same (80%). In group (A), 35 bleeding points (97.2%) were detected out of 36 bloody lavage findings, and 8 bleeding points (88.9%) were detected out of 9 “coffee ground” lavage findings. On the other hand, only 5 lesions (33.3%:1 angioectasia/4 duodenal ulcer) were detected out of the 15 patients with clear/bile lavage findings.

An average of vision score (1.85 vs 1.88, p=0.89) and the success rate of endoscopic hemostasis (91.7% vs 96.2% p=0.80) was not significantly different between the two groups. The rate of rebleeding or conversion to transcatheter embolization were not significantly different between the two groups (rebleeding 4.2% vs 3.8% p=0.52, transcatheter embolization 4.2% vs 0.0% p=0.76). And the duration of hospitalization also did not differ between the two groups (19.7days vs 22.3 days p=0.70). There was no complication associated with nasogastric lavage.

Conclusion: Nasogastric lavage before emergency endoscopy may be useful in predicting the presence of bleeding resources. However, it did not lead to the improvement of clinical outcomes, such as the success rate of endoscopic hemostasis, and the rate of rebleeding or conversion to transcatheter embolization and the duration of hospitalization.

Disclosure of Interest: None declared

P0474 PREDICTION OF CLINICAL OUTCOME OF ACUTE VARICEAL BLEEDING. DO WE NEED A RISK SCORING SYSTEM?

A. M. Zaghloul¹, G. M. Galal¹, M. Saif Alislam¹, M. Zaki¹

¹Tropical Medicine and Gastroenterology, Sohag Faculty of Medicine, Sohag, Egypt

Contact E-mail Address: amrmoh_80@yahoo.com

Introduction: Variceal bleeding is the most common cause of acute upper gastrointestinal bleeding in Egypt and its management represents a significant economic burden. There are only few inconsistent reports on the incidence and prediction of outcome of acute variceal bleeding in Egypt. Admission Rockall Score (RS), full RS, and Glasgow-Blatchford Score (GBS) can all be used to stratify the risk but to our knowledge no studies were done to compare between them in prediction of outcome in variceal bleeding in our country.

Aims & Methods: To compare both admission and full RS and GBS in predicting outcomes in variceal bleeding patients in Upper Egypt. A total of 120 patients with variceal bleeding were enrolled in the study.

Patients were followed up 30 days after admission to emergency department to determine cases of rebleeding or death during this period. By using areas under the curve (AUC), we compared the 3 scores in terms of identifying the most predictive score of unfavourable outcome

Results: Rebleeding rate was 15% (18 patients), mortality rate was 14.7% (17 patients), transfusion was needed in 72 patients (60%). For prediction of rebleeding Blatchford score had the highest specificity 68.6% and the highest sensitivity 72.2% (AUC, 0.71) and it was superior to both the full RS (AUC, 0.67), and admission Rockall score (AUC, 0.60). Full Rockall score had the highest specificity 87.5%, (AUC, 0.79)in prediction of death and it was superior to both the admission RS (AUC, 0.72), and Blatchford score (AUC, 0.66). GBS had the highest specificity 75.0% and the highest sensitivity 66.7% (AUC, 0.76) in detecting patients who needed transfusion, it was superior to both the full RS (AUC, 0.57), and admission RS (AUC, 0.55).

Conclusion: Galasgow Blatchford score can be used to predict rebleeding and need for transfusion in patients with variceal bleeding while Full Rockall score was the most accurate score that predicted mortality risk in these patients

Disclosure of Interest: None declared

P0475 COMPARISON OF RISK SCORING SYSTEMS IN PREDICTING CLINICAL OUTCOME OF UPPER GASTROINTESTINAL BLEEDING SECONDARY TO PEPTIC ULCER DISEASE

A. G. Antunes¹, M. Eusébio¹, A. Vaz¹, P. Queirós², T. Gago¹, B. Peixe¹, H. Guerreiro¹

¹Gastroenterology department, Centro Hospitalar do Algarve, Faro, ²Gastroenterology department, Centro Hospitalar do Algarve, Portimão, Portugal

Contact E-mail Address: sergiogiao@hotmail.com

Introduction: Upper gastrointestinal bleeding (UGIB) secondary to peptic ulcer disease (PUD) is still a life-threatening condition and one of the greatest challenges in Gastroenterology. Different scoring systems have been developed to identify the patients with higher risk of adverse outcomes.

Aims & Methods: To assess the effectiveness of different scoring systems - Glasgow-Blatchford-Score (GBS), the Baylor College Score (BCS), Rockall Score (RS), Almela Score (AS), Cedars Sinai Score (CSS) – at predicting rebleeding, need for surgery and mortality.

Retrospective review of all UGIB admissions secondary to PUD that required hospitalization, from January 2010 to December 2014. We recorded demographic, clinical and laboratory data and we assessed the different scores and compared them by using areas under the curve (AUCs).

Results: We identified 377 patients, 249 males, with a mean age of 70 years. Duodenum ulcers (57%) were more frequent then gastric ulcers. When analyzed the predictors of recurrent bleeding: 47 patients (13%) presented gastric ulcers along the lesser curvature or duodenal ulcers along the posterior wall of the duodenal bulb; 67% had endoscopic high-risk stigmata for recurrent bleeding (≥Forrest IIB); 54% were described as Large ulcers (>1 cm) on endoscopy.

Rebleeding occurred in 20% of patients, need for surgery in 7% and mortality was 7%.

For the prediction of rebleeding, the scores that showed more discriminating power were AS (AUC: 0.811), CSS (AUC: 0.802) and RS (AUC: 0.743); although AS and CS weren’t statistically different, they were both statistically superior to RS (respectively, p = 0.010 and p = 0.031).

For the prediction of mortality, the scores that demonstrated better discriminating power were RS (AUC: 0.874), the CSS (AUC: 0.869) and the GBS (AUC: 0.856), without statistically significant differences, when compared.

Given the need for surgery, the scores that revealed the highest discriminating power, were AS (AUC: 0.771), the RS (AUC: 0.707) and the CSS (AUC: 0.696); no statistically significant differences were observed when compared.

Conclusion: The set of our results favor the use of CSS and the RS, instead of the other scores, in the prediction of rebleeding, need for surgery, and mortality during hospitalization, with superiority of CSS in the prediction of rebleeding risk.

Disclosure of Interest: None declared

P0476 COMPARISON OF THREE DIFFERENT SCORING SYSTEMS FOR RISK STRATIFICATION IN GERIATRIC PATIENTS WITH ACUTE UPPER GASTROINTESTINAL BLEEDING

Ç. Kalkan¹, F. Karakaya¹, A. Tüzün², Z. B. Gençtürk², I. Soykan²

¹Ankara University, Ankara, Turkey, ²Gastroenterology, Ankara University, Ankara, Turkey

Contact E-mail Address: isoykan@medicine.ankara.edu.tr

Introduction: Acute gastrointestinal bleeding is a potentially life-threatening condition which requires rapid assessment and dynamic management. Several scoring systems have been established to predict mortality and rebleeding.

Aims & Methods: The aim of this study was to compare three different scoring systems in order to predict short-term mortality, rebleeding rate, duration of hospitalization and need for blood transfusion in elderly patients with upper gastrointestinal bleeding. A retrospective analysis was undertaken in 335 elderly patients with upeer gastrointestinal bleeding. The pre and post endoscopic Rockall, Glasgow-Blatchford and AIMS65 scores were calculated, and the association between these scoring systems and patient outcomes such as rebleeding, mortality, and need for blood transfusion were assessed. The area under the receiver operating characteristic curve was calculated to assess the validity of scoring systems in predicting mortality, rebleeding, and duration of hospitalization.

Results: Pre (4.5) and post-endocopic (7.5) Rockall were superior to Glasgow-Blatchford (12.5) in terms of predicting mortality (p=0.006, p=0.015). Likewise, pre (4.5) and post-endoscopic Rockall were superior to Glasgow-Blatchford in terms of predicting rebleeding (p=0.013, p=0.03). There was an association between prolonged hospitalization and mortality. 94% of patients with an average 5 days of hospitalization were alive, while the percentage reduced to 56.1% for 20 days and 20.2% for 40 days.

Conclusion: The Rockall score is clinically useful in predicting mortality and rebleeding compared to Glasgow-Blatchford and AIMS65 systems. However, in predicting duration of hospitalization and need for blood transfusion, Glasgow-Blatchford scoring system was superior to Rockall and AIMS65 in elderly patients with upper gastrointestinal bleeding.

Disclosure of Interest: None declared

P0477 EFFICACY OF ENDOSCOPIC HEMOSTASIS WITH THE ENDOSCOPIC SUBMUCOSAL DISSECTION TECHNIQUE FOR UPPER GASTROINTESTINAL BLEEDING OVER A 12-YEAR PERIOD

D. Yamaguchi¹, R. Shiraishi¹, K. Mannen¹, N. Tsuruoka¹, E. Takeshita¹, T. Yukimoto¹, S. Matsuura¹, T. Morisaki², R. Iwakiri¹, K. Fujimoto¹

¹Department of Internal Medicine and Gastrointestinal Endoscopy, Saga Medical School, Saga, ²Department of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki, Japan

Contact E-mail Address: daisukehawks@gmail.com

Introduction: The endoscopic submucosal dissection (ESD) technique was introduced to obtain en bloc specimens of early gastric cancer. Endoscopic high-frequency soft coagulation is used to manage visible bleeding or nonbleeding vessels during ESD. Upper gastrointestinal bleeding (UGIB) is the most common gastroenterological emergency, and has a considerable morbidity and mortality. Recently, endoscopic high-frequency soft coagulation has been used to establish endoscopic hemostasis in patients with nonvariceal UGIB. This study aimed to compare the aetiology and clinical outcome of nonvariceal UGIB between two periods during the last 12 years.

Aims & Methods: We retrospectively investigated the medical records of 568 patients who underwent emergency endoscopy for nonvariceal UGIB from September 2002 to August 2014. The patients were divided into two periods: the first period was from September 2002 to August 2008 and the second period was from September 2008 to September 2014. We examined the characteristics of these patients and compared the efficacy of endoscopic hemostasis by soft coagulation using the ESD technique and hemoclips. We also compared the rate of endoscopic hemostasis by specialists and by trainees The specialists already had the fundamental skills and knowledge needed for ESD, and each specialist assisted in 40 gastric ESD procedures.

Results: Among the 568 patients with UGIB, 230 were in the first period and 338 patients were in the second period. The ratio of Helicobacter pylori infection was significantly lower in the second period than in the first period (62.8% vs. 77.4%, p < 0.001). The proportion of patients who took antithrombotics did not change between the two periods. Peptic ulcer lesions were the main cause of bleeding (85.2%) during the study period, but bleeding from other lesions, such as esophagitis, increased significantly in the second period (p < 0.001). Endoscopic hemostasis was successfully carried out in 220/230 (95.6%) patients in the first period and in 321/338 (95.0%) patients in the second period, with no significant difference between the periods. There were no differences in the incidence of rebleeding (13.0% vs. 9.1%) and mortality (0.9% vs. 2.7%) between the two periods. In the modality of endoscopic hemostasis, the rate of endoscopic hemostasis by soft coagulation using the ESD technique was significantly higher in the second period than in the first period (77.9% vs. 10.6%, p < 0.001). The rate of endoscopic hemostasis by trainees was significantly higher in the second period than in the first period (75.7% vs. 56.1%, p < 0.001).

Conclusion: Endoscopic hemostasis by soft coagulation using the ESD technique is safe for trainees and effective with UGIB.

Disclosure of Interest: None declared

P0478 EARLY ENDOSCOPY VS URGENT ENDOSCOPY ON EVOLUTION OF PATIENTS WITH PEPTIC ULCER BLEEDING

D. Matei¹², I. Groza², B. Furnea², L. Puie², C. Levi², C. Cruciat², M. Tantau¹²

¹University of Medicine and Pharmacy Iuliu Hatieganu, ²Regional Institute of Gastroenterology and Hepatology, Cluj Napoca, Romania

Contact E-mail Address: dmatei68@gmail.com

Introduction: Acute upper gastrointestinal bleeding is a common medical emergency worldwide and its major cause is peptic ulcer bleeding (PUB). Most therapeutic guidelines recommend performing endoscopy within the first 24 hours (early endoscopy).

Aims & Methods: The aim of the study is to evaluate the influence of time interval to perform endoscopy (endoscopy timing) on mortality rate, re-bleeding rate, needs of surgery, needs of transfusions and hospitalization time.

It is a prospective study done in a tertiary medical service with permanent access to Endoscopy Department, for 8 months interval (between November 2012 and July 2013). 201 patients with peptic ulcer bleeding were included in the study. The endoscopy was performed within the first 24 hours in all patients. The patients were followed the whole duration of hospitalization. Based on endoscopy timing the patients were divided into 2 groups: urgent endoscopy (UE) (within 3 hours) and early endoscopy (EE) (3-24 hours).

Results: In the studied group of 201 patients, 112 of them had UE (55.7%), while 89 had EE (44.3%). The mean age was 62.6 years (min 19 years, max 94 years), with a predominance of male patients (68.7%).

Mortality rate was 9.5%, it was 11.6% in patients with UE compared with 6.7% in patients with EE (p=0.35).

Re-bleeding occured in 8% of the paientes, it was more frequent in UE group compared to EE patients (11.6% vs 3.4%), but the difference was without statistical difference (p=0.06).

Surgery was needed in 4% of the patients, with a higher rate in patients with UE than patients with EE (6.3% vs 1.1%) (p=0.14).

The average need of transfusions was higher in UE group compared to EE group (2.29 vs 1.69 blood units), without statistical significance (p=0.08).

Even the hospitalization period is slighty prolonged in patients with EE vs UE group (8.26 days vs 7.27 days), this was not significantly influenced by the endoscopy timing (p=0.33).

Conclusion: Urgent endoscopy compared to early endoscopy has not been significantly superior regarding the mortality rate, re-bleeding episodes, needs for surgery, needs of transfusions and hospitalization period in patients with UGIB.

Disclosure of Interest: None declared

P0479 PROLONGED GASTROINTESTINAL TRANSIT IS PRESENT IN TYPE 1 DIABETES MELLITUS PRIOR TO THE DEVELOPMENT OF SYMPTOMS

C. Brock¹, A. D. Farmer¹, A. G. Pederson¹, B. Brock², A. M. Drewes¹

¹Mech-Sense, Aalborg University Hospital, Aalborg, ²Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark

Contact E-mail Address: a.farmer@qmul.ac.uk

Introduction: The wireless motility capsule (WMC) is a minimally invasive ambulatory technology that concurrently measures intraluminal pH, temperature and pressure as it traverses the gastrointestinal (GI) tract. Knowledge gaps remain concerning regional GI transit times with type 1 diabetes mellitus (T1DM) with established sensory neuropathy. Moreover, pH drop across the ileocaecal valve (ICV) has been recently proposed as a surrogate biomarker for bacterial fermentation in the caecum.

Aims & Methods: 24 patients with T1DM (17 male, mean age 54 years, range 36-66), with confirmed sensory neuropathy but no GI symptoms, and 22 healthy controls (17 male, mean age 54 years, range 38-72) ingested a WMC together with a standardized meal. Gastric emptying time (GET), small bowel transit time (SBTT), colon transit time (CTT) and whole gut transit time (WGTT) and pH drop across the ICV were calculated using the WMC.

Results: In patients with T1DM, GET (350 minutes ±65.8 vs. 206 ±11.8, p=0.05), CTT (2188 minutes ±235 vs. 1302 ±155, p=0.004) and WGTT (2831 minutes ±271 vs. 1893 ±199, p=0.009) was longer in comparison to healthy controls. pH drop across the ICV was higher in T1DM patients when compared to controls (−1.73 ±0.4 vs. −1.3 ±0.5, p=0.005) and was associated slower CTT (r=−0.6, p=0.002). Multivariate linear regression, controlling for age, gender and glycaemic control were not associated with changes in regional or whole gut transit times.

Conclusion: In patients with T1DM with sensory neuropathy, but without GI symptoms, GET, CTT and WGTT are prolonged in comparison to controls and had a larger pH drop across the ileocaecal valve suggesting heightened caecal fermentation. Whether changes in the microbiota contribute to such changes in transit times in T1DM warrants further study as it may represent a potential therapeutic target prior to the development of symptomatic dysmotility.

Disclosure of Interest: None declared

P0480 ACHALASIA IN CHILDREN: COMPARISON BETWEEN THE IDIOPATHIC AND THE GENETIC FORM

A. Tebaibia¹, M. E. A. boudjella¹, N. oumnia¹, M. Boucelma¹

¹Internal Medicine, Kouba Hospital, Algiers, Algeria

Contact E-mail Address: tebaibia@hotmail.com

Introduction: Achalasia is a primary esophageal motor disorder rarely observed in children. It is most often isolated and called idiopathic achalasia or exceptionally associated with a genetic disorder.

Aims & Methods: To compare the epidemiological, clinical and paraclinical characteristics in the two entity.

This is a prospective study of 116 consecutive children (M : 62 (53%), F :54 (47%), mean age :10± 4 yrs ; range : 3 months -16 years) enrolled over a period of 24 years (1992-2014). All children underwent a complete clinical check up, an ophthalmologic check up with a Schirmer test, an adrenal hormone balance, an esophageal barium swallow, an upper endoscopy and an esophageal manometry. a neurological examination and EMG were performed in case of suspicion of Allgrove syndrome.

Results: Achalasia was isolated (group I) in 64 cases, it was associated to Allgrove syndrome (group II) in 52 cases. 3A syndrome (alacrima, achalasia, adrenal insufficiency) was observed in 36 cases, 2A syndrome (alacrima, achalasia) in 13 cases and 4 A syndrome (alacrima, achalasia, adrenal insufficiency, autonomic neuropathy) in 3 cases. The comparison between the two groups (Table 1) showed a significant differences between children in both groups. Two (4%) deaths, caused by acute adrenal insufficiency, were recorded in group II.

Table-1.

	Isolated achalasia Group I : (n = 64)	Allgrove syndrome Group II : (n = 52)	P
Mean age (year)	11 ± 4.2	8 ± 5	<0.001
Consanguinity	0%	75%	-
Backwardness	13%	35%	<0.001
Chest pain	23%	0%	<0.01
Familial achalasia	0%	43%	<0.001
Growth retardation	13%	65%	<0.001

Conclusion: Achalasia in children is frequently associated with Allgrove syndrome. Consanguinity, backwardness, growth retardation and familial form are almost found in Allgrove syndrome. Prognosis is related to the acute adrenal insufficiency.

Disclosure of Interest: None declared

P0481 RELIABILITY OF A SINGLE MULTIPLE RAPID SWALLOWING SEQUENCE DURING HIGH RESOLUTION MANOMETRY

A. Mauro¹, A. Elvevi¹, D. Consonni², M. Franchina¹, D. Pugliese¹, A. Tenca¹, D. Conte¹, R. Penagini¹

¹Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico and Università degli Studi of Milan, ²Epidemiology Unit,, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico and Università degli Studi of Milan, Milan, Italy

Contact E-mail Address: aurelio.mauro88@gmail.com

Introduction: Low (10ml) and/or high (200ml) volume multiple rapid swallowing (MRS) have been proposed as additional tests during oesophageal high resolution manometry (HRM) in order to assess pathophysiological alterations of clinical significance. Reproducibility of these tests has however been little explored, although, for low volume MRS, one report has suggested that a single sequence provides reliable information¹.

Aims & Methods: To assess concordance of two sequences of both 10 and 200 ml MRS in patients referred for HRM. Achalasia patients were excluded. One hundred and nine consecutive patients performed the two sequences for both tests, however only 91 of them (35 men, 48; 28-74 yrs) performed them adequately and were included in the study. Nineteen healthy volunteers (7 men, 28;23-33 yrs) provided the normal range of the following MRS related variables, which have been evaluated: 1) presence of motor inhibition, i.e. no pressure wave > 20mmHg in the distal oesophageal body during MRS; 2) oesophago-gastric pressure gradient (OGPG) in the last 5s of MRS, as a measure of resistance to outflow; 3) 4s integrated relaxation pressure (4sIRP); 4) presence of after contraction, i.e. wave of > 20 mmHg in the distal oesophageal body; 5) ratio between the distal contractile integral (DCI) of the identified after-contraction and the mean DCI of 10 single water swallows (MRS/SS DCI ratio), as a measure of motor reserve.

Results: Descriptive data and concordance between values of the two sequences, evaluated with Lin concordance correlation coefficient², are shown in table 1*. Concordance of the two sequences as to being inside or outside of our normal range was evaluated with kappa coefficient and was moderate to substantial for presence of motor inhibition, OGPG and 4s IRP during 10 ml MRS (k: 0.50, 0.78, 0.77 respectively) and 200 ml MRS (k: 0.52, 0.56, 0.63 respectively), but was disappointingly low for presence of after contraction wave and MRS/SS DCI ratio after 10 ml MRS (k: 0.28, 0.10 respectively) and 200 ml MRS (k: 0.31, 0.20 respectively).

* Lin coefficient not applicable for presence/absence of motor inhibition and after contraction as they are a nominal variable.

Table. 1.

Descriptive data expressed as Median (IQ range) and Lin concordance correlation coefficient between the first and the second multiple rapid swallowing (MRS).

	10 ml MRS		Lin	200 ml MRS		Lin
	1st	2nd		1st	2nd
OGPG (mmHg)	1 (−1 to 4)	1 (−1 to 4)	0.81	2 (1 to 5)	2 (0 to 4)	0.75
4s IRP (mmHg)	2.5 (0.6-5.2)	2.1 (0.6-4.7)	0.89	2.5 (0.7 – 5.2)	2.4 (0.2 – 5.0)	0.81
MRS/SS DCI ratio	1.3 (0.8 – 1.9)	1.4 (0.6 – 2.1)	0.54	0.7 (0.4-1.2)	1.0 (0.4 – 1.8)	0.01

Oesophago-gastric pressure gradient (OGPG), 4 second Integrated Relaxation Pressure (4s IRP), Multiple rapid swallowing/single swallow Distal Contractile Integral (MRS/SS DCI).

Conclusion: Inhibitory and resistance variables during low and high-volume MRS are reproducible, whereas strength of the after contraction is not. One sequence of MRS is not enough in order to evaluate the motor reserve; the optimal number of sequences needs to be determined.

Disclosure of Interest: None declared

P0482 MANOMETRIC CHANGES ASSESSED BY HIGH RESOLUTION MANOMETRY BEFORE AND AFTER LUNG TRANSPLANTATION

C. Ciriza De Los Ríos¹, F. Canga¹, I. Castel¹, G. Castellano¹

¹Gastroenterology, Hospital 12 De Octubre, Madrid, Spain

Contact E-mail Address: constanzacarpa@gmail.com

Introduction: Lung transplantation (LTx) is a good choice in most patients with end-stage lung diseases. Gastroesophageal reflux (GER) is associated with LTx rejection and can also impair the esophageal motility. However, is not very well known if other esophageal motor disorders (EMD) can also be contributed to LTx rejection. High resolution manometry (HRM) allowed a better characterization of EMD, upper esophageal sphincter (UES) and esophagogastric junction (EGJ).

Aims & Methods: To determine pre-transplant EMD and changes in esophageal motility observed after LTx. Observational cross-sectional study. 47 consecutive patients in which HRM (Manoscan; Given) was performed prior to LTx and six month after.

Results: Patients' characteristics and manometric parameters are expressed in the table. EMD were found in 36.2% and 44.7% of the patients before and after LTx respectively. There were no differences between lung disease, EGJ abnormalities and EMD before LTx (p=0.189 and p= 0.372; respectively). Neither between lung disease and EGJ diagnosis after LTx (p=0.664) but more esophageal dysmotility was observed after LTx (p=0.021). There were no differences between the LTx type and EGJ abnormalities (p=0.064) and EMD (p=0.994). No differences were found in the EGJ diagnosis before and after LTx (p=0.387), although EGJ morphology changed pre and post LTx (p=0.025) as 38.3% had EGJ disruption before LTx compared to 17% after. Although there was no significant change in esophageal diagnosis pre and post LTx (p=0.082), more EMD was observed after LTx at the expense of hypercontractile esophagus (1 (2.1%) pre LTx and 9 (19.1%) post LTx). There were no differences in the UES (p=0.506).

Abstract number: P0482

Clinical data	Before LTx	After LTx
Age	53.6 (50.6-56.6)	55 (51.9-58.1)	P < 0.001
Sex (Male)	30 (63.8%)	30 (63.8%)
BMI	24.3 (23.2-25.4)	23.7(22.6-24.9)	0.101
Abdominal perimeter	93.8 (89.1-98.5)	92.5 (87.8-97.2)	0.089
LTx indication COPD Emphysema Cystic fibrosis Scleroderma Pulmonary hypertension Bronchiectasis Fibro emphysema Idiopathic pulmonary fibrosis Histiocytosis Other	3 (6.4%) 12 (25.5%) 3 (6.4%) 1 (2.1%) 7 (14.9%) 1 (2.1%) 3 (6.4%) 13 (27.7%) 1 (2.1%) 3 (6.4%)
LTx type Bilateral Right lung Left lung	30 (63.8%) 12 (25.5%) 5 (10.6%)
LTx rejection NoAcute Chronic		34 (72.3%) 9 (19.1%) 4 (8.6%)
HRM Parameter	Before LTx	After LTx	p-value
LES pressure (mmHg)	13.4 (10.8-15.9)	18.4 (15.1-21.6)	0.001
IRP-4s (mmHg)	8.2 (6.3-10.1)	7.9 (6.4-9.4)	0.808
EGJ total length	3.9 (3.7-4.2)	3.7 (3.5-3.8)	0.011
EGJ abdominal length	2.1 (1.9-2.3)	2.2 (2.1-2.4)	0.582
EGJ thoracic length	1.8 (1.6-2)	1.4 (1.3-1.6)	0.003
esophageal length	24.9 (23.8-26)	25.1 (24.6-25.7)	0.642
DCI	1945.7 (1483.9-2407.5)	3907.4 (2715.4-5099.3)	< 0.001
CFV	4.5 (3.8-5.2)	6.6 (2.4-10.8)	0.349
Distal latency	6.2 (5.6-6.8)	6.9 (6.6-7.3)	0.036
IBP	19 (14.3-23.7)	20.7 (17.2-24.1)	0.116
UES pressure	74.7 (66.5-82.9)	62.4 (54.6-70.3)	0.011

Conclusion: Patients who are candidates for LTx had a high frequency of esophageal motor dysfunction. HRM changes were observed after LTx presenting more frequently higher LES pressure and hypercontractile disorder. These findings might be caused by indirect vagal nerve injury within the surgery.

Disclosure of Interest: None declared

P0483 EFFECT OF AZITHROMYCIN ON ESOPHAGEAL HYPOMOTILITY (EH) AND PREDICTION OF RESPONSE BY OESOPHAGEAL STIMULATIONS TESTS DURING HIGH RESOLUTION MANOMETRY

D. Sifrim¹, J. Jafari¹², E. Yazaki¹, T. Wong², P. Woodland¹

¹Barts and The London School of Medicine and Dentistry, Queen Mary University of London, ²Guys and St Thomas' NHS Foundation Trust, London, United Kingdom

Contact E-mail Address: d.sifrim@qmul.ac.uk

Introduction: Patients with ineffective esophageal contractions and/or fragmented peristalsis during HRM are considered to have esophageal hypomotility (EH). Esophageal hypomotility is due to neural and/or muscular function impairment. In healthy subjects, esophageal stimulation tests like Multiple Rapid Swallows (MRS), increased outlet resistance at GEJ with abdominal compression (AC) and bread swallows (BS) trigger higher amplitude esophageal contractions, unravelling a “contractile reserve capacity” in the esophageal body. The response to these tests in patients with significant EH is unknown, and probably depends on severity and reversibility of neuro-muscular dysfunction. Prokinetic drugs have been used to treat HH with inconsistent results. Azithromycin (AZI) is a macrolide antibiotic with similar prokinetic effects as erythromycin, with fewer side effects and less tachyphylaxia.

Aims & Methods: We aimed to assess the effect of AZI in patients with EH and the ability of stimulation tests to predict the response to AZI. In a placebo-controlled, parallel designed trial we studied 26 patients with esophageal hypomotility defined in the Chicago Classification V3.0 as 1) >50% ineffective swallows with DCI < 450 mmHg-s-cm and/or 2) >50% swallows with fragmented peristalsis. Patients underwent HRM pre and post treatment with AZI 250mg or placebo. Each HRM included MRS (5 water swallows), AC (10 water swallows during abdominal compression) and BS (10 bread swallows). DCI was used to assess strength of baseline contractions and during stimulation tests.

Results: AZI normalised EH in 5/9 patients with abnormal DCI and in 7/13 patients with fragmented peristalsis whilst placebo did not normalized EH. AZI increased DCI from 337.7 ± 286.2 mmHg.cm.s to 617.8 ± 384 mmHg.cm.s (P= 0.01). The % increase of DCI by AZI was 162.9 ± 361.2 and by placebo was 64.5 ± 92.8. DCI ratio (after MRS/baseline) >1.2 segregated responders to AZI with a sensitivity of 78%, specificity 75%, PPV 87.5%, NPV 60% and LR of 3.11. A DCI after MRS of ≥395 mmHg.cm.s segregated responders to AZI with a sensitivity of 80%, specificity 75%, PPV was 80%, NPV 75% and LR 3.2. Combining the criteria for DCI after MRS and DCI during abdominal compression further increased sensitivity and negative predictive value. DCI during bread swallows could not predict response to AZI.

Conclusion: AZI but not placebo improved esophageal contractions in a subgroup of patients with significant esophageal hypomotility. Pre-treatment stimulation tests (MRS and AC) could identify with moderate accuracy those patients more likely to respond to AZI therapy.

Disclosure of Interest: None declared

P0484 ASSESSMENT OF ESOPHAGEAL CONTRACTILE PATTERN AND BOLUS TRANSIT BY USING DIFFERENT BOLUS CONSISTENCIES IN PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE (GERD)

E. Coss-Adame¹, on behalf of Pinzon-Te Lol-Be, Zavala-Solares. R. Monica, Valdovinos-Díaz. Miguel Angel

¹Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico, Mexico

Contact E-mail Address: enriquecossmd@gmail.com

Introduction: Conventional manometry protocol using ten 5 ml liquid swallows has been standardized for the diagnosis of peristaltic abnormalities being the basis for current classification of esophageal motor disorders. Recently, there are reports using multiple rapid swallowing and different bolus consistencies in order to detect more esophageal contractile abnormalities.

Aims & Methods

Aim: To investigate peristaltic contractility patterns and bolus transit (BT) by comparing different bolus consistencies in patients with GERD.

Methods: Patients with GERD were recruited consecutively and grouped as follows: Group 1, Erosive GERD (positive upper endoscopy and pHmetry) and group 2, non-erosive reflux disease (negative upper endoscopy and positive pHmetry). High Resolution Manometry (HRM, MMS, Netherlands with 22 sensors, water-perfused) in supine position was used and multichannel intraluminal impedance-pHmetry (MII-pH) with 6 impedance sensors (3,5,7,9,15,17 cm) and 1 pH sensor (5 cm above lower esophageal sphincter) was used (Given Imaging) to assess BT. Study protocol included: ten 5 ml liquid swallows (LS), three 5 ml applesauce swallows (AS) and three 7.5 grs of sliced-bread (SB), were provided during HRM and at the beginning of MII-pH recording separately. Peristaltic abnormalities were classified as follows: Small breaks (>2 but < 5 cm gap), Large breaks (> 5 cm gap) and failed (< 3 cm wave integrity). A transit time > 8 s was defined as delayed and an incomplete bolus transit if exit from distal impedance sensor was not detected for each of the bolus consistencies. Data is summarized using median and ranges. Statistical analysis compared contractile patterns and BT between groups and after different bolus consistencies using non-parametric test.

Results: 38 patients were recruited, median age 45 (28-63), 18 Erosive (F 67%), and 20 non-erosive (F 75%). Overall, there were no differences in any of the manometric parameters between groups. However, there were significantly more peristaltic abnormalities (large breaks p=0.03 SB; small breaks p=0.01 AS and p=0.008 SB) in non-erosive patients (small breaksp=0.01 SB) and in erosive patients when comparing with LS. In addition, more incomplete BT occurred with AS (p=0.0001) and SB (p=0.007) when compared with LS in non-erosive group. Prolonged transit time was observed in AS (p=0.0001) and SB (p=0.0001) in non-erosive but not in erosive group.

Conclusion: Our data suggest that assessment of esophageal contractility and BT with different bolus consistencies may yield more abnormalities when compared with conventional protocol. Whether these findings are relevant for functional outcomes requires further study.

Disclosure of Interest: None declared

P0485 GASTROINTESTINAL SYMPTOM BURDEN IN A SWEDISH POPULATION BASED COHORT WITH INSULIN DEPENDENT DIABETES MELLITUS

J. Brun¹, H. Törnblom¹, E. Olausson¹, G. Ringström¹, M. Simrén¹

¹Dept of Gastroenterology & Hepatology, Institute of Medicine, Gothenburg, Sweden

Contact E-mail Address: jan.brun@vgregion.se

Introduction: Long-standing diabetes mellitus (DM) is afflicted with a wide variety of complications that may cause symptoms from multiple organ systems including the gastrointestinal (GI) tract. Data from other centers have claimed that as many as 75% of patients attending DM clinics report significant GI symptoms.

Aims & Methods: The aim of our study was to understand the extent to which a defined cohort of Swedish patients with DM suffers from GI symptoms. Patients with insulin dependent DM type 1 (IDDM1) and type 2 (IDDM2) who attended the diabetic outpatient clinics at two county hospitals were included in the study. They were sent the Patient Assessment of upper GastroIntestinal Symptom Severity Index (PAGI-SYM) questionnaire for assessment of GI symptom severity which consists of 20 questions answered by use of a six-point Likert response scale, ranging from 0 (none) to 5 (very severe). The Gastroparesis Cardinal Symptom Index (GCSI) was calculated for nausea/vomiting, postprandial fullness/early satiety and bloating. Hospital anxiety and depression (HAD) scale was used for psychological assessment and the short form (SF) 36 questionnaire summary measures for physical and mental health. For those who answered the questionnaires, clinical information was retrieved from medical records regarding complications related to long-standing DM.

Results: We included 754 patients (mean age 48 years, range18-82 years). The questionnaires were answered by 434 patients (response rate 57.8%), and 363 (83.3%) of these had IDDM1 and 73 (16.7%) had IDDM2. The duration of insulin treatment was 21 ± 13 years. Ratings of individual symptoms are given in table 1. The mean GCSI total score in the cohort was 0.7 ± 0.8. Females with IDDM had significantly higher GCSI total score (0.853 vs. .622; p=0.003), GCSI nausea/vomiting score (0.42 vs. 0.28; p=0.019) and GCSI bloating score (1.2 vs. 0.81; p=0.001) compared to males. There was a strong correlation (p=0.001) between SF-36/HAD and the GCSI total, nausea/vomiting and bloating scores. There was no significant difference in GCSI scores comparing patients with IDDM1 and IDDM2, also not within sexes. Patients with one or more complications related to long-standing DM reported GI symptoms to the same extent as those with no complications and more complications was not associated with higher GCSI scores.

Table 1.

Proportion of patients reporting no (0), mild-moderate (1-3) or severe (4-5) intensity of individual symptoms included in the GCSI score.

PAGI-SYM (n=434)	Non(%)	Mild-moderaten(%)	Severen(%)
Nausea	323 (75)	98 (23)	11 (2)
Retching	358 (83)	69 (16)	6 (1)
Vomiting	398 (92)	32 (7)	4 (1)
Stomach fullness	179 (41)	242 (56)	13 (3)
Unable to finish a normal-sized meal	329 (76)	96 (22)	9 (2)
Feeling excessively full after meals	244 (56)	167 (39)	23 (5)
Loss of appetite	296 (68)	140 (29)	15 (3)
Bloating	234 (54)	175 (40)	24 (6)
Stomach visibly larger	250 (58)	153 (35)	31(7)

Conclusion: Females with IDDM reported more GI symptoms compared with males. Although the total GI symptom burden in our study corresponded to “very mild” there was a highly significant correlation between the GCSI subscores; total, nausea/vomiting, bloating and mental and physical health and anxiety and depression. Furthermore it appears that the number complications to long standing DM do not per se imply an increase in reported GI symptoms.

Disclosure of Interest: None declared

P0486 POSTPRANDIAL PROXIMAL GASTRIC ACID POCKET IN PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE IN CHINA

J. Wu¹, Y. Luo¹, Y. Nian¹, D. Liu¹, C. Feng¹, X. Wang¹, J. Zhang¹

¹The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China

Contact E-mail Address: 644353550@qq.com

Introduction: The postprandial proximal gastric acid pocket (PPGAP) is an unbuffered area which escapes neutralization by food and the pH is lower than 4 of the proximal stomach between nonacid segments distally (food) and proximally (lower esophageal sphincter or distal esophagus). It has been noticed in normal individuals and patients with gastroesophageal reflux disease (GERD). The PPGAP is believed to play an important role in GERD. However, it is still poorly understood.

Aims & Methods

Aims: In this study,we analyze the differences of PPGAP between patients with GERD and normal individuals in China.

Methods: 17 normal individuals and 20 patients with GERD participated in this study. All the subjects underwent a high-resolution manometry in a fasting state to identify the location of the lower border of the lower esophageal sphincter (LBLES).Then a station pull-through pH monitoring was performed from 5 cm below the LBLES to the esophagus in increments of 1 cm in a fasting state and 10 min after a standardized meal. The PPGAP was defined by the presence of acid reading (pH < 4) in a segment of the proximal stomach between non-acid segments distally (food) and proximally (lower esophageal sphincter or distal esophagus). The appearing time,disappearing time, length and pH of PPGAP were recorded.

Results: Our results show that a PPGAP is present in 100% of the patients with GERD and normal individuals. Compared to the normal individuals,the disappearing time of PPGAP in patients with GERD was significantly later (132.65 ± 45.22min vs 74.53 ± 30.64min, p < 0.01), the lasting time of PPGAP was significantly longer (118.50 ± 49.70min vs 55.59 ± 34.25min, p < 0.01), the length of PPGAP was significantly longer (5.00 ± 2.34cm vs 1.88 ± 1.11cm, p < 0.01), the lowest pH of PPGAP was significantly lower (1.01 ± 0.40 vs 1.67 ± 0.49, p < 0.01), and the mean pH of PPGAP was significantly lower (1.29 ± 0.47 vs 2.03 ± 0.43, p < 0.01). While there was no significant difference in the appearing time of PPGAP between the patients with GERD and the normal individuals (14.25 ± 9.72min vs 18.47 ± 10.74min, p=0.218).

Conclusion: The PPGAP is present generally in normal individuals and the patients with GERD. Compared to the normal individuals, in the patients with GERD, the lasting time of PPGAP is longer, the length of PPGAP is longer and the pH of PPGAP is lower. The PPGAP may be the reservoir from which acid reflux events originate. It may plays an important role in GERD. So in the future, the PPGAP may be an attractive target for GERD therapy.

Disclosure of Interest: None declared

P0487 ESOPHAGEAL MOTILITY IN MORBIDLY OBESE PATIENTS WITH TYPE 2 DIABETES

J. Lorentzen¹, A. W. Medhus², J. Hjelmesæth³⁴, D. Hofsø³, T.-I. Karlsen⁵, R. Sandbu³⁶, B. Seip¹

¹Medical Department, Vestfold Hospital Trust, Tønsberg, ²Medical Department, Department of Gastroenterology,Oslo University Hospital, Oslo, ³Morbid Obesity Centre, Vestfold Hospital Trust, Tønsberg, ⁴Faculty of Medicine, University of Oslo, Oslo, ⁵Department of Health and Nursing Sciences, University of Agder, Grimstad, ⁶Department of Gastroenterology, Surgical Clinic, Vestfold Hospital Trust, Tønsberg, Norway

Contact E-mail Address: jolanta.lorentzen@siv.no

Introduction: There is a scarcity of studies of motility disorders in morbidly obese patients with diabetes.

Aims & Methods: We aimed to assess esophageal motility in this group of patients. Patients with BMI ≥ 35 kg/m² and type 2 diabetes eligible for bariatric surgery were included from 01.01.2013 to 30.03.2015. All patients were recruited from a tertiary care obesity centre in Southern Norway. Gastrointestinal Symptom Rating Scale (GSRS) was applied to measure self-reported upper GI symptoms. High-resolution multichannel manometry was used to study esophageal motility.

Results: A total of 51 patients were included, mean age 47 years (range 32-61) and mean BMI 43 (range 35-58) kg/m². Esophageal manometry revealed dysmotility in 17 patients (33%), involving the esophageal body in 10 patients, with an abnormal mean DCI (distal contractile integral) in the range of 5000-8000 mmHg*sec*cm. Lower esophageal sphincter (LES) residual pressure was normal. The remaining 7 patients had ineffective esophageal motility (IEM) defined by at least 30% ineffective contractions out of 10 wet swallows. No patients reported difficulty with swallowing or chest pain according to GSRS.

Conclusion: Esophageal dysmotility was found in 1 out of 3 morbidly obese patients with type 2 diabetes, and the most prevalent finding was abnormal high DCI, consistent with the nutcracker esophagus, which was found in about 1 out of 5 (18%). None of the patients reported relevant symptoms. The present results demonstrate a high prevalence of asymptomatic dysmotility of the esophagus in morbidly obese patients with diabetes mellitus. A study of this patient group before and after bariatric surgery is indicated to elucidate the influence of change in body weight on esophageal dysmotility and related symptoms.

Disclosure of Interest: None declared

P0488 ARE THERE ANY EFFECTS AND CONCOMITANT FACTORS OF GERD WITH OBSTRUCTIVE SLEEP APNEA SYNDROME ?

A. Soylu¹, H. Kaya², S. Çakmak¹, I. Sevindir¹, Y. Okuturlar³, A. Altıntas²

¹Gastroenterology, ²E.N.T Clinic, ³Internal medicine, Bakirkoy Dr Sadi Konuk Research and Training Hospital, Istanbul, Turkey

Contact E-mail Address: aliyesoylu@superonline.com

Introduction: OSAS is one of the sleep disturbances in the society which has a prevalance of 1-5% and has various risk factors. General risk factors related to OSAS: age, gender, obesity, snoring, drugs, genetics, etc. Our objective was to study the OSAS cases which is concomitant with obesity and questioning other contributing factors.

Aims & Methods: We classified 62 patients (Female: 6, Male: 56 ) after GERD questioning into two groups: Patients having Reflux disease and the patients without reflux disease. We also questioned patients BMI scores, waist circumferance, smoking and alcohol consumption, reflux score, BECK anxiety and depressing score, sleep quality ( good, medium, bad ). We recorded Apnea and Hypopnea index and the mean O₂ saturation values of the patients. The Patients are divided into two groups as patients with reflux disease and the without reflux disease. We compared the data of the two groups.

Results: There was no difference between Reflux (+) and Reflux (-) patients mean ages (p=0.424), mean BMI's (p=0.136), mean waist circuference (p=0.343), mean neck circumference (p=0.359), mean Epworth Scale (p=0.107), mean Apnea Hypopnea index (p=0.908), mean Oxygen saturation (p=0.326), alcohol consumption (p=0.620), smoking (p=0.966) .

There was significant difference in sleep quality between two groups (Reflux+, and Reflux -)(p= 0.037). The bad and very bad sleep quality answer is higher in the reflux + group (56%) than reflux – group (27%).

There was no statistically significant correlation between Reflux Score, Epworth Scale, Apnea Hypopnea index and 0₂ saturation (p > 0.05).

There was significantly positive correlation between Reflux Score, BECK Anxiety Scale, and Beck Depression Scale (r=0.382 p=0.002, r=0.254 p=0.046 respectively).

Conclusion: The Apnea and Hypopnea index and Mean O₂ saturation is not affected in patients with reflux disease. Reflux disease worsens the sleep quality. Increased reflux score leads increased BECK anxiety and depression scores. The intensity of reflux is associated with anxiety and depression.

Disclosure of Interest: None declared

P0489 ESOPHAGOGASTRIC JUNCTION CONTRACTILE INTEGRAL VALUES CORRELATE WITH OBJECTIVE EVIDENCE OF GERD AT IMPEDANCE-PH MONITORING AND UPPER ENDOSCOPY

S. Tolone¹, N. de Bortoli², E. Marabotto³, C. de Cassan⁴, S. Roman⁵, M. Furnari³, V. Savarino³, L. Docimo¹, E. Savarino⁴

¹Department of Surgery, Second University of Naples, Naples, ²Department of Internal Medicine, University of Pisa, Pisa, ³Department of Internal Medicine, University of Genoa, Genoa, ⁴Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy, ⁵Digestive Physiology, Lyon I University and Labtau, INSERM 1032, Lyon, France

Introduction: The esophagogastric junction (EGJ) has been shown to play a major role as defensive mechanism against gastro-esophageal reflux. In keeping, a new metric, termed the EGJ-contractile integral (EGJ-CI), which can be assessed by high resolution manometry (HRM), has been validated in distinguishing proton pump inhibitors (PPIs) refractory patients with functional heartburn from those with PPI resistant gastro-esophageal reflux disease (GERD). However, data correlating EGJ-CI values with objective evidence of GERD is lacking.

Aims & Methods: We aimed to correlate the EGJ-CI values with impedance-pH and endoscopic findings in patients with GERD. Consecutive patients with typical GERD symptoms were enrolled. All patients underwent upper endoscopy, HRM and impedance-pH testing off-PPI therapy. EGJ-CI was calculated using the distal contractile integral tool box during three consecutive respiratory cycles. The value was then divided by the duration of these cycles. A value below 13 mmHg*s*cm was considered as a defective EGJ-CI according to medical literature (the 5th percentile measured in 75 healthy volunteers). We assessed esophageal acid exposure time (AET), number of reflux episodes (NRE) and symptom association analysis (SAA) using both symptom association probability (SAP+ if ≥95%) and symptom index (SI+ if ≥50%). A positive impedance-pH monitoring was considered in case of abnormal AET and/or NRE and/or positive SAA. Finally, we analyzed three different cut-off values of EGJ-CI (13 mmHg*s*cm, as the 5th percentile in healthy volunteers, 10 and 5 mmHg*s*cm, arbitrary set) with receiver operating characteristic (ROC) curve in order to provide the optimal balance between diagnostic sensitivity and specificity for impedance-pH detected GERD diagnosis, abnormal number of reflux, pathologic AET and positive symptom association.

Results: Among 130 [65M/65F; median age 53 (21-76)] prospectively enrolled patients, 91 had GERD (abnormal AET and/or elevated NRE and/or positive SAA) and 39 had functional heartburn (FH) (negative endoscopy, normal AET, normal NRE and negative SAA). GERD patients had a lower median value of EGJ-CI [11 (3.1-20.7) vs. 22 (9.9-41), p < 0.02] compared to FH patients. Patients with a defective EGJ-CI (<13 mmHg*s*cm) had more frequently a positive impedance-pH monitoring or esophageal mucosal lesions at upper endoscopy (p < 0.05 and p < 0.05, respectively) than patients with a normal EGJ-CI. As shown in the Table, an EGJ-CI cut-off value of 5 mmHg*s*cm yielded the best performance in identifying GERD at impedance-pH (sensitivity 89%, specificity 63%).

Abstract number: P0489

	EGJ-CI cut-off value 13 (sens%>spec%)	EGJ-CI cut-off value 10 (sens%>spec%)	EGJ-CI cut-off value 5 (sens%>spec%)
Patients with GERD	64% - 46%	74% - 54%	89% - 63%
Patients with abnormal NRE	63% - 24%	72% - 29%	79% - 51%
Patients with abnormal AET	66% - 35%	74% - 42%	87% - 54%
Patients with positive symptom association	58% - 48%	70% - 53%	87% - 61%

Conclusion: A defective EGJ-CI at HRM is associated with objective evidence of GERD at upper endoscopy and/or impedance-pH monitoring. An EGJ-CI cut-off value of 5 mmHg*s*cm yielded the best performance in diagnosing GERD at impedance-pH monitoring.

Disclosure of Interest: S. Tolone: None declared, N. de Bortoli: None declared, E. Marabotto: None declared, C. de Cassan: None declared, S. Roman: None declared, M. Furnari: None declared, V. Savarino: None declared, L. Docimo: None declared, E. Savarino Lecture fee(s): Given Imaging

P0490 CORRELATION BETWEEN ESOPHAGOGASTRIC JUNCTION CONTRACTILE INTEGRAL AND GERD: A STUDY USING HIGH RESOLUTION MANOMETRY AND GERDQ QUESTIONNAIRE

S. Tolone¹, N. de Bortoli², E. Marabotto³, C. de Cassan⁴, S. Roman⁵, M. Furnari³, V. Savarino³, L. Docimo¹, E. Savarino⁴

¹Department of Surgery, Second University of Naples, Naples, ²Department of Internal Medicine, University of Pisa, Pisa, ³Department of Internal Medicine, University of Genoa, Genoa, ⁴Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy, ⁵Digestive Physiology, Lyon I University and Labtau, INSERM 1032, Lyon, France

Introduction: Recently, a new high resolution manometry (HRM) metric, termed the EGJ-contractile integral (EGJ-CI), has been introduced in order to better identify a defective EGJ function and to distinguish proton pump inhibitors (PPIs) refractory patients with functional heartburn from those with PPI resistant gastro-esophageal reflux disease (GERD). To date, data correlating EGJ-CI values with reflux symptoms and HRM features is lacking.

Aims & Methods: We aimed to correlate the EGJ-CI values with symptoms and HRM features in suspected GERD patients. Consecutive patients with typical reflux symptoms were enrolled. Patients were invited to define their symptoms using the validated GerdQ questionnaire¹. A positive GerdQ was considered when equal or >9 (range 0-18). Further, all patients underwent upper endoscopy, HRM and impedance-pH testing off-PPI therapy. EGJ-CI was calculated using the distal contractile integral tool box during three consecutive respiratory cycles. The value was then divided by the duration of these cycles. A value below 13 mmHg*s*cm was considered as a defective EGJ-CI according to medical literature (the 5th percentile measured in 75 healthy volunteers). Three morphological types of EGJ were defined based on the presence of axial cranial separation between lower esophageal sphincter (LES) and crural diaphragm (CD): Type I, no separation; Type II, minimal separation (>1 and <2 cm); Type III, >2 cm of separation. Manometric pattern was defined according to the Chicago Classification v. 3.0.

Results: We prospectively enrolled 130 [65M/65F; median age 53 (21-76)] patients. Sixty-four (49.2%) patients had a defective EGJ-CI (<13 mmHg*s*cm), whereas 66 (50.8%) had a normal value. Mean GerdQ score was greater in patients with a defective EGJ-CI compared to those with a normal EGJ-CI (15 vs. 8, p < 0.02). Moreover, a positive GerdQ (equal or >9) was more common in patients with a defective than normal EGJ-CI (54.9% vs. 35.9%, p < 0.05). At HRM, the study of LES-CD position allowed us to classify as Type I EGJ 60 (46.2%) patients, as Type II EGJ 50 (38.5%) patients and as Type III EGJ 20 (15.4%) patients. Type I EGJ showed the higher median value of EGJ-CI [20 (12.5-36) vs. 10.6 (3.9-17.9), p < 0.001, vs. 2.95 (0.2-8.4), p < 0.001] than Type II and III EGJ. A significant difference was also recorded between these latter two groups (p < 0.008). As to the motility pattern, patients with a defective EGJ-CI showed a lower frequency of normal motility (57.7%) in favor of ineffective esophageal motility (32.3%), whereas outflow obstruction pattern was present only in normative EGJ-CI patients. However, significant differences were not reached among the various groups.

Conclusion: A defective EGJ-CI at HRM is associated with the presence of more frequent and severe reflux symptoms and GERD-related HRM features (i.e. type II or III EGJ and ineffective esophageal motility pattern) compared to a normal EGJ-CI. Thus, our data suggest that a defective EGJ-CI plays a major role in GERD pathogenesis.

Disclosure of Interest: S. Tolone: None declared, N. de Bortoli: None declared, E. Marabotto: None declared, C. de Cassan: None declared, S. Roman: None declared, M. Furnari: None declared, V. Savarino: None declared, L. Docimo: None declared, E. Savarino Lecture fee(s): Given Imaging

P0491 ACID-HYPERSENSITIVE OESOPHAGUS REFRACTORY TO PPI: RELEVANCE OF GAS-RELATED REFLUX EVENTS AND HYPERVIGILANCE

G. Amarasinghe¹, P. Woodland¹, J. L. S. Ooi¹, E. Yazaki¹, Q. Aziz¹, D. Sifrim¹

¹Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom

Contact E-mail Address: p.woodland@qmul.ac.uk

Introduction: Amongst patients who are refractory to PPI therapy who undergo reflux monitoring, there is a subgroup classified as having acid hypersensitive oesophagus. Hypersensitive oesophagus (HO) is defined as typical symptomatic perception of reflux events in the context of physiological levels of gastro-oesophageal reflux.

Within patients with acid hypersensitive oesophagus there are likely to be patients who have predominantly gas-related reflux episodes (supra-gastric belches/gastric belches) and those who have predominantly liquid only reflux episodes. There may also be those who are truly hyper-sensitive, and others who are more hyper-vigilant to reflux events. We anticipated that those patients with gas-related reflux events (particularly supragastric belching related) may be more hyper-vigilant, and that this may manifest as a shorter delay to pushing the symptom marker button after reflux events during 24 hour reflux monitoring.

Aims & Methods: Our aim was to assess the prevalence of gas-related and liquid only reflux events in patients with HO, and to assess time to symptom marker button press for these events.

36 consecutive patients with HO as defined as normal oesophageal acid exposure (<4.2%) with typical symptoms of heartburn or regurgitation and positive symptom-reflux association (SI >50% and/or SAP >95%) were identified. Reflux events related to symptoms were manually examined and the nature of the reflux event was characterised. Time from onset of reflux event to event marker press was measured in seconds.

Each patient was categorised as to the predominant reflux type (suprgastric belch, gastric belch or liquid only).

Relfux parameters were also measured in a comparison group of 50 consecutive patients pathological oesophageal acid exposure.

Results: 417 symptomatic reflux episodes were recorded by the 36 patients. The prevalence of gas related reflux events was 64% and liquid reflux events was 36%. Of the gas-related events, 139/267 (33% of total) were related to supragastric belches and 128/267 were related to gastric belches. Time to perception for liquid, supragastric belch, gastric belch, and liquid-related reflux events were not different.

10 patients (28%) had predominantly supragastric belch related reflux events, 10 had predominantly gastric belch related reflux, and 11 (30%) had predominantly liquid only reflux events. 5 patients had a mixed picture.

In the group of 50 patients with pathological oesophageal acid exposure, only 12% had predominant supragastric belching related reflux.

When time to recording of symptoms was analyzed on a per patient basis, no difference was seen.

Conclusion: In patients with acid hypersensitive oesophagus, the presence of gas associated reflux events related to symptoms accounted for 63% of total reflux events. Contrary to our expectation we could not see a difference in time to perception between liquid, supragastric belch and gastric belch related reflux events. It is possible that there is not a hypervigilant subset in these patients, or that the method used cannot distinguish them.

It was noteworthy that supragastric belching related reflux events accounted for nearly a third of all reflux events in patients with oesophageal hypersensitivity. This may present an opportunity for management of a subset of patients with refractory HO with behavioural therapy to reduce supragastric belching.

Disclosure of Interest: None declared

P0492 THE COMBINATION OF ACID SENSING ION CHANNELS AND 5-HYDROXYTRYPTAMINE RECEPTORS MAY BE INVOLVED IN PAIN SENSING IN GASTRO-ESOPHAGEAL REFLUX DISEASE

A. Shcherbakova¹², H. Abdel-Aziz³⁴, O. Kelber⁴, G. Ulrich-Merzenich¹

¹Medical ClinicIII/UKB, ²Volga-Technical University, Bonn, ³University of Münster, Münster, ⁴Scientific Department, Steigerwald ArzneimittelGmbH, Darmstadt, Germany

Contact E-mail Address: gudrun.ulrich-merzenich@ukb.uni-bonn.de

Introduction: We had earlier demonstrated that STW-5 and omeprazole affect multiple chemokine families on genome and proteome level and involve G-protein coupled receptor and MAP-kinase signaling to reduce inflammation in the esophageal tissue in our rat model for gastro-esophageal reflux disease (GERD)^1,2. Pain is a prominent symptom of GERD and commonly related to acidic reflux. The mechanisms of acid induced activation of esophageal afferent nerves are not well understood. Recently it was shown that serotonin, which is the ligand for 5-hydroxytryptamine receptors, can also activate acid sensing ion channels³.

Aims & Methods: We analysed in our subchronic refluxesophagitis (RE) rat model the transcript modulation of acid sensing ion channels and of 5-hydroxytryptamine (5-HTR) subtypes in the esophageal tissue.

Methods: Rats were pretreated with either STW 5 (0.5 or 2ml/kg) a multicomponent herbal preparation, or the PPI omeprazole (O) (30mg/kg) for 7 days. Esophagitis was induced surgically followed by a further 10d treatment. On day 10 animals were sacrificed. RNA was isolated from defined tissue areas of the esophagi for Agilent whole genome microarray (rat). Data were analysed by Ingenuity.

Results: Tissues of animals suffering from RE showed a small, but significant increase in the expression of the ASIC-subtype 4 (3.8f, p < 0.001) and of 5-HTR2A (3fold), 5-HTR2B (6.6f), and 5-HTR7 (9.3f) (<0.001) compared to sham. Thus, both – ASICs and distinct 5-HTR subtypes- were up-regulated during the inflammatory process in our rat model. The higher expression of ASIC4 was not found in tissues of animals treated with either STW-5 (2ml/kg) or with O (30mg/kg). Minor differences, especially in the magnitude of down regulation, were seen for the 5-HTR subtypes after treatment with STW 5 and O. Interestingly serotonin is not only the ligand for 5-HTR subtypes, but also an inflammatory mediator which can activate ASICs in peripheral nerve tissue to activate a central pain response².

Conclusion: Acid-sensing ion channels and 5-hydroxytryptamine receptors may form a communication network involved in pain sensing and signaling in gastro-esophageal reflux disease. The down-regulation of ASIC4 and 5-HTR-subtypes in the esophageal mucosa may be responsible for the fast pain relief in responders to PPIs and to STW-5.

Disclosure of Interest: A. Shcherbakova Financial support for research: DAAD-Scholar, H. Abdel-Aziz Financial support for research: Received financial support for research from Steigerwald Arzneimittelwerke GmbH, Conflict with: joined Steigerwald Arzneimittelwerke GmbH as employee, O. Kelber Conflict with: employee of Steigerwald Arzneimittelwerke GmbH, G. Ulrich-Merzenich Financial support for research: Received financial support for research from Steigerwald Arzneimittelwerke GmbH

P0493 POSTURAL CHANGES INDUCE TRANSIENT LOWER ESOPHAGEAL SPHINCTER RELAXATIONS

J. Pérez De La Serna¹, A. Ruiz de León¹, P. Delgado Guillena¹, P. Mateos Sánchez¹, I. Pérez Enciso¹, C. Sevilla Mantilla¹, E. Rey Diaz-Rubio¹

¹Gastroenterology, Hospital Clínico San Carlos, Madrid, Spain

Contact E-mail Address: jperezsernab@gmail.com

Introduction: Transient lower esophageal sphincter (LES) relaxations (TLESR) constitute the major mechanism of physiological gastroesophageal reflux (GER). They are also responsible for 65% of reflux episodes in patients with mild esophagitis and they facilitate belching. They appear mainly after meals and are produced by a reflex mechanism triggered by distension of gastric fundus. They are easily detected by high-resolution manometry.

Aims & Methods: The aim of the study was to determine whether postural changes, without the effect of meals, facilitate the occurrence of TLESR.

Records of 143 patients (77 M, 66 M) (mean age 53 SD 15.8, range:18 to 90 years) referred to our Motility unit for assessment of dysphagia or GERD were retrospectively analyzed. All patients underwent high-resolution manometry (ManoScan, Sierra Scientifics). After fasting for at least 8 hours studies were conducted randomly in supine, right side, left side and seated position. The TLESR were identified as a decrease in LES resting pressure to the level of gastric pressure, inhibition of diaphragmatic crura and unrelated to swallowing.

Results: TLESR were recorded in 68 patients (47.55%) (35 M, mean age 55 SD 15 y. and 33 F, mean age 54 SD 15.8 y.). In 12 cases (8 M) esophageal shortening was appreciated. In the remaining 63 patients (40 F, 23 M) no modifications of the esophagogastric junction were observed except for variations in LES resting pressure referred to the gastric pressure. A total of 94 TLESR: 40 in the sitting position, 34 in the right lateral decubitus, 15 in the left lateral decubitus and 5 in the supine position were recorded. Most of TLESR occurred in the change from supine to a seated position or from supine or right lateral to left lateral decubitus.

Conclusion: TLESR are often triggered by postural changes, regardless of meals and may be associated with GER when the patient change their body position like going to bed, getting up or during movements lying down.

Disclosure of Interest: None declared

P0494 NUTRITIONAL PATTERN OF RUSSIAN GASTROESOPHAGEAL REFLUX DISEASE PATIENTS

M. Konovalova¹, S. Morozov¹, V. Isakov¹

¹Dpt. Gastroenterology and hepatology, Institute of nutrition, Moscow, Russian Federation

Contact E-mail Address: sunnysister@mail.ru

Introduction: There is a lot of controversies about probable influence of dietary patterns on the disease progression and success of treatment in GERD. Nutritional pattern of GERD patients in Russia have not been studied yet.

Aims & Methods: The aim of the study was to assess the nutritional pattern of GERD patients in Russia compared to healthy controls.

Methods: One hundred twenty-four GERD patients (54 men, 70 women, age (M ± m) 46 ± 17.7 yrs; BMI (M ± m) 28.5 ± 0.6 kg/m²) and 41 controls (8 men, 33 women, age (M ± m) 42 ± 12.4yrs; BMI (M ± m) 28.3 ± 1.3 kg/m²) were examined using validated [1] food frequency questionnaire. Diagnosis of GERD was confirmed by typical symptoms and validated GerdQ questionnaire. Non-parametric statistics (Statistica 10, StatSoft Inc, USA) was used to investigate the difference between dietary patterns in GERD patients and controls.

Results: The studied and the control group did not differ on BMI, age and sex distribution (p > 0.05).

Main studied parameters of dietary patterns are shown in the table 1. It was found that average total fat and protein intake was higher in GERD group compared to controls. In contrast, average total fiber intake was significantly higher in controls, but both groups consumed less fibers, then it generally recommended (20 g or more/day). There was no difference between two groups on the carbohydrates, starch and mono/disaccharides intake.

Abstract number: P0494 Table 1.

Dietary pattern of GERD patients in Russia.

	Protein, g/dayM ± m	Total fat, g/dayM ± m	Total carbohydrates, g/dayM ± m	Dietary fiber, g/day,M ± m	Mono/disaccharides, g/dayM ± m	Starchg/dayM ± m
GERD (n=124)	97.5 ± 4.0*	135.2 ± 5.6†	249.8 ± 9.5	7.19 ± 0.4‡	124.6 ± 5.7	113.8 ± 8.5
Controls (n=41)	77.7 ± 4.0*	103.3 ± 5.1†	223.7 ± 14.1	11.4 ± 0.8‡	126.2 ± 9.6	97.7 ± 8.2

Note: *, †,‡ - p < 0.05

Conclusion: Nutritional pattern of Russian GERD patients are characterized by higher fat and protein intake compared to controls and insufficient consumption of dietary fiber that may influence pathogenesis of the disease.

Disclosure of Interest: None declared

P0495 LARYNGOPHARYNGEAL REFLUX AND COUGH REFLEX SENSITIVITY

M. Duricek¹, P. Banovcin¹, T. Halickova², T. Zatko³, R. Hyrdel¹, M. Kollarik³

¹Department of Gastroenterology, Jessenius Faculty of Medicine, Comenius University, Martin, ²Department of otorhinolaryngology, Central Military Hospital Ruzomberok, Ruzomberok, ³Deparment of pathophysiology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia

Contact E-mail Address: pbanovcin@gmail.com

Introduction: Cough reflex sensitivity to inhaled irritants is thought to be related to the functional state of cough-triggering afferent nerve terminals in the larynx and large airways. Laryngopharyngeal reflux (LPR) causes larynx and potentially large airways irritation. However, the relationship between the cough reflex sensitivity and the LPR is not completely understood.

Aims & Methods: We hypothesized that the cough reflex sensitivity is positively correlated with the LPR. Our hypothesis predicts that patients with more frequent LPR will have lower cough reflex threshold. Consecutive patients referred by ENT physician for suspected LPR were evaluated. Laryngopharyngeal reflux was quantified by 24h pH-impedance monitoring using Given Imaging system. Proximal pH sensor was placed1 cm above upper esophageal sphincter as detected by high resolution manometry.

Cough reflex sensitivity was determined by single breath capsaicin inhalation challenge of doubling concentrations of capsaicin (0.49-500μmol/l) using KoKo PFT system. Cough threshold C2 was defined as the lowest concentration of capsaicin that evoked 2 or more coughs.

For statistical analysis C2 values were –log transformed and Pearson coefficients were calculated for correlation with reflux parameters.

Results: 13 consecutive patients with suspected LPR were evaluated. LPR episodes were detected by impedance monitoring in all patients. The number (median[interquartile range]) of LPR episodes was 15[19-29]. Cough sensitivity expressed as C2 concentration of capsaicin (geometric mean[95%CI]) was 13.4[6.6-27.1]μmol/l.There was a strong positive correlation between the cough sensitivity and the number of LPR episodes (R=0.77, P < 0.01). In contrast there was no correlation between the total number of gastroesophageal reflux episodes in the esophagus (R=0.47, P > 0.1). Total number of reflux episodes was detected by distal pH sensor placed 5 cm above manometrically determined lower esophageal sphincter. 5 of 13 patients had positive pH monitoring test based on DeMeester score >14.72 indicating pathological distal esophageal acid exposure. The number of LPR episodes and cough sensitivity in these patients were virtually identical to those with negative pH monitoring test.

Conclusion: The number of laryngopharyngeal reflux episodes positively correlates with cough reflex sensitivity in patients with laryngopharyngeal reflux. These results may suggest a direct relationship between the intensity of laryngeal irritation and cough.

Supported byBioMed Martin(ITMS: 26220220187) and Research grant of Ministry of Health Slovak Republic (2013/33-UKMA-10)

Disclosure of Interest: None declared

P0496 ESOPHAGOGASTRIC JUNCTION MORPHOLOGY ASSESSMENT BY HIGH RESOLUTION MANOMETRY AND ITS RELATIONSHIP WITH GASTROESOPHAGEAL REFLUX DISEASE IN OBESE PATIENTS CANDIDATE TO BARIATRIC SURGERY

S. Tolone¹, E. Savarino², N. de Bortoli³, M. Frazzoni⁴, M. Furnari⁵, E. Marabotto⁵, C. De Cassan², V. Savarino⁵, L. Docimo¹

¹Second University of Naples, Naples, ²University of Padua, Padua, ³University of Pisa, Pisa, ⁴Baggiovara Hospital, Modena, ⁵University of Genoa, Genoa, Italy

Contact E-mail Address: salvatore.tolone@unina2.it

Introduction: Obesity is a strong independent risk factor of gastroesophageal reflux disease (GERD), esophageal erosions and hiatal hernia (HH) development. Pure restrictive bariatric surgery should not be indicated in case of HH and GERD. In fact, if in most cases bariatric surgery can diminish reflux by losing a large amount of fat, on the other hand some restrictive procedure can worsen or cause the presence of GERD. Also, it is still unclear what is the real incidence of disruption of esophagogastric junction (EGJ) in patients candidate to bariatric surgery. Actually, high-resolution manometry (HRM) can provide accurate information about EGJ morphology, whereas impedance-pH monitoring (MII-pH) can highlight the presence of acid, weakly acid and weakly alkaline reflux and correlate it to symptoms.

Aims & Methods: Aim of this study was to describe the EGJ morphology determined by HRM in obese patients candidate to bariatric surgery and to verify if different EGJ morphologies are associated to GERD-related symptoms presence and to different GERD patterns determined by means of MII-pH. All patients underwent a standardized questionnaire for symptom presence and severity (GERDQ), upper endoscopy, HRM and MII-pH. EGJ was classified as: Type I, no separation between the lower esophageal sphincter (LES) and crural diaphragm; Type II, minimal separation (>1 and <2 cm); Type III, >2 cm separation. At MII-pH, total acid exposure time (AET, %) and total number of refluxes (TNR) were assessed. A healthy-volunteers group (HVs) was used as control.

Results: One hundred thirty-eight obese (BMI > 35) subjects and 15 HV (normal weight) were studied. Ninety-eight obese patients referred at least one GERD-related symptom, whereas 40 subjects were symptom-free. According to HRM features, EGJ Type I morphology was documented in 51 (36.9%) patients, Type II in 48 (34.8%) and Type III in 39 (28.3%). EGJ Type III subjects reported more frequently symptoms than EGJ Type I (38/39, 97.4%, vs. 21/59, 41.1% p < 0.001). Obese patients with EGJ Type I showed comparable mean LES pressure and peristaltic function than HV (30.5 ± 8.5 vs. 34 ± 5.2 mmHg, and 80 ±10 vs. 90 ±10 intact peristaltic waves with normal vigor, respectively). EGJ Type II and III patients showed a statistical significant reduction in LES pressure and peristaltic function (22.3 ± 12.2 vs. 34 ± 5.2 mmHg, p < 0.05 and 60 ±10 vs. 90 ±10 intact peristaltic waves with normal vigor, p < 0.05 respectively for Type II and 11.1 ± 5.3 mmHg, p < 0.001 and 40 ±20 normal waves, p < 0.001 for Type III, respectively). At MII-pH, EGJ Type I patients showed similar reflux patterns to HVs (AET 3.4 vs. 2.3%, and TNR 27 ± 5 vs. 21 ± 6); EGJ Type II (AET 5.2, p < 0.05, and TNR 57 ± 21, p < 0.05) and III (AET 7.4, p < 0.001, and TNR 76 ± 33, p < 0.001) showed a significant increase in esophageal acid exposure and in TNR than HVs.

Conclusion: Obese subjects have a high risk of disruption of EGJ morphology. In particular, patients with HH often refer pre-operative presence of GERD symptoms. Thus, testing obese patients with HRM and MII-pH before undergoing bariatric surgery, especially for restrictive procedures, can be useful for assessing presence of HH and GERD.

Disclosure of Interest: None declared

P0497 EFFECTS OF OMEGA-LOOP GASTRIC BYPASS ON ESOPHAGOGASTRIC JUNCTION FUNCTION AND REFLUX

S. Tolone¹, K. Rodriguez², L. Docimo¹, E. Savarino²

¹Department of Surgery, Division of General and Bariatric Surgery, Second University of Naples, Naples, ²Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy

Introduction: Several bariatric operations for morbid obesity have been developed in order to reduce excess body weight. In particular, omega-loop gastric bypass (OGB), consisting primarily of a long linear lesser-curvature gastric tube with a termino-lateral gastro-enterostomy 180–200 cm distal to the ligament of Treitz, was recently introduced with good results in terms of weight loss and improvement of obesity-related co-morbidities. However, concerns have been raised about the potential development of symptomatic biliary reflux gastritis/esophagitis and risk of gastric/esophageal cancer due to chronic biliary reflux. At present, no objective data are available on the effect of OGB on esophago-gastric junction (EGJ) function, reflux occurrence and symptoms.

Aims & Methods: We aimed to evaluate the possible effects of OGB on esophageal motor function and a possible increase in gastro-esophageal reflux. Consecutive obese patients underwent clinical assessment for reflux and dyspeptic symptoms by means of a validated questionnaire, and endoscopy plus high-resolution impedance manometry (HRiM) and 24-h impedance-pH monitoring off-therapy before and 1 year after OGB. During HRiM and impedance-pH tracings analysis we measured: intragastric pressure (IGP), gastroesophageal pressure gradient (GEPG), EGJ morphology, motility pattern according to Chicago classification, distal esophageal acid exposure, number of impedance-detected refluxes and symptom association probability. A group of obese patients who underwent sleeve gastrectomy (SG) was included as the control population.

Results: Fifteen OGB patients [5 males/10 females; mean age 38 ± 8.2 years; mean BMI 46.4 (38-60) kg/m²] were included in the study. After surgery [mean BMI 31 kg/m² (28-42)], none of the patients reported “de novo” heartburn or regurgitation. At endoscopic follow-up 1 year after surgery, esophagitis was absent in all patients and no biliary gastritis nor presence of bile were recorded. Manometric features and patterns did not vary significantly after surgery, whereas IGPs and GEPGs statistically diminished (from a median of 15 to 9.5, p < 0.01 and from 10.3 to 6.4, p < 0.01, respectively) after OGB. In contrast, SG induced a significant elevation in both parameters (from a median of 14.8 to 18.8, p < 0.01 and from 10.1 to 13.1, p < 0.01, respectively). A dramatic decrease in the number of reflux events (from a median of 41 to 7; p < 0.01) was observed after OGB, whereas in patients who underwent SG a significant increase in esophageal acid exposure and number of reflux episodes (from a median of 33 to 53; p < 0.01) were noted.

Conclusion: In contrast to SG, OGB did not compromise the gastro-esophageal junction function and did not increase gastro-esophageal reflux, which explained by the lack of increased IGP and in GEPG as assessed by HRiM.

Disclosure of Interest: S. Tolone: None declared, K. Rodriguez: None declared, L. Docimo: None declared, E. Savarino Lecture fee(s): Given Imaging

P0498 REFLUX TYPE AND NUMBER ARE RELATED TO NUTRITIONAL PATTERNS IN GERD PATIENTS

S. Morozov¹, M. Konovalova¹, V. Isakov¹

¹Gastroenterology&Hepatology, Research Institute of Nutrition, Moscow, Russian Federation

Contact E-mail Address: morosoffsv@mail.ru

Introduction: Little is known about the influence of nutrition on number and reflux type in GERD, therefore dietary recommendations for patients are mostly empirical.

Aims & Methods: The aim of the study was to assess the relationship between GERD patients’ nutrition pattern,presence of the disease and esophageal pH-impedance parameters.

Methods: One hundred twenty four GERD patients (54 men, 70 women, age (M ± m) 46 ± 17.7 yrs; BMI (M ± m) 28.5 ± 0.6 kg/m²) and 41 controls (8 men, 33 women, age (M ± m) 42 ± 12.4yrs; BMI (M ± m) 28.3 ± 1.3 kg/m²) were examined using validated food frequency questionnaire. Number and types of gastro-esophageal refluxes evaluated by 24-hours esophageal pH-impedance recordings (Ohmega, MMS, the Netherlands; 2pH-6 impedance channels catheters, UnisensorAG, USA). Correlation analysis was performed between the number of reflux episodes, their acidity, duration and frequency and quantity of protein, carbohydrates, total fat, fiber and energy intake using non-parametric statistics (Statistica 10, StatSoftInc, USA).

Results: Direct, medium strength correlation was found between presence of GERD and total energy (R=0.23, p < 0.05) and daily fat (R=0.21, p < 0.05) intake. Inverse medium strength correlation was found between dietary fiber intake and presence of GERD (R=-0.26, p < 0.05). Proportion of time with pH < 4 at 5 cm over EGJ significantly correlated with total daily energy and total daily fat intake.Correlation coefficients (Spearmen rank R) between nutritional patterns and esophageal function testing parameters are shown in the table 1.

Abstract number: P0498 Table 1.

Correlation coefficients (Spearmen rank R) between nutritional patterns and esophageal function testing parameters.

	Number of refluxes/day, n	Number of acid refluxes/day, n	Number of weak acid refluxes, n	%time pH < 4 distal 1/3 of esophagus
Total energy, kKal/day	0.35*	0.35*	0.22*	0.19*
Protein, g/day	0.3*	0.25*	0.22*	0.13
Totalfat, g/day	0.33*	0.32*	0.21*	0.19*
Total carbohydrates, g/day	0.18*	0.24*	0.07	0.13
Dietary fiber, g/day	-0.22*	-0.14	-0.24*	-0.1

* - p < 0.05

Conclusion: The obtained data may reflect influence of nutritional patterns on pathogenesis of GERD and should be taken into the account when dietary advice is given to the patient.

Disclosure of Interest: None declared

P0499 THE PHENOMENON OF LEPTIN RESISTANCE IN PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE AND DIFFERENT TYPES OF OBESITY

T. Krolevets¹, I. Lapteva², M. Livzan³

¹Post-Graduate of Department of Therapy with the Course of Occupational (Professional) Diseases, ²Assistant of Department of Therapy with the Course of Occupational (Professional) Diseases, ³Department of Therapy with the Course of Occupational (Professional) Diseases, Russian Federation, Omsk, State Educational Institution of Higher Vocational Education “Omsk State Medical University”, Omsk, Russian Federation

Contact E-mail Address: mts-8-90@mail.ru

Introduction: Gastroesophageal reflux disease (GERD) is one of the most prevalent diseases in the world. Overweight and obesity are recognized as independent risk factors for the emergence and progression of GERD. It is known that visceral fat produced by the biological-active substance (adipokines) to influence the feeding behavior. Leptin is one of the most important adipokines, which acts on the hunger and satiety centers in the hypothalamus, involves in the regulation of energy homeostasis and body weight control. It is known that leptin plays a role in the formation of erosive GERD forms, Barrett's esophagus, which may be associated with its pro-inflammatory activity, proliferative power to induction of epidermal growth factor, as well as antiapoptotic effect.

Aims & Methods: We had an aim to determine the characteristics of the course of GERD based on the study of clinical and endoscopic manifestations of the disease, results of pH monitoring and the phenomenon of leptinresistance in patients with different types of obesity. We performed open comparative cross-sectional studies. We examined 105 patients with GERD and obesity or overweight. We asked patients, assessed an anthropometric indices, did a biochemical analysis of blood, endoscope examination of the esophagus and stomach, pH monitoring, assessed levels leptin and its soluble receptor. We separated patients in two groups: the main group (n = 85) - patients with abdominal type of obesity, the comparison group (n = 20) - with normal volume of waist.

Results: Weight, height, body mass index, level of glucose was higher in main group (p < 0.00003, p < 0.03, p < 0.(10)82, p < 0.02, respectively). Leptin levels in patients with abdominal type of obesity was significantly higher and the level of its receptors was significantly lower (mediana of leptin levels 36,93 (14,69-47,60) in main group versus 9,59 (7,66-19,48), mediana of leptin’s receptors 18,25 (14,69-24,26) versus 23,78 (18,83-32,67), respectively). Between these indicators in main group was revealed negative correlation of mild strength (rs=(-0.424), p < 0.002). There were more patients with Nonalcoholic Fatty Liver Disease in main group (p < 0.001). According to the results of gastrointestinal endoscopy non-erosive GERD form was diagnosed in 92 (87.6%) patients and erosive form was revealed in 13 (12.4%). According to the results of endoscopy in patients with GERD comparison groups differences have not been identified. In group with abdominal type of obesity pH cardia and body of stomach was higher (p < 0.04, p < 0.02, respectively), but time of refluxate’s contact with low pH (pH <4) in these departments was longer in the comparison group (p < 0.05). Positive relationship was found between leptin’s receptors and contact’s time in the range of pH from 3 till 6 in the stomach (rs = (0.645), p <0.03), in the range from 4 till 7 and less than 4 in the esophagus (rs = (0.645), p <0.03, rs = (0.600), p <0.05, respectively), the longest gastroesophageal (rs = (0.624), p <0.03) and alkaline refluxes (rs = (0.640), p <0.03).

Conclusion: The formation of leptinresistance in individuals with overweight and obesity based on the type of fat distribution is associated with course of the GERD.

Disclosure of Interest: None declared

P0500 ASSOCIATION BETWEEN THE FORM OF GASTROESOPHAGEAL REFLUX DISEASE, CARACTERISTICS OF ESOPHAGEAL PH-IMPEDANCE MONITORING AND CYTOKINES EXPRESSION

Y. Evsyutina¹, A. Trukhmanov¹, O. Storonova¹, V. Ivashkin¹, S. Lyamina², I. Malyshev²

¹Sechenov First Moscow State Medical University, ²Moscow State University of Medicine and Dentistry, Moscow, Russian Federation

Introduction: The gastroesophageal reflux disease (GERD) is one of the most common diseases, which affects about 15-25% of the world population. In GERD damage of the esophageal mucosa may occur as a result of different types of refluxate, i.e. gastric, biliary or duodenogastric/mixed. In patients with GERD, depending on the form of the disease, increased expression of pro-inflammatory or anti-inflammatory cytokines.

Aims & Methods: To determine correlations between the form of gastroesophageal reflux disease, parameters of esophageal pH-impedance monitoring and cytokines expression.

This prospective cohort study included 55 patients: 20 with non-erosive reflux disease (NERD) – 55% men; average age 37.7 ± 12.0, 20 with erosive esophagitis (EE) – 65% men; average age 38.3 ± 12.5, and 5 with Barrett’s esophagus (BE) – 100% men; average age 34.2 ± 9.8, and 10 healthy volunteers. We performed on all patients an upper endoscopy, a 24-h esophageal pH-impedance monitoring and the determination of plasma cytokines (IL-4, IL-8, IL-10, IFN-γ, TNF-α) by flow cytometry. The statistical analyses were done using R Statistical Software.

Results: In patients with EE in comparison to patients with NERD and BE we registered a higher total number of acid reflux (p < 0.0001) and a higher esophageal acid exposure (p < 0.0001). Patients with BE, in comparison to patients with NERD and EE, had a higher total number of weakly acid reflux (p=0.01) and higher esophageal weakly acid exposure (p=0.004).

We found the correlations between the level of IL-8 and the total number of acid reflux (Kendall τ=0.76) and with esophageal acid exposure (τ=0.42). The level of TNF-α also correlated with total number of acid reflux (τ=0.69) and with esophageal acid exposure (τ=0.48). The level of IL-4 correlated with the total number of weakly acid reflux (τ=0.48) and with esophageal weakly acid exposure (τ=0.50) as well as the level of IL-10 (τ=0.50 and τ=0.51, respectively).

Conclusion: The levels of TNF-α and IL-8 correlated with total number of acid reflux and with esophageal acid exposure in patients with erosive esophagitis. The levels of IL-4 and IL-10 correlated with total number of weakly alkaline reflux and with esophageal weakly alkaline exposure in patients with Barrett’s esophagus.

Disclosure of Interest: None declared

P0501 THE EFFICACY OF TRANSORAL INCISIONLESS FUNDOPLICATION (TIF) IN CONTROLLING CHRONIC GERD: RESULTS OF A DOUBLE BLIND, SHAM CONTROLLED STUDY

B. Håkansson¹, M. Montgomery¹, J. Tack², G. B. Cadiere³, A. Rajan³, S. Bruley des Varannes⁴, M. Le Rhun⁴, R. Bisschops², A. Thorell¹, U. Arnelo⁵, L. Lundell⁵

¹Karolinska University Ersta Hospital, Stockholm, Sweden, ²Department of Gastroenterology, Catholic University Hospitals Leuven, Leuven, ³Department of Gastroenterology, Park Leopold Clinic, CHIREC, Brussels, Belgium, ⁴CHU Hotel Dieu Institut des Maladies de l’ Appareil Digestif, Nantes, France, ⁵Department of Surgery, Center for Digestive Diseases, Karolinska University Huddinge Hospital, Stockholm, Sweden

Contact E-mail Address: lars.lundell@karolinska.se

Introduction: Until recently only two therapeutic options have been available to control symptoms and to heal the esophagitis in chronic gastroesophageal reflux disease (GERD) patients, i.e. life-long proton-pump inhibitor (PPI) therapy or antireflux surgery. Lately, Transoral Incisionless Fundoplication (TIF) has been developed and found to have a potential to offer a therapeutic alternative for these patients. As part of a comprehensive and stepwise evaluation strategy for the clinical use of TIF, we performed a double-blind, multi-center, sham-controlled study in GERD patients who were chronic PPI users.

Aims & Methods: Patients 18-80 years old, on daily PPIs for > 6 months, with persistent GERD symptoms without PPI therapy (during the titration phase of the study), were included in the trial if they had evidence of two or more of the following while off PPI therapy (>10 days): esophagitis (Los Angeles grade A, B or C), abnormal ambulatory pH study, or moderate to severe GERD symptoms. For enrolment we also required normal or near normal esophageal motility (by manometry or impedance), patients’ willingness to cooperate with post-operative dietary recommendations and assessment tests and signed informed consent. After randomization, those allocated to TIF had the procedure completed during general anesthesia by the TIF2.0 EsophyX system with SerosaFuse fasteners (EndoGastric Solutions, Inc., Redmond, WA, USA). Sham procedure consisted of upper GI endoscopy under general anesthesia. Neither the patient nor the assessor was aware of the treatment group affiliation. The primary effectiveness endpoint was the proportion of patients in clinical remission after 6 months (without being classified as treatment failure). Secondary effectiveness parameters were: PPI consumption, esophageal acid exposure, reduction in GERD symptom scores as assessed by the Quality of Life in Reflux and Dyspepsia and Gastrointestinal Symptoms Rating Scale instruments and healing of reflux esophagitis.

Results: Out of 121 patients screened we finally randomized 44 patients with 22 patients confined to each group. The study groups were well balanced regarding demographic and disease-specific characteristics. The time in remission, during the first six months, is detailed in the table demonstrating a significant superiority offered by the TIF procedure. Likewise, the secondary outcome measures were all in favor of the TIF procedure. As an example, acid reflux time improved from 8.89 (Standard Error of Mean, SEM=0.84) to 3.73 (SEM=0.84) by the TIF intervention (p=0.0002) whereas the sham procedure did not change the acid reflux profile at all.

Group	In Remission (n=22)	Treatment Failure (n=22)
Transoral Incisionless Fundoplication, n (%)	14 (64)	8 (36)
Sham, n (%)	2 (9)	20 (91)
P (Fisher’s Exact test)		=0.0004

Conclusion: Transoral Incisionless Fundoplication (TIF) was found to offer chronic GERD patients, being on long-term treatment with PPI, an effective therapeutic alternative.

Disclosure of Interest: None declared

P0502 PATIENTS WITH NON-ACID REFLUX DISEASE AND THOSE WITH EROSIVE AND NON-EROSIVE REFLUX DISEASE HAVE SIMILAR RESPONSE TO ANTI-REFLUX SURGICAL THERAPY

E. Savarino¹, E. Marabotto², R. Salvador¹, C. de Cassan¹, M. Furnari², P. Zentilin², N. de Bortoli³, S. Marchi³, G. Camerini⁴, V. Savarino⁵

¹Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, ²Department of Internal Medicine, Division of Gastroenterology, University of Genoa, Genoa, ³Department of Internal Medicine, University of Pisa, Pisa, ⁴Department of Surgery, ⁵Department of Internal Medicine, University of Genoa, Genoa, Italy

Introduction: Combined impedance-pH monitoring is considered the gold standard for the detection of reflux episodes. Indeed, several studies demonstrated the increased diagnostic yield of this technique in gastro-esophageal reflux disease (GERD) thanks to its ability to correlate symptoms with both acid and/or non-acid reflux episodes. However, limited data are available about the clinical usefulness of impedance-pH testing in GERD management.

Aims & Methods: We aimed to assess whether refractory GERD patients classified by means of endoscopy and impedance-pH as affected by non-acid reflux disease (NARD), erosive and non-erosive reflux disease (ERD and NERD) may benefit from anti-reflux surgery. Consecutive patients with persisting heartburn and/or regurgitation despite 8 weeks of proton pump inhibitors therapy, were prospectively enrolled in this open label trial. All patients underwent upper endoscopy and 24-hour impedance-pH testing off-therapy. We measured distal esophageal acid exposure time (AET), characteristics of reflux episodes (acid/non-acid) and symptom-reflux association. Then, patients with ERD (endoscopy+), NERD (endoscopy-, AET > 4.2% and/or SAP/SI+ for acid reflux) and NARD (endoscopy-, AET < 4.2% and SAP/SI+ for non-acid reflux or both kind of reflux) underwent laparoscopic Nissen fundoplication (LNF). Before LNF and at 1, 6 and 12 months after surgery, reflux symptoms and quality of life were assessed by using validated questionnaires. Upper endoscopy and impedance–pH monitoring was repeated 1 year after surgery. Surgical treatment failure was considered in case of: persisting typical reflux symptoms and/or objective evidence of GERD (esophagitis at upper endoscopy, abnormal AET and/or number of refluxes, positive symptom association) and/or poor quality of life.

Results: Out of sixty-five refractory patients, forty-eight (24F/24M; mean age 49; 14 ERD, 22 NERD and 12 NARD) were included. At 1 year follow-up after surgery, LNF had similar pathophysiological effects in all groups. Indeed, percentage of patients with abnormal AET (ERD 93% vs 7%, NERD 71% vs 0%) and/or increased number of reflux episodes (ERD 93% vs 0%, NERD 86% vs 0%, NARD 83% vs. 0%), mean AET (ERD 12.9% vs 1.8%, NERD 6.1% vs 0.7, NARD 0.7% vs 0.4%) and median number of total (ERD 100 vs 6, NERD 73 vs 9, NARD 72 vs 10), acid and non-acid refluxes significantly decreased (in all cases, p < 0.01). As to the surgical outcome, the percentage of patients with resolved or markedly improved typical symptoms at 12 months after surgery was similar among the study groups (ERD 93% vs. NERD 82% vs NARD 83%, p=ns). Quality of life similarly improved in all groups (p=ns). Finally, the percentage of failure and/or adverse events did not differ among the groups (ERD 21% vs. NERD 23% vs NARD 17%, p=ns).

Conclusion: Our data show that LNF was a safe and effective procedure in relieving typical reflux symptoms in PPI-refractory patients identified as affected by ERD, NERD and NARD, by means of endoscopy and impedance-pH monitoring. Therefore, impedance-pH testing allowed a more clear identification of refractory patients whose symptoms are related to reflux, thus improving their management and outcome.

Disclosure of Interest: E. Savarino Lecture fee(s): Given Imaging, E. Marabotto: None declared, R. Salvador: None declared, C. de Cassan: None declared, M. Furnari: None declared, P. Zentilin: None declared, N. de Bortoli: None declared, S. Marchi: None declared, G. Camerini: None declared, V. Savarino: None declared

P0503 INFLUENCE OF THORACIC AND ABDOMINAL BREATHING ON THE BASAL PRESSURE OF THE LOWER ESOPHAGEAL SPHINCTER

F. Durchschein¹, C. Högenauer¹, K. M. Hoffmann², A. Eherer¹

¹Division of Gastroenterology and Hepatology, Department of Internal Medicine, ²Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria

Contact E-mail Address: franziska.durchschein@medunigraz.at

Introduction: The lower esophageal sphincter and the adjacent crura of the diaphragm form a functional unit preventing gastroesophageal reflux. Esophageal manometry describes the function of this esophagogastric junction. Active abdominal breathing activates the diaphragmatic crura thus contributing to esophagogastric junction pressure (pEGJ). We performed a controlled prospective study to determine the influence of abdominal versus thoracic breathing on pEGJ using esophageal manometry.

Aims & Methods: After routine High-Resolution esophageal manometry confirming normal esophageal function, 10 patients changed into a standing position. Subjects were then instructed to take 10 breaths targeted towards the thorax, followed by 10 breaths with active abdominal breathing, followed by 10 breaths of abdominal breathing with increased airway resistance (compression of one nostril). In addition to standard manometric measurements, we analyzed the fraction of time in percent of pEGJ over 10, 15, 20, 25 and 30 mmHg. Manometric recordings of esophageal motor function were evaluated with the Manoview™ software. ANOVA and Post-Hoc tests were used for statistical analysis.

Results: During thoracic breathing p_maxEGJ (maximal pressure; median ± upper/lower quantile) showed normal values (39 mmHg ± 24/44) and significantly increased during abdominal breathing (62 mmHg; ± 52/85). Abdominal breathing with increased airway resistance did not show an additional effect (70 mmHg ± 63/92). During abdominal breathing with increased resistance the time of pEGJ over 20 mmHg, 25 mmHg and 30 mmHg was significantly longer compared to thoracic breathing (>20 mmHg: 44% (39/50) versus 76% (42/93); >25 mmHg: 38% (30/41) versus 57 % (36/69); >30 mmHg: 28% (19/33) versus 48% (33/63)).

Conclusion: Our study clearly shows that the type of breathing significantly influences pEGJ. In addition, we found that pEGJ reaches longer time intervals with competent pEGJ in abdominal compared to thoracic breathing. Current recommendations for routine esophageal analysis do not include breathing type. We suggest that breathing type should be taken into consideration when interpreting esophageal manometric data. We have already shown that controlled breathing training can improve symptoms in patients suffering from gastroesophageal reflux. Our current data suggests that a direct training effect on diaphragmal muscles might be an explanation for the findings of our previous studies.

Disclosure of Interest: None declared

P0504 OUTCOMES OF REDO SURGERY FOR FAILED LAPAROSCOPIC FUNDOPLICATION IN JAPANESE PATIENTS

F. Yano¹, N. Omura¹, K. Tsuboi¹, M. Hoshino¹, S. R. Yamamoto¹, S. Akimoto¹, T. Masuda¹, Y. Ishibashi¹, K. Nakada¹, N. Mitsumori¹, H. Kashiwagi¹, K. Yanaga¹

¹Surgery, The Jikei University School of Medicine, Tokyo, Japan

Contact E-mail Address: f-yano@jikei.ac.jp

Introduction: Laparoscopic fundoplication (LF) is an established surgical treatment for GERD. In our institution, about 95% of patients reported a high degree of satisfaction with surgery. On the other hand, some patients were expected to undergo redo surgery for reasons such as recurrence of hiatal hernia and/or reflux esophagitis.

Aims & Methods: The aim of this study was to investigate the outcomes of redo surgery for failed laparoscopic fundoplication in Japanese patients. Four-hundred and seventy-four patients underwent laparoscopic anti-reflux surgery between December 1994 and January 2015 in our institution. Among them, 11 patients who had redo surgery were studied. Their mean age was 57.7 ± 15.1 (range, 29-78) years, and 6 of them (45%) were female. Their clinical data were collected in a prospectively fashion and retrospectively reviewed. The outcomes were assessed in terms of indications for redo surgery, operative procedure, operation time, blood loss, perioperative complications, and postoperative course.

Results: No operative mortality occurred. The indications for surgery (some were overlapped) were dislocations of fundic wrap in 5 (45%), recurrence of paraesophageal hiatal hernia or erosive reflux esophagitis in 3 (27%) each, tight Nissen or esophageal motility disorder in 1 (9%) each. Ten (91%) were approached laparoscopically and another (9%) required conversion to open surgery. Eight (73%) underwent redo fundoplication, and the others underwent hiatal hernia repair alone. The mean operation time was 202 ± 46 (range 125-256) minutes and the mean blood loss was 56 ± 100 (range 0-292) ml. No patient required blood transfusion. Perioperative gastric wall injury was observed in 3 patients (27%). Almost all patients’ postoperative courses were uneventful and the median time to start postoperative oral intake and the median post-operative hospital stay were post-operative day 1 and 8, respectively. Three patients (27%) required prescription of proton pump inhibitors (PPIs) despite surgery and 2 patients (18%) had recurrence of hiatal hernia. Postoperative questionnaire was answered by 7 of 11 patients (74%). All patients reported full points 5 (range 1-5) as a satisfaction to surgery.

Conclusion: Redo surgeries for failed laparoscopic fundoplication were safely performed under laparoscopy. Recurrence rate after redo surgery was about 20% and more than 70% of patients could be withdrawn from PPIs.

Disclosure of Interest: None declared

P0505 PRELIMINARY RESULTS OF A PROSPECTIVE MULTI-CENTER OBSERVATIONAL REGISTRY OF LOWER ESOPHAGEAL SPHINCTER STIMULATION FOR GERD: THE LESS-GERD REGISTRY

H. G. Schulz¹, A. Leodolter², J. B. Pedersen³, E. Eypasch⁴, J. Labenz⁵

¹Zentrum für Minimal Invasive Chirurgie, Evangelisches Krankenhaus, Castrop-Rauxel, ²Internal Medcine, EvK Herne, Herne, Germany, ³surgery, Aarhus University Hospital, aarhus, Denmark, ⁴Heilig Geist-Krankenhaus Köln Longerich, Cologne, ⁵Internal Medcine and Gastroenterology, Diakonie Klinikum Jung-Stilling Krankenhaus, Siegen, Germany

Contact E-mail Address: j.labenz@t-online.de

Introduction: The electrical stimulation of the lower esophageal sphincter (LES-ES) using the EndoStim® LES Stimulation System (The Hague, The Netherland) was shown to be effective and safe in clinical trials. So far there no data was reported in routine clinical practice.

Aims & Methods: An ongoing, prospective multicenter web-based registry for the evaluation of LES-ES is prospectively collecting data at baseline and at routine follow-ups for 5-year on patient undergoing LES-ES in routine clinical practice for disruptive GERD symptoms despite daily PPI use. Demographics, adverse events, GERD symptoms using daily diaries and GERD health related quality of life score (GERD-HRQL) for reflux symptoms, structured GI symptom questionnaire for extra-esophageal symptoms, recorded use of proton pump inhibitors (PPIs) and objective endoscopic and physiological data (esophageal pH / manometry) when available.

Results: Currently, data from 46 enrolled patients is available in the registry, of whom 24 had data at 6 months post-op. All but one (23/24; 96%) patient showed an improvement in their GERD-HRQL score. Overall, the median (IQR) composite GERD-HRQL score of 21.5 (17.5-25.5) preoperatively improved to 6.5 (3.0-10.5) after 6 months (p <0.0001). The median distal esophageal acid exposure improved from 8.8 (3.4-18.5) % at baseline to 2.65 (1.6-5.1) % at 6 months (p=NS). The proportion of patients with moderate to severe regurgitation decreased from 72% on-therapy preoperatively to 29% after 6 months of LES-ES (p < 0.04). Bothersome reflux symptoms during sleep improved from 43% pre-op to 4% (p < 0.004) at 6 months. Recurrent cough decreased from 21% patients preoperatively to none after 6 months. One patient reported severe dysphagia pre-op that was resolved post-op. There was no change in the rate of occasional dysphagia reported. All patients were on long-term PPI at baseline. At 6 months, 17 (70%) patients were completely free of PPI use, 4 patients (17%) were still taking daily PPI and another 3 patients (13%) used PPI occasionally or had reduced their dose by > 50%. There were two serious adverse events (both resolved) classified as unrelated to device or procedure: acute pain from pre-existing gall-stones and intestinal atony occurring two weeks post-op. There were no GI side-effects related to the procedure or stimulation therapy reported.

Conclusion: LES-ES is safe and effective in routine clinical practice with improved quality of life and elimination of a PPI maintenance therapy in most patients. LES-ES may be considered a viable treatment option for well selected GERD patients with bothersome symptoms on PPI.

Disclosure of Interest: H. Schulz Financial support for research: EndoStim Inc., Consultancy: EndoStim Inc., A. Leodolter Financial support for research: EndoStim Inc., J. Pedersen: None declared, E. Eypasch Financial support for research: EndoStim Inc., J. Labenz Financial support for research: EndoStim Inc., Consultancy: EndoStim Inc.

P0506 INADEQUATE SYMPTOM CONTROL ON LONG-TERM PPI THERAPY IN GERD – FACT OR FICTION?

J. Labenz¹, G. M. Labenz², D. Stephan³, F. Willeke³, on behalf of LOPA Study Group

¹Internal Medicine & Gastroenterology, Diakonie Klinikum Jung-Stilling Krankenhaus, Siegen, ²Private Practice for Nutritional Medicine, Medizinisches Zentrum, Burbach, ³Surgery, Marienkrankenhaus, Siegen, Germany

Contact E-mail Address: J.Labenz@t-online.de

Introduction: Randomized controlled trials report about 30% of GERD patients complain of bothersome remaining symptoms (heartburn, regurgitation) despite PPI. General practice physicians estimate this to be an over-representation.

Aims & Methods: In a prospective, multicenter, observational study, which was conducted in 16 general practice clinics over 3 months, patients with GERD and taking PPI for over 1 year were asked to complete a questionnaire. Patients were asked the duration of their GERD, duration of PPI therapy, satisfaction with their condition on PPI, whether they have received diagnostic evaluation related to GERD (endoscopy, pH monitoring, manometry), whether they have received surgical consultation for GERD, and the frequency of any remaining complaints in the past week (i.e. heartburn, regurgitation, sleep disruption) as part of a validated questionnaire for the diagnosis of GERD (GerdQ). “Lost Patients” were defined as those likely to be suffering from true GERD as predicted by the GerdQ questionnaire, dissatisfied on their current PPI therapy, and had not previously received any specific GERD diagnostics (pH-metry or manometry).

Results: 323 consecutive patient responses were collected. Patients suffered from GERD for an average of 8.42 years and prescribed PPI therapy for an average duration of 6.26 years. 39% of patients reported heartburn at least 2 days per week (20% 4-7 days per week), 29% complained of regurgitation at least 2 days per week (13% 4-7 days per week), and 22% reported symptoms disrupting sleep at least twice per week (7% 4-7 days per week). 20% of patients were dissatisfied on their current PPI therapy (score of 1 or 2 on a scale of 1-5, 1=very dissatisfied, 5=very satisfied), and 13% were both dissatisfied and had a high likelihood of complaints correlating to pathological pH based on the GerdQ questions. A total of 85% of patients received an upper endoscopy in the past, but only 7% had a prior pH-metry and 2% manometry. Only 7% received prior surgical consult for GERD. The rate of “Lost Patients” was 10%.

Conclusion: Inadequate control of symptoms is common in GERD patients prescribed PPI therapy, and is often overlooked in daily practice. These patients with insufficient symptom control should be methodically identified and considered for further diagnostics and/or treatment modification, for example with a screening questionnaire.

Disclosure of Interest: None declared

P0507 GLOBAL CLINICAL EXPERIENCE WITH ENDOSTIM® LOWER ESOPHAGEAL SPHINCTER STIMULATION THERAPY: AN INDIVIDUAL PATIENT DATA META-ANALYSIS OF THE OPEN LABEL CLINICAL TRIALS

S. E. Attwood¹, G. I. Leontiadis², L. Rodriguez³, P. D. Siersema⁴, J. Labenz⁵

¹Surgery, Northumbria Healthcare and Durham University, North Tyneside, United Kingdom, ²Department of Medicine, Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada, ³Centro Clínico de Obesidad, Santiago, Chile, ⁴Gastroenterology and Hepatology, UMC Utrecht, Utrecht, Netherlands, ⁵Internal Medicine & Gastroenterology, Diakonie Klinikum Jung-Stilling Krankenhaus, Siegen, Germany

Contact E-mail Address: stephenattwood@onetel.com

Introduction: Electrical Stimulation of the LES is emerging as a new theraputic modality for refractory GERD

Aims & Methods: To assess efficacy and safety of LES stimulation in GERD patients by performing an individual patient data meta-analysis.

A systematic literature search and contact with EndoStim confirmed that no additional clinical trials on LES stimulation in GERD patients other than the two open-label clinical trials were available ^[1,2]. The individual patient data from the 2 trials were used for this meta-analysis after it was shown that the two trials had identical design, with no significant differences in the baseline inclusion and exclusion criterial of the trials, and no heterogeneity in baseline and follow-up summary data. Each patient’s baseline data was used as control data and 6-month data was used as on-treatment data.

Results: Sixty-six patients, with 43% women at 11 centers in Europe, South America and Asia, were included. Median age was 52 (IQR=43-62) years. Ninety-five percent (63/66) of patients were using daily PPIs with one-third of them using PPIs twice daily. At their 6 months follow-up, 89% (58/65) were no longer using PPIs and 5% (3/65) were using PPIs on < 50% of days. Median distal esophageal acid exposure at baseline was 10.0% (IQR=7.7-12.9), which had improved to 4.9% (IQR=2.4-7.3) % at 6 months follow-up (p < 0.001). Median GERD-HRQL scores at baseline on-PPI were 10 (IQR 8-21) and off-PPI 28 (IQR 22-34) which improved to 4.0 (IQR 1-9) at 6 months on LES stimulation therapy (p < 0.001 vs. both on and off-PPI). Significant improvement in median days with heartburn and regurgitation at day and night vs. baseline both on- and off-PPI (p < 0.001), and near-complete elimination of regurgitation and nocturnal symptoms were observed. There were no statistically significant differences in efficacy outcomes between geographical locations (Europe vs. South America vs. Asia). In total, 2 SAEs related to the device or procedure (trocar perforation and asymptomatic lead erosion) were managed with device explant. There were 65 device and/or procedure-related non-serious adverse events, all typical of a laparoscopic implant procedure and resolving without any invasive intervention.

Conclusion: This meta-analysis confirms the results of previous trials on safety and efficacy of LES electrical stimulation in GERD patients and provides a robust estimate of the effect size among a larger number of patients and across multiple geographical locations.

Disclosure of Interest: S. Attwood Consultancy: EndoStim Inc., G. Leontiadis: None declared, L. Rodriguez Financial support for research: EndoStim Inc., P. Siersema Financial support for research: EndoStim Inc., Consultancy: EndoStim Inc., J. Labenz Financial support for research: EndoStim Inc., Consultancy: EndoStim Inc.

P0508 ASSOCIATION OF SLEEP DISTURBANCES WITH SPECTRUM OF GASTRO-OESOPHAGEAL REFLUX DISEASE IN A CHINESE GENERAL POPULATION

P.-H. Tseng¹, Y.-C. Lee¹, H.-M. Chiu¹, W.-C. Liao¹, C.-C. Chen¹, C.-H. Tu¹, P.-L. Lee¹², C.-K. Peng³, M.-S. Wu¹, on behalf of Taiwan GI disease, and Helicobacter. consortium

¹Internal Medicine, ²Sleep Center, National Taiwan University Hospital, Taipei, Taiwan, Province of China, ³Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States

Contact E-mail Address: pinghuei@ntu.edu.tw

Introduction: Previous studies have shown a complex relationship between sleep disturbances and gastro-oesophageal reflux disease (GORD). Since GORD could be further categorized into subgroups based on the endoscopic findings and the presence of typical reflux symptoms, whether the GORD spectrum are associated with different impact on the sleep quality remains unclear.

Aims & Methods: We aim to investigate the association of subjective and objective sleep disturbance with the heterogeneous manifestations of GORD in a Chinese general population. We prospectively recruited 561 subjects who voluntarily underwent an electrocardiogram-based cardiopulmonary coupling analysis as part of a comprehensive health check-up at the National Taiwan University Hospital during 2012-2013. All subjects received the Reflux Disease Questionnaire (RDQ) and an upper endoscopy to determine the presence of erosive oesophagitis (EO) and non-erosive reflux disease (NERD), defined as subjects with troublesome symptoms (a heartburn/regurgitation score >3 by RDQ) but without definite endoscopic mucosa breaks. Subjective sleep quality was evaluated with the Pittsburgh Sleep Quality Index (PSQI) and sleep dysfunction was defined as a PSQI >5. Sleep-disordered breathing was defined as the apnoea–hypopnoea index derived from the cardiopulmonary coupling analysis >15 event/hour. Detailed demographics, anthropometrics, metabolic profile and psychological status were also obtained. Comparisons were made between subjects with and without GORD and subjects within the different categories of GORD spectrum for a range of subjective and objective sleep parameters.

Results: Of the 277 subjects (49.4%) who were diagnosed as having GORD, EO was found in 198 subjects (35.3%), in whom 123 (21.9%) were symptomatic and 75 (13.3%) were asymptomatic (RDQ=0). NERD was diagnosed in 79 subjects (14.1%). Subjects with GORD had higher global PSQI scores (6.99 ± 3.97 vs. 6.07 ± 3.73, P=0.005) and a higher prevalence of sleep dysfunction (60.6% vs. 49.6%, P=0.009) than those without GORD. Subjects with EO had a significantly higher prevalence of sleep-disordered breathing than those without (42.9% vs. 33.9%, P=0.034). Presence of troublesome reflux symptoms was independently associated with sleep dysfunction in the multivariate analysis (adjusted odds ratio = 2.05; 95% confidence interval=1.39-3.00). Across the GORD spectrum, subjects with symptomatic EO had the highest PSQI scores (7.68 ± 3.93) as well as the prevalence of sleep dysfunction (70.7%), while the prevalences of sleep-disordered breathing among the subgroups were not significantly different.

Conclusion: We demonstrated a high prevalence of subjective and objective sleep disturbances among the GORD patients in this Chinese population. Different manifestations across the GORD spectrum were associated a variety of impairment on the sleep quality. Further interventional studies to explore the effect of aggressive GORD treatment on the various aspects of sleep quality of GORD patients are warranted.

Disclosure of Interest: None declared

P0509 OUTCOME OF ESOPHAGO-GASTRIC JUNCTIONAL ADENOCARCINOMA TREATED BY ESD

A. Takahashi¹, T. Oyama¹

¹Endoscopy, Saku Central Hospital Advanced Care Center, Nagano, Japan

Introduction: Esophago-gastric junctional adenocarcinoma (EGJAC) was rare in Japan. However, recently the incident of EGJAC has been increasing. And the outcome of endoscopic submucosal dissection (ESD) for EGJAC is unknown.

Aims & Methods: The aim of study is to investigate the outcome of EGJAC treated by ESD.

EGJAC was defined as adenocarcinoma located between 1cm oral and 2cm anal from EGJ. 92 patients (80 males and 12 females) with EGJAC were treated by ESD from January, 2000 to December, 2011. Follow up examination including annual CT and EGD was performed. R0 resection rate, complications and prognosis were investigated. Additional therapy was recommended for the T1bSM2 (501 micrometer or deeper) patients. The median age and follow up period was 74 (32-89) and 65 (6-173) months, respectively. The median diameter of the resected lesions and specimens was 18 (3-61) and 40 (20-82) mm, respectively. Protuberant, flat and depressed type was 44, 4 and 44 lesions, respectively. Differentiated and poorly differentiated adenocarcinoma was 88 and 4 lesions, respectively.

Results: 1. Complete resection rate was 100%. R0 rate resection was 99% (91/92).

2. Complications: The bleeding during ESD and delayed bleeding required blood transfusion was 0% and 1% (1/92). The perforation during ESD and delayed perforation was 1% (1/92) and 0%. Stenosis was 11% (10/92), and all of 10 cases were treated by endoscopic balloon dilatation.

3. T1a-M, T1b-SM1(less than 500 micrometer) and T1bSM2 was 62, 15 and 15 lesions, respectively.

4. Local recurrence rate was 0% in any groups.

5. Prognosis.

5-1 T1a-M and T1b-SM1: No patient died of EGJAC.

5-2 T1bSM2: Additional gastrectomy was performed for 7 of 15 T1b-SM2. And, only one case had lymph node metastasis. 7 patients were followed up without gastrectomy. One patient was treated by additional radiation, and lymph node metastasis was found after radiation. Only this patient died of EGJAC.

Conclusion: T1a-M and T1bSM1 EGJAC are good candidate for ESD. However, additional therapy should be recommended for T1bSM2 EGJAC patients.

Disclosure of Interest: None declared

P0510 FEASIBILITY AND USEFULNESS OF EUS-FNA IN THE DIFFERENTIAL DIAGNOSIS BETWEEN MALIGNANT AND BENIGN LESIONS FOR RELATIVELY SMALL DUODENUM SUBMUCOSAL TUMORS

A. Aso¹, E. Ihara¹, K. Nakamura¹, T. Osoegawa¹, A. Goto¹, T. Iwasa¹, T. Ito¹, Y. Oda²

¹Medicne and Bioregulatory Science, ²Anatomic Pathology, Kyushu Univercity, Fukuoka, Japan

Contact E-mail Address: miro1124@gmail.com

Introduction: Duodenal submucosal tumors (SMTs) with malignant potentials including gastrointestinal stromal tumors (GIST) are relatively rare, but we sometimes need to make a differential diagnosis of duodenal SMTs. Although it is generally accepted that EUS-FNA is a gold standard for making a histological diagnosis of gastric SMTs, the feasibility and usefulness of EUS-FNA for duodenal SMTs have yet to be determined. In general, tissue sampling of duodenal SMTs by EUS-FNA is more difficult than that of gastric SMTs.

Aims & Methods: The aims of the present study were to assess feasibility, safety, and usefulness of EUS-FNA for duodenal SMTs. Between June 2009 and March 2015, a total of 17 patients with duodenal SMTs who had undergone EUS-FNA were enrolled in the present study and were retrospectively reviewed. A linear EUS scope (UCT260-AL5; Olympus, Tokyo, Japan) together with needle devices (22G, 25G) were used for EUS-FNA with rapid on-site evaluation (ROSE). We evaluated success rate of sampling, diagnostic yield and procedure-related complications.

Results: The mean diameter of duodenal SMTs was 22.4 mm in size ranging from 8 to 59 mm. The puncture could be completed in all 17 patients. The mean number of FNA passes was 3.8 ranging from 1 to 7. All samples were satisfactory for making a histological diagnosis. As a result, ten patients were diagnosed with GIST, one with gangliocystic paraganglioma, one with neuroendcrine tumor and five with benign tumors. There were no procedure-related complications. Although most samples obtained by EUS-FNA in the present study were smaller than those usually obtained with gastric SMTs, we could make a differential diagnosis between malignant tumors and benign lesions in all cases.

Conclusion: This is the first case series showing feasibility of EUS-FNA for relatively small duodenal SMTs. EUS-FNA could be a useful diagnostic tool for surgical decision making not only in gastric SMTs but also in duodenal SMTs.

Disclosure of Interest: None declared

P0511 LONG-TERM GASTRIC CANCER RISK IN SMOKING MEN WITH ATROPHIC GASTRITIS

A. Nieminen¹², P. Sipponen¹², J. Kontto³, P. Puolakkainen¹², J. Virtamo³, A. Kokkola¹²

¹Department of Surgery, Helsinki University Hospital, ²Helsinki University, ³National Institute for Health and Welfare (THL), Helsinki, Finland

Contact E-mail Address: anna.a.nieminen@hus.fi

Introduction: The incidence of gastric cancer has declined dramatically during last decades in western countries. In Finland, the age-standardized incidence being 6.3 / 100 000 for men and 3.6 / 100 000 for women ¹. Because of the low incidence, screening programs are not considered effective in the West. Early gastric cancer rarely causes symptoms, and, thus majority of gastric cancers are diagnosed in advanced, symptomatic stage.

Atrophic gastritis in the best known premalignant condition of gastric cancer, and it has been suggested that persons who have extensive atrophic changes in stomach should undergo surveillance.

Aims & Methods: Our aim was to evaluate the long-term gastric cancer risk in smoking men with atrophic gastritis.

Serum pepsinogens (SPGs) were measured from 22,436 smoking men (age 50-69 years) who participated The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study in Finland ^2-3. Low serum pepsinogen I (SPGI) was measured in 2132 men, and they were invited to gastroscopy ⁴. Endoscopy was performed to 1344 men, and after excluding the men with gastric cancer in a beginning of study, 1326 men were enrolled in this study.

The first gastroscopies were performed between years 1989-1993, and the surveillance continued until the end of year 2012, the gastric cancer diagnosis, or the death. The median follow-up time was 13.6 years (range 16 days – 23.3 years). Thirty three gastric cancers were diagnosed during the follow-up period.

Results: Most of the men (80.2%) had atrophic gastritis of some degree in the histological samples of the corpus (mild 11.4%, moderate 41.7%, marked 27.1%). Atrophic gastritis of the antrum was found only in 34.0% of the subjects. Mild to marked intestinal metaplasia appeared in 66.5% patients in corpus and 40.1% in antrum.

The gastric cancer incidence was 1.89 / 1000 patient-years. The incidence of gastric cancer increased as the grade of the atrophy of the corpus mucosa increased: 1.54/1000, 1.77/1000, and 2.05/1000 in mild, moderate, and severe mucosal corpus atrophy, respectively. In the antrum mucosa, the effect of the degree of the atrophy had similar effect on the gastric cancer incidence: 2.16/1000, 2.21/1000, and 3.44/1000 in mild, moderate, and severe atrophy.

The gastric cancer incidence was 1.35/1000, 2.27/1000, and 2.84/1000 in mild, moderate, and severe corpus intestinal metaplasia (IM), respectively. In the antrum, the incidence of gastric cancer was 1.87/1000, 2.23/1000, and 3.99/1000, in mild, moderate, and severe IM, respectively.

Conclusion: The risk of gastric cancer increased as the grade of the mucosal atrophy and intestinal metaplasia increased. The risk of gastric cancer seems to be within limits of previous publications (0.1-0.2% person years).

Disclosure of Interest: None declared

P0512 OLGA AND OLGIM STAGING SYSTEMS IN MEN WITH ATROPHIC GASTRITIS

A. Nieminen¹², P. Sipponen¹², J. Kontto³, P. Puolakkainen¹², J. Virtamo³, A. Kokkola¹²

¹Department of Surgery, Helsinki University Hospital, ²Helsinki University, ³National Institute for Health and Welfare (THL), Helsinki, Finland

Contact E-mail Address: anna.a.nieminen@hus.fi

Introduction: Intestinal type of gastric cancer develops through precancerous changes, but minority of these changes progress to cancer. Endoscopical surveillance is allocated for patients with extensive gastric atrophy or intestinal metaplasia. To target endoscopy for high-risk patients, two staging systems (Operative Link for Gastritis Assessment [OLGA]¹ and Operative Link on Gastric Intestinal Metaplasia Assessment [OLGIM]²) have been created. The focus is on severity and topography of atrophy and intestinal metaplasia.

Aims & Methods: In our scope was to investigate the predictive value of OLGA and OLGIM staging systems in smoking males with atrophic gastritis.

Serum pepsinogens (SPGs) were measured from 22,436 smoking men, aged 50-69 years, who participated The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study ³ in Finland. Low serum pepsinogen I (SPGI) was measured in 2132 men, and they were invited to gastroscopy ⁴. Endoscopy was performed to 1344 men, and after excluding the men with gastric cancer in a beginning of study and 180 men with history of gastric surgery by benign cause, 1146 men were enrolled in this study.

The first gastroscopies were performed between years 1989-1993, and the surveillance continued until the end of year 2012, the gastric cancer diagnosis, or the death. The median follow-up time was 13.7 years (range 16 days – 23.3 years). Twenty seven gastric cancers were diagnosed during the follow-up period.

Results: Gastric cancers (n=27) distributed by OLGA stages following: 1, 3, 17, 1, and 5 (stages 0-IV, respectively), and OLGIM stages: 2, 7, 10, 4, and 4 (stages 0-IV, respectively). By OLGIM staging system, gastric cancer risk elevated with stages (p=0.02). The trend was not as distinct with OLGA staging (p=0.10). Three gastric cancers developed to patients with OLGA / OLGIM stage 0, and histological type was known in only one of these patients, who had diffuse type of cancer.

Conclusion: Interobserver agreement is excellent with intestinal metaplasia, but weaker with atrophy and dysplasia ^2,5. Also in our study, OLGIM was more sensitive to predict gastric cancer risk over OLGA. Histological type can confound the interpretation, as cancerous cascade with atrophy and intestinal metaplasia are illustrated with intestinal, not diffuse, type of gastric cancer.

Disclosure of Interest: None declared

P0513 PREDICTIVE FACTORS FOR RESPONSE TO NEO-ADJUVANT CHEMOTHERAPY IN PATIENTS WITH RESECTABLE GASTRIC CANCER

C. Palmela¹, A. O. Ferreira¹, F. Branco², M. Santos³, M. P. Costa Santos¹, H. Oliveira⁴, R. Seruca⁵, R. Garrido³, T. Rodrigues², J. A. Teixeira², R. Maio³, M. Cravo¹

¹Gastrenterology, ²Oncology, ³General Surgery, ⁴Pathology, Hospital Beatriz Ângelo, Loures, ⁵IPATIMUP, Porto, Portugal

Contact E-mail Address: palmela.carolina@gmail.com

Introduction: Neo-adjuvant chemotherapy (CT) has been shown to improve survival in locally advanced gastric cancer. It has been suggested that the clinical outcome is associated with preoperative down staging. CT is also associated with toxicity and poor patient tolerance.

Aims & Methods: Our aim was to identify predictive factors of response to perioperative CT. We conducted a prognostic study using an academic centre retrospective cohort of patients with gastric adenocarcinoma diagnosed between January 2012-December 2014 and submitted to perioperative CT. Response to pre-operative CT was evaluated by radiologic criteria and on the surgical specimen. We built a prognostic model using logistic regression analysis including demographic, clinical and morphological characteristics. Explanatory variables were kept when p < 0.20.

Results: A total of 160 patients were diagnosed of which 42 were submitted to perioperative CT. Mean age was 68 ± 10 years-old, 28 (67%) were male. Esophagogastric junction was involved in 5 (12%), gastric body in 19 (45%) and antrum in 18 (43%). The histology was intestinal type in 31 (74%) and diffuse in 11 (26%). ECF/EOX was used in 34 (81%) and FOLFOX/XELOX in 8 (19%). Response was observed in 30 (71%) with complete pathological response in 3 (7%). Toxicity was reported in 27 (64%) cases with interruption in 16 (38%). Median follow-up was 15.5 months (IQR 8.75-19.25). Mortality was 15 (35.7%). The final model included the following predictors: age (OR 0.898, CI 0.787-1.024; p=0.109), female gender (OR 27.676, CI 0.679-1127.883; p=0.079), poor CT tolerability (OR 0.115, CI 0.028-0.468; p=0.002) and gastric body tumor (OR 0.071, CI 0.005-0.989; p=0.049) were included in the model. The AUROC for the model was 0.943. Histological type, microsatellite instability and E-cadherin immunoexpression didn’t show association with response to CT.

Conclusion: Increasing age, male gender, poor CT tolerability and gastric body location were independent predictors of non-response. Our model was able to accurately predict pre-operative CT response. Prospective evaluation is warranted before clinical application.

Disclosure of Interest: None declared

P0514 RELATIONSHIP BETWEEN GASTROPANEL AND O.L.G.A IN THE DETECTION OF CHRONIC ATROPHIC GASTRITIS IN A PRIMARY CARE SETTING

E. Goni¹, M. Franceschi², C. Scarpignato¹, M. Rugge³, F. Di Mario¹

¹Department of Clinical and Experimental Medicine, University of Parma, Parma, ²Endoscopic Unit - Department of surgery, ULSS4 - Alto Vicentino, Santorso, Vicenza, ³Department of Pathology, University of Padua, Padova, Italy

Contact E-mail Address: elisabetta.goni@gmail.com

Introduction: Chronic Atrophic Gastritis (CAG) is the most important independent risk condition for gastric cancer, histology being considered the gold standard for both diagnosis and follow up. The Operative Link for Gastritis Assessment (O.L.G.A) is an innovative histological system proposed for staging atrophic gastritis in a prognostic view.

GastroPanel^® (Biohit, Helsinki, Finland) is a serological kit for a non-invasive diagnosis of chronic atrophic gastritis (CAG), including serum pepsinogen I (PGI), pepsinogen II (PGII), gastrin-17 (G-17) and IgG anti-Helicobacter pylori antibodies (IgG-H.p.).

Clinical practice is lacking of a non invasive instrument useful to predict and to follow the stage of atrophic gastritis.

Aims & Methods

Aim: To evaluate correlation between GastroPanel^® and O.L.G.A stage, in a cohort of dyspeptic patients referred from a primary care setting.

Subjects and Methods: Histological evaluation of gastric biopsies was performed in 249 patients (M=129, mean age 49 years, range 21-79 years). Atrophy was assessed according to the O.L.G.A staging system.

O.L.G.A stages III and IV are considered at high risk for gastric cancer development. From each subject, a blood sample was taken for GastroPanel^® analysis.

Results: GastroPanel^® analysis showed that 82 patients were normal (mean age 46 years, range 21-64 years, M= 49), 116 patients had a H.p.-related chronic gastritis (mean age 54 years, range 35-79 years, M= 68) and 51 had atrophic gastritis picture (mean age 61 years, range 21-79 years, M= 22).

Comparing GastroPanel^® results to the histological findings, 77 patients had an O.L.G.A stage 0-II, 4 pts have an OLGA stage III, 1 stage IV.

Among the patients with Hp-related gastritis, 112 patients had an O.L.G.A stage 0-II, 3 patients had an O.L.G.A stage III and 1 patient had O.L.G.A stage IV.

Twenty-two out of the 51 patients with evidence of CAG at GastroPanel^® had an O.L.G.A stage 0-II, 29 patients had an O.L.G.A stage III-IV. The negative predictive value (NPV) of GastroPanel^® for CAG is 95,0%, being the positive predictive value (PPV) 75,0%.

O.L.G.A
Gastropanel®	0	I	II	III	IV
Normal values	46	17	14	4	1
H.p.-related gastritis	51	23	38	3	1
Chronic atrophic gastritis	1	5	16	19	10

Conclusion: GastroPanel^® showed an high NPV to predict absence of atrophic gastritis.

The relationship beetween GastroPanel and O.L.G.A system seems to confirm the clinical performances of the test.

Disclosure of Interest: None declared

P0515 ENDOSCOPIC BAND LIGATION WITHOUT RESECTION IN SELECTED PATIENTS FOR SMALL AND SUPERFICIAL UPPER GASTROINTESTINAL TRACT LESIONS

G. Ibáñez¹, J. B. Gornals¹, L. Rivas¹, S. Salord¹, M. J. Paúles¹, M. C. Galán²

¹Hospital Universitari Bellvitge-Idibell, ²Institut Català d'Oncologia DiR-Idibell, Barcelona, Spain

Contact E-mail Address: jgornals@bellvitgehospital.cat

Introduction: Band ligation with electrosurgery of early small lesions of upper gastrointestinal (UGI) tract (dysplasia or T1a-b) or subepithelial tumors (neuroendocrine tumors (NETs) are associated with complications especially in duodenal lesions.

Aims & Methods: The aim of this study is to investigate the efficacy and safety of endoscopic band ligation (EBL) without electrosurgery in selected patients where surgery is contraindicated. Twelve patients from 2010 through 2015 with early UGI (upper gastrointestinal) lesions treated with EBL for autoamputation (1.83 rubber bands/session) were included prospectively and analyzed retrospectively. All were discussed in a UGI multidisciplinary cancer committee where it was concluded that owing to patient’s conditions surgery was not possible and that not getting histology would not change the clinical management. Before the procedure, a CT and/or radial echoendoscope was performed. In flat lesions (Paris Classification: Is-IIa) chromoendoscopy with spray catheter and argon plasma coagulation were used to delimit the margins before the banding. With a Duette® Multi-Band Mucosectomy device the rubber bands were deployed. Second endoscopy with biopsies was planned in 4-8weeks. If there was no persistence of the lesion, a new control was programmed at 6 and then at 12 months. On the contrary, if there was histologic persistence a new treatment was applied.

Results: The group included 5 esophagus lesions (adenosquamous carcinoma (n=1); carcinoma squamous (n=2); adenocarcinoma (n=2)); 4 gastric lesions (high grade dysplasia (n=1); adenocarcinoma (n=2); NET (n=1)) and 3 duodenal lesions (NET (n=3)). The mean tumor diameter was 9.3+/-3.7mm (range 4-17.5). Only 1 adverse event in one patient was described, which was mild chest pain. Observation for 8 hours was possible in all patients except in 2 cases. After a median of 7 weeks the treatment, there was endoscopic remission in 92% (n=11/12) and histologic remission in 75% (n=9/12). In the 6-month biopsies, there were 70% (n=7/10) of negative biopsies and in the 12 months 80% (n=4/5). The persisting lesions were T1 cancers (T1 esophagus (n=3), T1 stomach (n=1)) but with a new EBL two of the T1 cancers got negative biopsies in the next endoscopy. The median follow-up is of 20.9 months (range 5.9-60 months).

Abstract number: P0515

	Age, years	Sex	Comorbidity
1	83	M	Asthma, ischemic heart disease, peripheral vascular disease, low social support
2	59	M	Lung cancer in treatment, previous ORL cancer, esophageal stricture, trismus
3	68	M	Decompensated cirrhosis, COPD, peripheral vascular disease
4	77	F	Atrial fibrillation, cerebrovascular accident
5	82	F	Cognitive disorder, previous gastric ADK (Billroth I)
6	75	M	Previous oral carcinoma, intestinal ischemia twice
7	83	F	Asthma, ischemic optic neuropathy
8	80	M	Atrial fibrillation, pituitary adenoma, monoclonal gammopathy
9	69	F	Previous intestinal resection
10	77	F	Decompensated cirrhosis, hepatocellular carcinoma, systemic lupus erythematosus, vaginal cancer, peripheral vascular disease
11	76	F	Cognitive disorder, atrial fibrillation, previous, breast cancer
12	62	M	Decompensated cirrhosis, COPD

Conclusion: EBL without electrosurgery is an easy and safe technique that should be considered in patients with multiple morbidities.

Disclosure of Interest: None declared

P0516 ENDOSCOPIC RESECTION OF DUODENAL NEUROENDOCRINE TUMORS: A CASE SERIES OF A SINGLE INSTITUTION

G. Fiori¹, D. Ravizza¹, C. Trovato¹, G. De Roberto¹, I. Bravi¹, C. Genco¹, L. Bottiglieri², C. Crosta¹

¹Division of Endoscopy, ²Division of Pathology, European Institute of Oncology, Milan, Italy

Contact E-mail Address: giancarla.fiori@ieo.it

Introduction: Duodenal neuroendocrine tumors (dNETs) are rare, being 1-3% of all primary duodenal tumors. With the widespread use of upper GI endoscopy, these tumors have been increasingly recognized.

Duodenal NETs not located in the periampullary region are suitable for endoscopic treatment if limited to the submucosal layer, without metastases and with a diameter less than 10 mm. Nevertheless, few data are available concerning the efficacy of this approach.

Aims & Methods: We reviewed our data about dNETs treated with endoscopic resection (ER).

Results: From January 2012 to December 2014, 11 dNETs were diagnosed during upper GI endoscopy. Five tumors underwent ER whereas 6 did not because of the presence of metastases (n=2), patient’s comorbidities (n=1), papillary location (n=1) and surgical treatment (n=1).

ER was performed with a high definition single-channel endoscope (EG29i series, Pentax). The resection technique was chosen according to the endoscopist’s preference, morphological characteristics, site and endosonographic features of each lesion. En-bloc resection was obtained in all cases. Endoscopic mucosal resection (EMR) was used for 3 bulb tumors and endoscopic submucosal dissection (ESD) for one bulb tumor. One tumor of the duodenal third part was treated with Hybrid-ESD (HESD). In 4 cases the resection site was closed with metal clips. The mean size of resected specimens was 14 mm (range 7-22 mm); histologically the tumor mean size was 9 mm (range 5-12 mm). The invasion depth was limited to the submucosal layer. Lateral or deep edge involvement occurred in 2 cases (one tumor treated with EMR and one with HESD). All lesions were well-moderately differentiated tumors with less than 1-2 mitosis per high power field. Ki67 proliferation index was 2-4% in 4 tumors and 16% in one.

One immediate perforation occurred and was treated conservatively. No patient underwent a second ER or surgical treatment. The mean follow up period was 17 months (range 6-31 months). No local recurrence was observed during endoscopic follow-up. A liver metastasis was detected at CT-scan one year after resection in one patient.

Conclusion: ER in the duodenum has a higher incidence of complications than in other sites of gastrointestinal tract because of the thickness duodenal wall. In order to avoid delayed perforation and bleeding, all resections except one, were treated with clips. Despite en-bloc resection was obtained in all cases, a complete pathological resection was confirmed in only 60% of cases. We suppose that such incomplete pathological resection is due to the paucity and laxity of submucosal duodenal tissue, which is destroyed during resection. In fact, because of the narrow duodenal lumen, can be technically difficult to avoid excessive burning of the peritumoral submucosal duodenal tissue. To support this hypothesis we did not observe any local recurrence at follow-up endoscopy. Our experience, although limited and retrospective, confirms the safety and efficacy of ER for the treatment of dNETs limited to the submucosal layers. However, additional studies with longer follow up are needed.

Disclosure of Interest: None declared

P0517 THE COMBINATION OF SERUM TREFOIL FACTOR 3 AND PEPSINOGEN TEST IS AN EFFECTIVE BIOMARKER FOR EARLY DETECTION OF GASTRIC CANCER

H. M. Yang¹, S. W. Jeon¹, H. S. Lee¹, S. Nomura²

¹Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea, ²Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

Contact E-mail Address: sw-jeon@daum.net

Introduction: The serum pepsinogen test has been used as a non-invasive biomarker for gastric cancer screening in Japan. However, there are limitations of its predictive power.

Aims & Methods: We aimed to investigate whether the combination of serum trefoil factor 3 (TFF3) and pepsinogen test could be an effective biomarker of gastric cancer screening. Two hundred and eighty-one gastric cancer patients who underwent endoscopic submucosal dissection in Korea were enrolled. And serum was collected from 708 healthy individuals without cancer in Japan. Serum levels of TFF3 were examined by enzyme-linked immunosorbent assays. Serum levels of pepsinogen I and pepsinogen IIwere measured using a latex-enhanced turbidimetric immunoassay.

Results: The mean serum TFF3 concentration in patients with gastric cancer was 9.36 ± 4.67 (95%CI [8.86,9.96]). For the prediction of gastric cancer presence, the area under the receiver-operating characteristic curve of TFF3 was 0.7489. Using cutoff of 6.728 ng/ml, patients with gastric cancer were detected with 80.4% sensitivity, and 57.3% specificity by the TFF3 test. One hundred and seventy-one of 281 patients were not identified as bearing gastric cancer with pepsinogen test. However, adding TFF3 test to the pepsinogen test, 136 of these 171 patients who were not identified by pepsinogen test could be detected by the TFF3 test. If the TFF3 was added to the pepsinogen test, the sensitivity (87.5%) for gastric cancer prediction was superior to the sensitivity (39.1%) of the pepsinogen test.

Conclusion: The combination of the serum TFF3 and pepsinogen test could be an effective non-invasive biomarker for gastric cancer screening.

Disclosure of Interest: None declared

P0518 CLINICAL OUTCOMES OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR SUBMUCOSAL INVASIVE EARLY GASTRIC CANCER

H. Suzuki¹, S. Maeda¹

¹Department of Gastroenterology, Sapporo Kosei General Hospital, Sapporo, Japan

Contact E-mail Address: suzukihajimeja@yahoo.co.jp

Introduction: The Japanese Gastric Cancer Association has proposed expanded criteria for the curative endoscopic resection of early gastric cancer as follows: a) differentiated intramucosal tumour without ulceration or scarring; b) differentiated intramucosal adenocarcinoma with ulceration or scarring, tumour ≤3 cm; c) differentiated adenocarcinoma with minimal submucosal invasion (SM1: ≤500 µm from the muscularis mucosae), ≤3 cm; and d) undifferentiated intramucosal adenocarcinoma without ulceration or scarring, ≤2 cm. However, it remains controversial whether endoscopic submucosal dissection (ESD) for submucosal invasive early gastric cancer (SM-EGC) is feasible or not.

Aims & Methods: The aim of our study was to assess the feasibility of ESD for SM-EGC. We retrospectively collected clinical data of 1030 consecutive patients with 1304 gastric lesions who had undergone ESD at our hospital between January 2005 and March 2015. Of these, 179 lesions (13.7%) were classified as SM-EGC by pathological evaluation using the ESD specimen; 87 lesions (48.6%) had submucosal invasion of less than 500 µm (SM1-EGC), and the remaining 92 lesions (51.4%) had invasion of 500 µm or more (SM2-EGC).

Results: There were no significant differences in patient age, gender, location, and histology or morphological type between patients with SM1-EGC and SM2-EGC. Tumour size in SM1-EGC and SM2-EGC was 19.8 ± 11 cm and 26.7 ± 16 cm, respectively (p < 0.005). Lymphovascular involvement was found in 13 patients with SM1-EGC (14.9%) and 49 patients with SM2-EGC (53.3%) (p < 0.005). The complete resection rates for SM1-EGC and SM2-EGC were 87.4% and 60.8%, respectively (p < 0.005). The procedure time for SM1-EGC and SM2-EGC was 74.6 ± 47 min and 101.9 ± 63 min, respectively (p < 0.005). There were no significant differences in post-procedure bleeding rate (6.9% vs. 6.5%) and perforation rate (4.6% vs. 6.5%). Twenty-three SM1-EGC patients (26.4%) underwent surgical resection after ESD as an additional treatment, and lymph node metastasis was found in only 1 case with lymphatic invasion. Additional surgical resection was performed for 63 patients (68.5%) of SM2-EGC patients, and lymph node metastasis was observed in 8 of these patients. Of 29 patients who did not undergo additional curative surgical resection, 2 patients with SM2-EGC had recurrence of lymph node metastases and underwent surgery, but no patient with SM1-EGC had lymph node metastases or local recurrence.

Conclusion: ESD for SM-EGC based on expanded criteria may be feasible, but additional long-term follow-up data are needed.

Disclosure of Interest: None declared

P0519 CLINICOPATHOLOGIC FEATURES OF GASTRIC CANCER WITH SYNCHRONOUS AND METACHRONOUS COLORECTAL CANCER IN KOREA: ARE MICROSATELLITE INSTABILITY AND P53 OVEREXPRESSION USEFUL MARKERS FOR PREDICTING COLORECTAL CANCER IN GASTRIC CANCER PATIENTS?

H. J. Kim¹², N. Kim¹, D. H. Lee¹

¹Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, ²Department of Internal Medicine, Myongji Hospital, Goyang, Republic of Korea

Contact E-mail Address: nayoungkim49@empas.com

Introduction: A large-scale study was performed to identify the risk factors for developing synchronous and metachronous colorectal cancer (CRC) in gastric cancer (GC) patients including microsatellite instability (MSI) and p53 overexpression.

Aims & Methods: A total 1041 GC patients who underwent endoscopic resection or surgery and who underwent colonoscopy simultaneously or during the surveillance of GC were consecutively included.

Results: Of the 1041 patients, CRCs were detected in 67 (6.4%) patients with GC. Forty six (4.4%) had synchronous CRC and 21 (2.0%) had metachronous CRC. Univariate analysis indicated that age ≥55 (P <0.001), male (P <0.001) and p53 overexpression (P = 0.040) had a higher incidence of CRC. However, body mass index, smoking, tumor location, tumor multiplicity, tumor histology, TNM stage and MSI were not significantly associated with the incidence of CRC. Age ≥55 (OR: 4.143; 95% CI: 1.863-9.213; P <0.001) and male (OR: 2.951; 95% CI: 1.323-6.583; P = 0.008) were the risk factors of CRC in GC patients by multivariate analysis.

Conclusion: GC patients who are 55 years and older or male are recommended to receive colonoscopy to detect CRC. MSI and p53 overexpression were not useful molecular markers for prediction of CRC in GC.

Disclosure of Interest: None declared

P0520 CLINICAL OUTCOME OF DOUBLET AND TRIPLET NEOADJUVANT CHEMOTHERAPY FOR MARGINALLY AND POTENTIALLY RESECTABLE GASTRIC CANCER. RETROSPECTIVE SINGLE CENTER CASE CONTROL STUDY

H. S. Moon¹, J. S. Kim¹, S. H. Kang¹, J. K. Sung¹, H. Y. Jeong¹

¹Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea

Contact E-mail Address: mhs1357@cnuh.co.kr

Introduction: Gastric cancer is the fourth most common malignancy in the world, and the second leading cause of cancer-related deaths and the highest mortality rates are reported in East Asia. Early detection and surgery are currently considered the mainstay of treatment, and approximately half of gastric cancer patients can be treated by curative surgical or endoscopic resection. However, the rate of recurrence and metastasis following radical resection remains disappointingly high. Thus, improving the rates of survival and cure is a critical goal. Theoretically the administration of the neoadjuvant chemotherapy (NAC) appears to have potential benefits for locally advanced gastric cancer, while its survival gain and surgical benefit remains controversial.

Aims & Methods: The aim of this study was to evaluate the effectiveness of NAC in treatment of marginally and potentially resectable gastric cancer and find out the associated factor of resistance to NAC. We retrospective reviewed the patient medical record. This study enrolled 179 patients who underwent NAC followed by surgery (n=41) or surgery only (n=138) for treatment of stage IIIa or IIIb locally advanced gastric cancer. For sampling, we applied a random sample extraction method. We categorized the NAC group and the Surgery only group according to gender and age, then we applied a serial number to each category. We used two chemo-regemen FOLFOX (n=28) and DCF (n=13). The basal characteristics and clinical outcome were compared between two groups. NAC related objective response, safety and toxicity were also analyzed.

Results: The basal characteristics including mean age and sex was not significant difference between two groups. Initial stage was significantly high (P=0.001) in NAC followed by surgery (3.12 0.56) than surgery only group (2.57 0.54). After NAC, the tumor down-stage rate was 58.5% (24/41). Both tumor size and differentiation were predictive factor of resistance to NAC. But overall survival (P=0.518), disease free survival (P=0.621) and recurrence rate (P=0.142) were not statistically difference between two groups. In subgroup analysis we compared clinical outcome between doublet (n=28) and triplet (n=13) NAC group. As a result, age, sex, tumor down stage rate and recurrence were similar between two groups. But drug toxicity (P=0.019) and initial stage (P=0.010) were significant higher in triplet NAC than doublet NAC group.

Conclusion: Compared with surgery only versus NAC followed by surgery was not associated with a survival gain or lower recurrence rate. However, Down of N stage is significantly improved statistically. In our data, tumor size and differentiation was the important clinical predictor. Therefore NAC may be benefit for selective treatment option and assessing individual prognosis.

Disclosure of Interest: None declared

P0521 FOLLOW-UP RESULT OF ENDOSCOPIC TREATMENT FOR GASTRIC ADENOMA

H. S. Moon¹, J. S. Kim¹, S. H. Kang¹, J. K. Sung¹, H. Y. Jeong¹

¹Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea

Contact E-mail Address: mhs1357@cnuh.co.kr

Introduction: Gastric adenoma(GA) is well known for premalignant lesion. Endoscopic treatment has been widely conducted for the treatment of gastric adenoma. However, the risk factors related to recurrence of adenoma and occurrence of adenocarcinoma after endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) for gastric adenoma have not been reported so much.

Aims & Methods: The aim of this study was to evaluate these factors. We reviewed medical records of total 667 lesions from 641 patients who underwent EMR/ESD for gastric adenoma from January, 2007 to December, 2013 at Chungnam National University Hospital. For all subjects, the data collected included sex, age, site of lesion, morphology, treatment method, severity of atrophy, intestinal metaplasia, resection margin and degree of dysplasia.

Results: The median follow up period was 29th month (range, 12-81 months). There were 98 recurrence of adenoma (14.7%) and 31 occurrence of adenocarcinoma (4.6%). The risk factors related to the recurrence of gastric adenoma were male (p=0.024), intestinal metaplasia (p=0.004) and incomplete resection margin (p=0.004). The risk factors related to the occurrence of gastric adenocarcinoma were male (p=0.015) and High grade dysplasia (p=0.019).

Conclusion: After EMR/ESD for gastric adenoma, the recurrence of gastric adenoma was associated with sex, intestinal metaplasia and resection margin, and the occurrence of adenocarcinoma was associated with sex and grade of dysplasia.

Disclosure of Interest: None declared

P0522 HOW TO MANAGE SUPERFICIAL NON-AMPULLARY DUODENAL TUMORS

H. Tomida¹, Y. Yamamoto², J. Fujisaki², M. Igarashi²

¹Division of Gastroenterology, Ehime Prefectural Central Hospital, Ehime, ²Division of Gastroenterology, Cancer Institute Hospital, Tokyo, Japan

Contact E-mail Address: hideomi.tomida.epch@hotmail.com

Introduction: As a minimally invasive therapy, endoscopic resection (ER) and laparoscopy endoscopy cooperative surgery (LECS) of superficial non-ampullary duodenal tumors (SNADT) have been performed recently. However, the indication criteria have not been clearly determined yet. It is difficult to carry out ER safely because of the thin wall of the duodenum, so ER of SNADT includes serious complications such as perforation. Uedo et al. reported that the location of the lesions in distal side from Vater’s ampulla was associated with the occurrence of delayed perforation. At the cancer institute hospital, ER is done only for SNADT measuring ≧20mm, whose ulcer floor can be closed completely using endoclips. LECS is the treatment choice for SNADT not amenable to ER in terms of technical and/or oncological reasons.

Aims & Methods: The aim of this study was to examine the validity of the treatment based on analyzing the therapeutic outcome. At the cancer institute hospital, 74 patients with SNADT treated by ER and 14 patients by LECS between September 2006 and December 2014. The ER methods used to carry out en bloc resection were endoscopic mucosal resection (EMR: n=35) or endoscopic submucosal dissection (ESD: n=39). The procedure of LECS was to close the mucosal defect after ESD with seromuscular suturing by laparoscope. We analyzed the therapeutic outcome of ER and LECS for SNADTs according to the location of the lesions that is proximal or distal side of Vater’s ampulla.

Results: First, we analyzed the clinical outcomes of ER by comparing the EMR group and the ESD group. We treated 36 SNADTs located in the proximal side from Vater’s ampulla (PVA) (21 with EMR and 15 with ESD) and 38 SNADTs located in the distal side from Vater’s ampulla (DVA) (14 with ER and 24 with ESD). In the gross type, most frequent types were 0-IIa in EMR, 0-IIc in ESD. (p < 0.001) The median tumor sizes were 9.5mm in EMR and 13mm in ESD, so the lesion treated with ESD was significantly larger than that of EMR. (p < 0.024) In R0 resection (negative margins), EMR was 15 lesions located in PVA (71%) and 12 lesions located in DVA (86%), ESD was 14 lesions located in PVA (93%) and 22 lesions located in DVA (92%). ESD was significantly higher than EMR in each lesion. No complication was found in EMR. Intraoperative perforation occurred in 2 patients (5.3%) and delayed perforation occurred in 2patients (5.3%) in ESD. All of the lesions were located in DVA. The lesion recurrence was found in 1 patient only in EMR. The lesion was also located in DVA. Then, in LECS group, the lesions located PVA and DVA were 4 and 10 patients, respectively. The median tumor size was 23.5mm. All of the lesions were achieved R0 resection. In the treatment of SNADTs located in DVA, postsurgical infection occurred in 2 patients (20%). Although they were cured with conservative management, a long hospital stay was required.

Conclusion: ER and LECS of SNADT are ideal and less invasive treatments compared with open surgical resection. However, these treatments include serious complications such as perforation, residual tumor and infection, especially in patients with lesions located in DVA. In the case of the lesions located in DVA, we should consider that open surgical resection is one of the safe and reliable treatments. In contrast, ER and LECS should be considered for the treatment of the lesions located in PVA to avoid unnecessary surgery and preserve patient’s quality of life.

Disclosure of Interest: None declared

P0523 GASTRIC ADENOCARCINOMA OF THE FUNDIC GLAND TYPE (CHIEF CELL PREDOMINANT TYPE): A MULTICENTRE STUDY OF 70 CASES

H. Ueyama¹, A. Nagahara², K. Matsumoto¹, Y. Akazawa¹, H. Komori¹, T. Takeda¹, K. Matsumoto¹, M. Hojo¹, T. Yao³, S. Watanabe¹

¹Gastroenterology, Juntendo University School of Medicine, Bunkyo-Ku, ²Gastroenterology, Juntendo University Shizuoka Hospital, Shizuoka, ³Human Pathology, Juntendo University School of Medicine, Bunkyo-Ku, Japan

Contact E-mail Address: psyro@juntendo.ac.jp

Introduction: Gastric adenocarcinoma of the fundic gland type (chief cell predominant type, GA-FG-CCP) has recently been proposed as a new variant of gastric adenocarcinoma. In 2010 and 2014, we described the clinicopathological and endoscopic features of GA-FG-CCP (Ueyama H. Am. J. Surg. Pathol 2010, Ueyama H. Endoscopy 2014). We found that GA-FG-CCP is rare but has distinct clinicopathological features, especially in terms of tumour location, histological findings, phenotypic expression, and low-grade malignancy. However, the treatment strategies and long-term outcomes of GA-FG-CCP have not been thoroughly investigated by studies with large sample sizes.

Aims & Methods: The aim of this study was to collect a large number of GA-FG-CCP cases and perform a detailed analysis of the clinicopathological features of GA-FG-CCP. A total of 70 GA-FG-CCP cases were retrospectively collected from 25 institutions between January 2008 and December 2014.

Results: A total of 70 patients [65.4 y (range 41-81 y), 50 male, 20 female] with 70 lesions were treated as follows: ESD/EMR/surgery=48/11/11. A total of 88% of patients were negative for H. pylori infection. In regards to lesion location, 55 were detected in the upper stomach, 14 in the middle stomach, and 1 in the lower stomach. Macroscopically, 44 lesions had a protruded shape (SMT shape: 22, 0-IIa:18, 0-I:4), whereas 26 had a flat/depressed shape (IIb:7, IIc:19). The mean tumour size was 12.0 (2-85) mm. Histologically, there were 20 intramucosal cancers and 50 submucosal invasive cancers. The mean depth of the submucosal invasion was 476.7 (50-4000) µm. Lymphovascular invasion was observed in 4 cases (5.7%). Lymph node metastasis was only observed in one out of 11 patients who underwent surgery (9.1%, 1/11). Follow-up data were available for 38 cases, and during the follow-up period (median 28.7 (1-104) months), no local recurrence or metastasis was detected in any case. For 7 of the 38 patients with follow-up data, endoscopic resection was determined to be non-curative, and of those 7 patients, four did not undergo additional surgery. However, there was no local recurrence and metastasis at a median of 32 months (4-82) follow-up after endoscopic treatment.

Conclusion: The findings of high-grade atypism, lymphovascular invasion, and LN metastasis in some GA-FG-CCP cases indicate that GA-FG-CCP may alter the atypism and cell differentiation of the tumour during the course of tumour progression, resulting in the development of high-grade malignancy. However, endoscopic treatment appeared to be effective, because neither recurrence nor metastasis was detected in any case regardless of whether additional surgery was performed. Therefore, the prognosis of GA-FG-CCP may be better than those of more common gastric cancers. Moreover, GA-FG-CCP should be categorized as a gastric adenocarcinoma that occurs without H. pylori infection, because H. pylori infection was considered an accidental phenomenon in this case series. Further studies will be needed to elucidate the natural history and carcinogenesis of GA-FG-CCP.

Disclosure of Interest: None declared

P0524 OUTCOME OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY GASTRIC CANCER WITH SCARRING

H. Komori¹, H. Ueyama¹, K. Matsumoto¹, Y. Akazawa¹, T. Takeda¹, K. Matsumoto¹, M. Hojo¹, A. Nagahara², S. Watanabe¹

¹Gastroenterology, Juntendo Univ., Bunkyo-ku, ²Gastroenterology, Juntendo Univ. Shizuoka Hosp., Izunokuni-shi, Japan

Contact E-mail Address: hiroyukikomori219@gmail.com

Introduction: Recently, with the advent and widespread use of endoscopic submucosal dissection (ESD), en bloc resection of early gastrointestinal cancer has become possible irrespective of the location and diameter. However, the technical difficulty is greatly dependent on the condition of the lesion and the skill of the endoscopist; a lesion with scarring, in particular, is technically challenging. The Japanese Treatment Guidelines for Gastric Carcinoma suggests that presence or absence of scarring may become a decisive factor in curative resection and an important finding for judging whether expanded surgery might be required. In addition, some reports have indicated that it is difficult to determine if scarring is present before performing ESD. The clinical management, including diagnosis, of cases with scarring before ESD has not been well investigated.

Aims & Methods: This study aimed to investigate clinicopathological characteristics and clinical management of early gastric cancer with scarring. We analysed 315 lesions and 318 cases of early gastric cancer treated by ESD at our hospital between April 2009 and February 2015 (225 males and 93 females; mean age 69.7 y). According to the presence or absence of pathologically diagnosed scarring, the cases were divided into two groups for comparison: Group UL+, 28 lesions in 27 cases (18 males and 9 females; mean age 72 y); and Group UL-, 323 lesions in 291 cases (210 males and 81 females; mean age 71.7 y).

Results: Scarring was accurately diagnosed endoscopically before ESD in 13 of 28 cases (46%) in Group UL+. There was no significant difference between the two groups in the following parameters (Group UL+ vs. Group UL-): the location of the lesion (U/M/L), 11/13/4 vs. 141/147/35; the operation time, 89.3 min vs. 63.7 min; the tumor diameter, 17.9 mm vs. 15.7 mm; and the diameter of the resected specimen, 39.0 mm vs. 36.9 mm. Macroscopically, the depressed type was significantly more often observed in Group UL+ (flat and elevated type/depressed type = 11%/89% in Group UL+ and 45%/55% in Group UL-, P < 0.01). Histologically, the mixed type (differentiated and undifferentiated cancer) was observed significantly more often in Group UL+ (differentiated type/mixed type = 75%/25% in Group UL+ and 88%/12% in Group UL-, P < 0.05). Despite no significant difference in invasion depth, SM cancer tended to be observed more frequently in Group UL+ (M/SM = 71%/29% in Group UL+ and 86%/14% in Group UL-, P = 0.06). The curative resection rate was significantly lower in Group UL+ (57% in Group UL+ and 86% in Group UL-, P < 0.01).

Conclusion: This study elucidated that early gastric cancer with scarring has high malignant potential and aggressiveness. It is often difficult to diagnose depth of invasion before ESD in cases of early gastric cancer with scarring.

Disclosure of Interest: None declared

P0525 GIST OR NON-GIST, THAT IS THE QUESTION: BASKET-LIKE HYPERVASCULARIZATION IN DOPPLER ENDOSCOPIC ULTRASONOGRAPHY- A HIGHLY SPECIFIC CRITERION FOR THE DETECTION OF A GASTROINTESTINAL STROMAL TUMOR

H. Neye¹, K. Mönkemüller², R. Hiersemann³, S. Rickes³

¹Department of Gastroenterology and Diabetology, HELIOS Hospital Emil von Behring Berlin, Berlin, Germany, ²Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, United States, ³Department of Internal Medicine, HELIOS Börde Hospital, Oschersleben, Germany

Contact E-mail Address: holger.neye@helios-kliniken.de

Introduction: Endoscopic ultrasonography (EUS) is the most important imaging method for diagnosis of subepithelial lesions of the gastrointestinal tract. However, it still has limits in the differentiation between Gastrointestinal Stromal Tumors (GISTs) from other malignant and benign tumors (Non-GISTs). As a result of the development of effective oncological therapy there is a high need for an imaging method to the diagnosis and follow-up of GISTs. In recent years Doppler EUS has been proposed as a method to distinguish GISTs from Non-GISTs. Therefore we initiated a prospective study to evaluate Doppler EUS criteria for the detection of a GIST.

Aims & Methods: Thirty-one patients (19 women, 12 men) with subepithelial lesions (n=32) were prospectively investigated using the EUS platform Olympus GF-UCT140 (Olympus Europe, Hamburg, Germany) and HDI 5000 (Philips Ultrasound, Bothell, USA). All Doppler EUS examinations were performed by one operator unaware of the histological results. Defined ultrasound parameters were used to determine the Doppler EUS observations. All tumors were proven histologically. The exact Chi-square Test (Fisher’s Test) was used to find significant differences between GISTs and Non-GISTs. P-values of less than 0.05 were considered to be significant. The study was conducted following the Good Clinical Practice Guidelines and according to the guidelines of the Helsinki Declaration.

Results: See table 1. Basket-like hypervascularization in Doppler endoscopic ultrasonography is a highly specific criterion in the differentiation between Gastrointestinal Stromal Tumors from other malignant and benign tumors (Non-GISTs).

Table 1.

Results of Doppler EUS examinations.

Criteria	GIST present	GIST absent	Non-GIST present	Non-GIST absent	p-value
Vessels detected	10	0	14	8	0.035
Afferent vessel	9	1	7	15	0.006
Basket-like hypervascularization	9	1	4	18	0.0002

Significance level: p-value less than 0.05

Conclusion: The differentiation of GISTs from other malignant and benign subepithelial lesions is a major issue in the management of these tumors. With this prospective study, we have addressed the need to evaluate diagnostic criteria for Doppler EUS criteria. The results demonstrated a basket-like hypervascularization is a highly specific criterion in the detection of a GIST. In the future, the direct detection of vessels could be the most important advantage of Doppler EUS contrary to other imaging methods.

Disclosure of Interest: None declared

P0526 ENDOSCOPIC GASTRIC ATROPHY IS A PREDICTING FACTOR IN HISTOLOGIC DISCREPANCY BETWEEN FORCEPS BIOPSY AND ENDOSCOPIC RESECTION IN LOW GRADE DYSPLASIA

Y. I. Lee¹, J. C. Park¹, H. S. Chung¹, S. K. Shin¹, S. K. Lee¹, Y. C. Lee¹

¹Division of Gastroenterology & Internal medicine, Yonsei University College of Medicine, Seoul, Republic of Korea

Contact E-mail Address: lyi610@yuhs.ac

Introduction: Histologic discrepancy between specimens obtained by forceps biopsy and endoscopic resection (ER) often occurs in gastric adenomatous lesions. The purpose of this study was to investigate that gastric atrophy could be one of clinical diagnostic factor for predicting histologic discrepancy between forceps biopsy and ER.

Aims & Methods: This study involved 203 gastric low grade dysplasia (LGD) that were proven on the basis of forceps biopsy and checked serum pepsinogen I/II level. ER is composed of 17 endoscopic mucosal resection and 186 endoscopic submucosal dissection. The lesions were grouped according to the histologic discrepancies between forceps biopsy and ER; concordant or discordant. The definition of discordance is histologic upgrade from LGD of forceps biopsy to high-grade dysplasia (HGD) or differentiated adenocarcinoma of ER. Gastric atrophy was diagnosed when either a endoscopic atrophy was confined around the adenomatous lesion or both serum pepsinogen level I ≤ 70 and pepsinogen I/II ratio ≤ 3.0 was satisfied.

Results: Histologic discrepancy between forceps biopsy and ER in gastric adenoma was 11.8% (24/203). The histologic upgrade to HGD or differentiated adenocarcinoma accounted for 5.4% (11/203) and 6.4% (13/203), respectively. Atrophy around the lesion in endoscopy accounted for 49.7%(101/203) and satisfaction of both serum pepsinogen I ≤ 70 and pepsinogen I/II ratio ≤ 3.0 accounted for 44.3%(90/203). In univariate analysis, atrophy around the lesion, upper third located lesion, erythema of the lesion, and satisfaction of both pepsinogen I ≤ 70 and pepsinogen I/II ratio ≤ 3.0 was found to be statistically significant factors affecting histologic discrepancy. In multivariate analysis, atrophy around the lesion (odd ratio [OR], 3.106; 95% confidence interval [CI], 1.075-8.980; P=0.036), upper third located lesion(OR, 5.641; 95% CI, 1.35-23.567; p=0.018) were significant factors associated with histologic discrepancy.

Abstract number: P0526 Table 1.

Histologic discrepancy between specimens obtained by forceps biopsy and endoscopic resection.

Variables			Univariate analysis	Multivariate analysis
	Condordant(n=179), n(%)	Discordant(n=24), n(%)	P value	P value	odds ratio (95% CI)
Atrophy around the lesion			0.012	0.036	3.106 (1.075-8.980)
Yes	83 (46.4)	18 (75.0)
No	96 (53.6)	6 (25.0)
PGI ≤ 70 and Ratio ≤ 3.0	74 (41.3)	16 (66.7)	0.023	0.129	2.082 (0.807-5.370)
Lesion type, n(%)			0.837	0.511	2.142 (0.221-20.792)
Depressed	6 (3.4)	1 (4.2)
Elevated/flat	173 (96.6)	239 (95.8)
Location			0.003	0.018	5.641 (1.350-23.567)
Non-upper	172 (96.1)	19 (79.2)
Upper	7 (3.9)	5 (20.8)
Size (mm)			0.259	0.540
≤10	80 (51.0)	9 (37.5)	Reference
>10 and 20≤	56 (35.7)	8 (33.3)	0.644	0.579	0.720 (0.226-2.296)
>20 and 30≤	17 (10.8)	6 (25.0)	0.053	0.569	1.904 (0.502-7.220)
>30	4 (2.5)	1 (4.2)	0.496	0.916	1.267 (0.102-15.806)
		zx
Ulcer	12 (6.7)	2 (8.3)	0.674	0.790	1.287 (0.201-8.249)

Conclusion: We should consider histologic discrepancy and tentative endoscopic resection for gastric LGD that is located upper third or accompanying atrophy around the lesion.

Disclosure of Interest: None declared

P0527 THE ROLE OF FOLLOW-UP ENDOSCOPY AND COMPUTED TOMOGRAPHY SCAN AFTER ENDOSCOPIC OR SURGICAL TREATMENT OF EARLY GASTRIC CANCER: A PRELIMINARY REPORT

I. S. Jung¹, C. M. Shin¹, Y. S. Park¹, S. J. Park¹, H. Yoon¹, N. Kim¹, D. H. Lee¹

¹Internal Medicine, Seoul National University Bundang Hospital, Seoungnam-si, Republic of Korea

Contact E-mail Address: scm6md@gmail.com

Introduction: Clinical outcome of early gastric cancer (EGC) is excellent, attributable to the progress in diagnostic and therapeutic methods. However, there is no relevant guideline for surveillance endoscopy and/or computed tomography (CT) scan, especailly for EGC.

Aims & Methods: The aim of this study was to investigate the role of regular endoscopy and CT scan surveillance after treatment of EGC. A total of 603 patients with EGC treated either by endoscopic [endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD)] or surgical treatment (gastrectomy with lymph node dissection) between January 2007 and December 2009 were retrospectively reviewed. All of the gastric lesions were completely resected and all of them had one or more endoscopy and CT scan examination during the follow-up.

Results: In the gastrectomy group (n = 492; mean follow-up, 46.1 months), 10 patients revealed tumor recurrence during the follow-up, including 3 cases with metachronous gastric adenoma, 1 with anastomosis site cancer recurrence, 1 with regional lymph node metastasis, and 5 with distant metastasis. All metachronous gastric adenomas were detected by endoscopy with biopsy. Six cases (5 distant metastases and 1 regional lymph node metastasis) were diagnosed by abdominal CT; the anastomosis site recurrence case was detected by both CT and endoscopy; all of these 7 cases were sm cancers and 2 of them had regional lymph node metastasis in the initial surgical pathology. In EMR/ESD group (n = 111; mean follow-up 51.3 months), 3 revealed metachronous gastric adenocarcinoma during the follow-up, all of which were deteced by endoscopy with biopsy; 2 of them also showed tumor recurrence in abdominal CT scan. All of these 3 cases meet the absolute criteria of ESD (< 2cm in size, m cancer, differentiated pathology) according to the initial resection specimen.

Conclusion: According to our preliminary report, regular follow-up of both endoscopy and CT scan is recommended after the surgery in the EGC patients. Especially, CT scan seems to be more valuable in case of sm cancers and/or lymph node metastasis. After endoscopic resection of EGC, all the recurrence could be detected by endoscopy with biospy, so CT scan might have a limited role for the surveillance of EGC after endoscopic resection of EGCs which meet the absolute criteria. However, further study is warranted in this issue.

Disclosure of Interest: None declared

P0528 ASSOCIATED FACTORS THAT LEAD TO RESIDUAL TUMOR IN PATIENTS WHO UNDERWENT ADDITIONAL GASTRECTOMY AFTER INCOMPLETE ENDOSCOPIC RESECTION FOR EARLY GASTRIC CANCER IN KOREA

J. J. Hwang¹, D. H. Lee¹, H. Yoon¹, C. M. Shin¹, Y. S. Park¹, N. Kim¹

¹Department of Internal medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea

Contact E-mail Address: frontierassa@hanmail.net

Introduction: The aim of this study was to evaluate the clinicopathological characteristics and factors that lead to residual tumors in patients who underwent additional gastrectomy for incomplete endoscopic resection in Korea.

Aims & Methods: Between 2003 and 2013, the medical records of patients underwent additional gastrectomy after incomplete ER were retrospectively reviewed. Those diagnosed with the presence of histologic residual tumor in specimens obtained by gastrectomy were assigned to the residual tumor (RT) group (n = 47); those diagnosed with the absence of histologic residual tumor in specimens obtained by gastrectomy were assigned to the non-residual tumor (NRT) group (n = 33). We analyzed comparison of the clinicopathologic characteristics of RT and NRT group, clinical factors influencing the presence of residual tumor, pathologic discrepancies between ER and additional gastrectomy, relationship between positive margins, depth of invasion with residual tumors and lymph node metastasis, cases of lymph node metastasis.

Results: The frequency of additional gastrectomy due to incomplete resection after ER for EGC was 8.7% (80/911), and 58.7% (47/80) of those patients had residual tumors. The rates of H. pylori infection, mixed macroscopic finding, tumor size over 2cm, endoscopic piecemeal resection, submucosal invasion, both (lateral and vertical) margin involvement were significantly higher in the RT group than in the NRT group (p < 0.05). In the multivariate analysis, endoscopic piecemeal resection (Odds ratio [OR]: 5.02, 95% confidence interval [CI]: 3.78-6.24), H. pylori infection (OR: 1.45, 95% CI: 0.98-1.92), large tumor size (> 2cm, OR: 2.96, 95% CI: 2.37-3.55), and both (lateral and vertical) marginal involvement (OR: 4.96, 95% CI: 4.13-5.79) were independent factors, predictive of the presence of residual tumor in additional gastrectomy after incomplete resection ER for early gastric cancer (p < 0.05)

Conclusion: Before ER, endoscopic examination along with EUS and MDCT should be used to accurately determine the GC invasion depth and the presence of LN metastasis. During ER, surgeons should attempt to perform en bloc resection when performing ER and attempt to resect the mucous membrane with adequate safety margins to prevent tumor invasion into the lateral and vertical margins. After ER, effort should be made to ensure timely and accurate decisions about whether additional gastrectomy is needed using the pathological findings of the resected tissues, to ensure that there is no delay in surgery.

Disclosure of Interest: None declared

P0529 THE RISK FACTORS OF LYMPH NODE METASTASIS FOR MIXED ADENOCARCINOMA IN EARLY GASTRIC CANCER

J. P. Han¹, S. J. Hong¹, H. K. Kim², B. M. Ko¹, G. S. Cho³

¹Digestive Disease Center, Department of Internal Medicine, ²Department of Pathology, ³Department of Surgery, Soon Chun Hyang University School of Medicine, Bucheon, Republic of Korea

Contact E-mail Address: rock5014@schmc.ac.kr

Introduction: Endoscopic submucosal dissection (ESD) is widely accepted as treatment for early gastric cancer (EGC) due to its minimal invasiveness, and better quality of life associated with preserving gastrointestinal function. However, there is no consensus on ESD for mixed adenocarcinoma. This study aimed to evaluated the risk factor of lymph node (LN) metastasis and validate the ESD criteria as a curative resection for mixed adenocarcinoma in EGC.

Aims & Methods: Of 692 EGC patients who had undergone gastrectomy with LN dissection between 2001 and 2013, 60 were diagnosed as mixed adenocarcinoma after histological evaluation in surgical specimens and were analyzed retrospectively.

Results: LN metastasis was detected in 13 (21.7%) of 60 mixed adenocarcinoma. There were no significant differences in the gender ratio of male to female (74.5%: 25.5% in LNN group vs. 53.8%: 46.2% in LNP group, p=0.181) and age (58.9 ± 11.7 in LNN group vs. 57.8 ± 12.3 in LNP group, years, p=0.770) between LN negative group (LNN group) and LN positive group (LNP group). The histological evaluation showed that the size of EGC was significant larger in LNP group than in LNN group (26.1 ± 10.0 in LNN group vs. 36.1 ± 8.7 in LNP group, mm, p=0.002). The rates of LN metastasis were different according to the tumor size (35.1% in tumor > 20 mm vs. 0% in tumor ≤ 20 mm, p=0.003) and the presence of submucosal invasion (32.5% in submucosal cancer vs. 0% in mucosal cancer, p=0.006). None of mucosal cancer ≤ 20 mm and 48.1% of submucosal cancers > 20 mm in size had LN metastasis.

Conclusion: The risk of LN metastasis is high in mixed adenocarcinoma with more than 20 mm in size and submucosal invasion. Therefore, additional surgical treatment should be recommended in mixed adenocarcinoma with high risk factors even after complete resection by endoscopic procedures.

Disclosure of Interest: None declared

P0530 ENDOSCOPIC ESTIMATION OF TUMOR EXTENT USING LONG AND SHORT DIAMETER IN EARLY GASTRIC CANCER

J. H. Kim¹, S. R. Jee¹, S. H. Lee¹, J. W. Hwang¹, S. Y. Seol¹

¹Gastroenterology, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea, Busan, Republic of Korea

Contact E-mail Address: zep2000@inje.ac.kr

Introduction: Exact measurement of lesion extent in gastric epithelial neoplasm is critical for deciding treatment strategy. Although maximal diameter of the lesion is usually indicated as an actual tumor burden in early gastric cancer (EGC), certification of its validity has not been determined.

Aims & Methods: The purpose of the study was to evaluate the validity of lesion diameter and calculated lesion area for predicting actual tumor burden. We also aimed to assess the clinicopathologic factors related to discrepancy between PTE and ATE. We prospectively enrolled 302 EGCs from 290 consecutive patients who underwent endoscopic submucosal dissection as a primary treatment modality and in whom histologic results showed complete resection. Biopsy forcep method was used to measure the pre-sectional long and short diameter of the lesion. Predictive tumor extent (PTE) was calculated using pre-resectional long and short diameter (long diameter x short diameter x 0.5, mm²). Actual tumor extent (ATE) was measured as mm² unit using histologically constructed report and ImageJ Program (NIH Image version 1.55). Correlation between pre-resectional long/short diameter, PTE and ATE were analyzed. The well-estimated group was defined as lesion with ratio of PTE/ATE from 0.7-1.3. The underestimated and overestimated groups were defined as lesions with ratios of PTE/ATE less than 0.7 and more than 1.3, respectively.

Results: Correlation coefficient between pre-resectional long diameter and ATE, and PTE and ATE were 0.67 (P < 0.01) and 0.69 (P < 0.01), respectively. There was no significant different between PTE and ATE (167.00 ± 13.08 mm² vs 166.12 ± 10.89 mm²). Number of well-estimated, underestimated and overestimated groups were 89 (29.5%), 94 (31.1%) and 119 (39.4%), respectively. Elevated macroscopic morphology and absence of adenomatous component were significant independent factors for well-estimation. Depressed or flat macroscopic morphology, presence of adenomatous component and histologic lesion size less than 1 cm were significant independent factors for overestimation. Histologic lesion size was the only independent factor related to underestimation

Abstract number: P0530

Factors	Well-estimation		Overestimation		Underestimation
OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value
Size		0.177		<0.001		<0.001
≤ 1cm			10.00(4.52-2.19)		reference
>3cm			Reference		15.66(6.29-38.46)
Marcoscopic type		0.006				0.201
Elevated	2.37(1.28-4.38)		Reference	0.026
Flat/depressed	reference		2.75(1.733-5.85)
Presence of adenomatous component		0.014		0.014		0.099
Absence	reference		Reference
Presence	2.67(1.22-5.87)		2.67(1.22-5.86)

Conclusion: Endoscopically measured tumor extent using long and short diameter can be a useful indicator for actual tumor extent in EGC. Marcoscopic morphology, presence of adenomatous component and histologic lesion size were the significant clinicopathlogic factors related to accurate endoscopic estimation of actual tumor extent.

Disclosure of Interest: None declared

P0531 THE USEFULNESS OF MAGNIFYING ENDOSCOPY WITH NARROW-BAND IMAGING FOR PREDICTION ON PRE- AND POST-RESECTIONAL HISTOLOGIC DISCREPANCIES IN GASTRIC LOW-GRADE DYSPLASIA DIAGNOSED BY ENDOSCOPIC BIOPSY

J. W. Hwang¹, J. H. Kim¹, S. R. Jee¹, S. H. Lee¹, S. Y. Seol¹

¹Departments of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea

Contact E-mail Address: moneyhwang79@gmail.com

Introduction: MENBI categorical classification systems were suggested by the Japanese enscopitsts. Vessel plus surface (VS) classification, suggested by Yao et al, was known as useful tool for differential diagnosis between gastric adenoma with LGD and EGC, but few reports have evaluated about the feasibility of this classification system for predicting histologic discrepancy between pre-treatment endoscopic biopsy and post-treatment specimens, especially in other place than Japan.

Aims & Methods: The aim of this study was to evaluate the validity of the parameters of conventional endoscopic and magnifying endoscopy with narrow-band imaging (MENBI) for the prediction of histologic discrepancies between pre- and post-resectional histology in cases of gastric adenoma with low-grade dysplasia (LGD) that were diagnosed based on endoscopically biopsied specimens. The medical records of 149 consecutive patients with gastric LGD and 160 total lesions that were diagnosed based on an endoscopic forceps biopsy were retrospectively reviewed. These patients all underwent a MENBI examination. The incidence of histologic discrepancies and histologic heterogeneity were then analyzed. The relationship between conventional endoscopic/MENBI parameters and the presence of histologic discrepancies were also analyzed.

Results: Histologic discrepancie between the pre- and post-resectional histology were found in 49 cases (30.62%). Among those cases, the histology was upgraded in 47 cases, whereas the histology was downgraded in two cases. Older age, the presence of erythema, positive MENBI findings and the presence of discontinuous lesions were independent factors for the prediction of upgraded histologic discrepancies (p value = 0.046, 0.004, <0.001 and 0.038, respectively). Positive MENBI findings showed the highest predictive value, with a multivariate adjusted odds ratio of 19.812. Histologic heterogeneity in post-resectional specimens was found in 27.7% of cases with upgraded histologic discrepancies. Positive MENBI findings (p=0.008) and the presence of discontinuous lesions (p=0.031) were significant independent factors for the presence of histologic heterogeneity.

Conclusion: Endoscopic resection is recommended in cases of gastric adenoma with LGD that is diagnosed by forceps biopsy that demonstrate (1) surface erythema on conventional endoscopy or (2) a positive finding on the MENBI examination, irrespective of the lesion size. A careful histologic analysis for the presence of discontinuous lesions may be valuable for the detection of histologic heterogeneity.

Disclosure of Interest: None declared

P0532 POSTOPERATIVE NEUTROPHILS TO LYMPHOCYTE RATIO CHANGE IS STATISTICALLY ASSOCIATED WITH OVERALL AND DISEASE-FREE SURVIVAL IN PATIENTS WITH GASTRIC ADENOCARCINOMA

B. K. Son¹, J. Ha¹, S. W. Cho¹, S. B. Ahn¹, Y. J. Cho¹, S. H. Kim¹, Y. S. Park¹, K.-W. Min², D.-H. Kim³, E. K. Kim⁴

¹Department of Gastroenterology, Eulji Medical Center, Seoul, ²Department of Pathology, Hallym University Sacred Heart Hospital, Anyang, ³Department of Pathology, Kangbuk Samsung Hospital, ⁴Department of Pathology, Eulji Medical Center, Seoul, Republic of Korea

Contact E-mail Address: sbk1026@eulji.ac.kr

Introduction: A high preoperative neutrophil-to-lymphocyte ratio (NLR) has been reported to be a prognostic factor for patients with gastric cancer after treatment. However, the clinical implication of postoperative NLR change remains unclear.

Aims & Methods: Three hundred forty-seven patients diagnosed as gastric adenocarcinoma between 2003 and 2014 from two institution (Eulji and hallym hospital) were included. Each subject underwent endoscopic submucosal dissection or gastrectomy. The NLR was recorded within 1 months before and 8 month after surgical procedure. Baseline characteristics, overall survival (OS) and disease-free survival (DFS) were compared according to preoperative NLR and/or postoperative NLR change.

Results: Compared with preoperative NLR, postoperative NLR decreased in 205 patients and increased in 141 patients after surgical treatment. Receiver operating characteristic (ROC) curve exhibited good discriminatory power considering the overall survival for postoperative NLR than preoperative NLR (area under the ROC = 0.744 and 0.54), respectively. Comparing to preoperative NLR, increased postoperative NLR was significantly associated with poor OS and DFS (p < 0.001). The 1, 3, 5 years OS was 92.7%, 83.4%, 80.5% for NLR decreased group, and 83.8%, 71.8%, 63.4% for NLR increased group respectively; the corresponding RFS was 92.7%, 85.9%, 33.8% and 83.8%, 69.7%, 63.4% respectively. The survival of patients with lower or higher preoperative NLR can be distinguished more accurate by postoperative NLR change. Multivariate analysis showed that postoperative increased NLR change was an independent prognostic factor for both OS (P < 0.001, HR = 2.552, 95% CI 1.744–3.734) and RFS (P < 0.001, HR = 2.442, 95% CI 1.609–3.707).

Conclusion: After operation, increased NLR change was an independent prognostic factor for gastric adenocarcinoma undergoing surgical procedure, comparing with decreased NLR change.

Disclosure of Interest: None declared

P0533 ANTITUMOR EFFICACY OF GLV-1H153 FOR PERITONEALLY DISSEMINATED GASTRIC CANCER

K.-H. Jun¹

¹Surgery, St. Vincent's Hospital, Suwon, Republic of Korea

Contact E-mail Address: dkkwkh@catholic.ac.kr

Introduction: Novel therapies are necessary to improve outcomes for patients with peritoneally disseminated gastric cancer. Vaccinia virus has been shown to be an effective oncolytic agent, and genetic manipulations of this virus make it possible to monitor noninvasively therapeutic efficacy and potential toxicity.

Aims & Methods: We examined the therapeutic effects of genetically engineered vaccinia as an oncolytic agtent against peritoneally disseminated gastric cancer.

GLV-1h153 was modified from parental vaccinia virus GLV-1h68 to carry hNIS via homologous recombination. GLV-1h153 was tested against human gastric cancer cell line OCUM-2MD3 for replication via viral plaque assays. Viral cytotoxicity and tumore regression of treated OCUM-2MD3 tumor xenografts in nude mice was also determined. Tumor radiouptake in xenograft was assessed via 99mTc pertechnetate scintigraphy and 124I positron emission tomography.

Results: GLV-1h153 infected, replicated within, and killed OCUM-2MD3 cells efficiently. GFP expression conformed viral infection by 24 hours. In vivo, GLV-1h153 was safe and effective in a peritoneal cancer model that simulates clinical disease. A single injection of GLV-1h153 into peritoneal cancer model exhibited intratumoral luciferase activity peaking at days 5-7, with gradual resolution over 10 days. Intraperitoneal injection of GLV-1h153 facilitated imaging of virus replication in tumors via 99mTc pertechnatate scintigraphy and 124I PET.

Conclusion: These results demonstrate significant oncolytic efficacy by gentically GLV-1h153 virus for infecting and lysing peritoneally disseminated gastric cancer both in vitro and in vivo, and support its contined investigation in future clinical trials.

Disclosure of Interest: None declared

P0534 ROLE OF STRESS, DIETERY NITRITES AND NITROSO-COMPOUNDS IN TRASFORMATION OF GASTRIC ULCER INTO CANCER OF STOMACH: NITRERGIC AND ADRENERGIC MECHANISMS

O. Semyachkina-Glushkovskaya¹, E. Borisova², I. *Agranovich¹, K. Mohanad¹

¹Saratov State University, Saratov, Russian Federation, ²Institute of Electronics, Bulgarian Academy of Sciences, Sophya, Bulgaria

Contact E-mail Address: glushkovskaya@mail.ru

Introduction: Chronic ulcer of stomach is a main risk for gastric cancer. The mechanisms underlying transformation of gastric ulcer to cancer are not well established but there is much epidemiological data suggesting that stress and exogenous N-nitroso-compounds (NOCs) from diet play a major role in these pathological processes. In our previous studies we showed that chronic social stress causes ulcer formation that is associated with pathological changes in local mechanisms of microcirculatory regulation such as nitric oxide (NO) and adrenomediated vasorelaxation. In our clinical work we obtained the abnormal effect of adrenalin on gastric vessels (relaxation) and the hyperteactivity of NO-system in epithelium of stomach in patients with gastric cancer.

Aims & Methods: Here we studied the nitrergic and adrenergic mechanisms of cancerogenic effect of chronic stress (overpopulation, immobilization) and exogenous nitrites/NOCs in rats with gastric stress-related ulcer. The experiments were carried out on six groups of rats: 1) intact (n=12) and 2) stressed (n=23) rats without nitrites/NOCs administration; 3) intact (n=25) and 4) stressed (n=25) rats with daily administration of N-methylaniline (2g/kg of diet) in the feed with sodium nitrite in the drinking-water (1 g/L); 5) intact (n=20) and 6) stressed (n=25) rats with daily administration of N-methylaniline without sodium nitrite. In all groups we analyzed gastric blood flow by LSCI, expression of beta2-adrenoreceptors (B2-AR – a key factor of microcirculatory regulation) by immunohistochemistry and NO/beta-arrestin-1 (co-factors of B2-AR activation) level in epithelium of stomach using spectrophotometry and immunoassay.

Results: Chronic stress (overpopulation) during 5 months was accompanied by primarily erosions in 64% of rats (2d group - stress), 72% (6^th group – stress + NOCs) and 93% (4^th group – stress+ nitrites/NOCs). Additional daily stress (4h immobilization) during 1 month induced development of ulcers in stomach in all rats with stress-related injury of gastric mucosa that was more pronounced in 4^th group vs. 2d and 6^th groups. The gastric epithelial dysplasia as a sign of pre-cancer formation we found only in 4^th group of stressed rats (stress + nitrites/NOCs). In other groups we identified ulcer injures but not mutagenic changes in epithelium of stomach. In intact rats of 1,3,5 groups, gastric tissues were not changed. In all groups of stressed but not in intact rats we observed increase in the level of NO in gastric epithelium. Only stressed rats with gastric epithelial dysplasia demonstrated increase in gastric perfusion that was associated with overexpression of B2-AR, high level of beta-arrestin-1 and more higher level of NO in gastric epithelium that in other groups.

Conclusion: Combination of chronic stress and exogenous nitrites/NOCs are factors for transformation of stress-related gastric ulcer into cancer of stomach. The pathological mechanisms of microcirculatory regulation such as overexpression of B2-AR and the increase in production of co-factors of B2-AR activation – NO and beta-arrestin-1 play an important role in cancerogenic effect of stress and nitrites/NOCs in rats with gastric ulcer.

Research was supported by grant from Russian Ministry of Science and Education (GK-17.488.2014/K).

Disclosure of Interest: None declared

P0535 LONG NONCODING RNA MALAT1 PROMOTES AGGRESSIVE GASTRIC CANCER THROUGH MMP1 OVER-EXPRESSION AND TRANSCRIPTIONALLY ACTIVATED BY C-JUN

W. Jin¹

¹The First Affiliated Hospital of Nanjing Medical University, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China

Contact E-mail Address: zhouxiaoying0926@sina.cn

Introduction: Recently long non-coding RNAs (lncRNA) have emerged as new gene regulators and prognostic markers in several cancers including gastric cancer (GC). In this study, we investigated the contributions of the lncRNA MALAT1, a highly conserved long noncoding RNA, in GC and its posttranscriptional regulation.

Aims & Methods: We analyzed MALAT1 expression levels by qRT-PCR and in four GC cell lines compared with epithelial cells. Transient RNAi-mediated knockdown and pcDNA-mediated overexpression of MALAT1 was performed. Stable shRNA-mediated knockdown and lentiviral-mediated overexpression of MALAT1 was to study the role of MALAT1 on in vivo tumorigenicity and metastatic burden in the context of xenograft assays. Proteomic profiling was performed to decipher differential protein expression in cells with different MALAT1 expression levels. One of the differentially regulated proteins, MMP1 was subsequently validated and its function evaluated through xenograft assays.

Results: We found that MALAT1 expression was higher in human GC tissues where it was associated with reduced patients’ survival. MALAT1 silencing decreased GC cell proliferation and invasion and increased apoptosis. Mechanistic investigations showed that MALAT1 was transcriptionally activated by c-Jun and that it interacted with MMP1. MMP1 and MALAT1 had a positive relationship, both at expression level and in function. Direct interaction between the two was confirmed through RNA immunoprecipitation coupled with quantitative real time PCR. MMP1 was confirmed to be promoter of GC pathogenesis and as functionally similar to MALAT1 lncRNA.

Conclusion: We found that MALAT1 expression was higher in human GC tissues where it was associated with reduced patients’ survival. MALAT1 silencing decreased GC cell proliferation and invasion and increased apoptosis. Mechanistic investigations showed that MALAT1 was transcriptionally activated by c-Jun and that it interacted with MMP1. MMP1 and MALAT1 had a positive relationship, both at expression level and in function. Direct interaction between the two was confirmed through RNA immunoprecipitation coupled with quantitative real time PCR. MMP1 was confirmed to be promoter of GC pathogenesis and as functionally similar to MALAT1 lncRNA.

Disclosure of Interest: None declared

P0536 CLINICAL ROLE OF CIRCULATING MIR-223 AS NOVEL BIOMARKER IN EARLY DIAGNOSIS OF CANCER PATIENTS

X. Zhou¹

¹Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China

Contact E-mail Address: zhouxiaoying0926@sina.cn

Introduction: Current procedures for diagnosis and biomarker examination of cancers are invasive and non-specific. MicroRNAs (miRNAs) have become promising molecular markers for GC predication. However, there have been inconsistencies in the literature regarding the suitability of circulating miRNAs for early detection of cancers.

Aims & Methods: We performed a comprehensive meta-analysis to integrate an evaluation index for diagnostic accuracy of miR-223 in diagnosing cancer patients. Furthermore, we conducted an independent validation set of 50 gastric cancer patients and 50 healthy controls comparing miR-223 expression.

Results: A total of 11 studies met the criteria and included in this meta-analysis. We found that miR-223 yielded a pooled area under ROC curve (AUC) of 0.89 (sensitivity: 81%, specificity: 84%) in discriminating cancer from controls. In our validation analysis, plasma miR-223 levels in GC patients were significantly higher than that in healthy controls (p < 0.01). ROC curve analysis showed that AUC was 0.812 with sensitivity of 70% and specificity of 80%. Moreover, the expression trend of miR-223 in plasma samples was in accordance with that of tissue and cell samples.

Conclusion: In conclusion, current evidences suggest that plasma miR-223 could be a reliable and non-invasive biomarker for cancer diagnosis. Further large-scale prospective studies are necessary to validate their potential applicability in human cancer diagnosis.

Disclosure of Interest: None declared

P0537 IDENTIFICATION OF THE LONG NON-CODING RNA H19 IN PLASMA AS A NOVEL BIOMARKER FOR DIAGNOSIS OF GASTRIC CANCER

X. Zhou¹, G. Zhang¹

¹Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China

Contact E-mail Address: zhouxiaoying0926@sina.cn

Introduction: Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are regarded as useful tools for cancer detection, particularly for the early stage; however, little is known about their diagnostic impact on gastric cancer (GC).

Aims & Methods: We hypothesized that GC-related lncRNAs might release into the circulation during tumor initiation and could be utilized to detect and monitor GC. 8 lncRNAs which previously found to be differently expressed in GC were selected as candidate targets for subsequent circulating lncRNA assay. After validating in 20 pairs of tissues and plasma in training set, H19 was selected for further analysis in another 70 patients and 70 controls.

Results: Plasma level of H19 was significantly higher in GC patients compared with normal controls (p < 0.0001). By receiver operating characteristic curve (ROC) analysis, the area under the ROC curve (AUC) was 0.838; p < 0.001; sensitivity, 82.9%; specificity, 72.9%). Furthermore, H19 expression enabled the differentiation of early stage GC from controls with AUC of 0.877; sensitivity, 85.5%; specificity, 80.1%. Besides, plasma levels of H19 were significantly lower in postoperative samples than preoperative samples (p=0.001).

Conclusion: In conclusion, plasma H19 could serve as a potential biomarker for diagnosis of GC, in particular for early tumor screening.

Disclosure of Interest: None declared

P0538 THE INTERACTION BETWEEN MIR-141 AND LNCRNA-H19 IN REGULATING CELL PROLIFERATION AND MIGRATION IN GASTRIC CANCER

X. Zhou¹

¹Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China

Contact E-mail Address: zhouxiaoying0926@sina.cn

Introduction: Non-coding RNAs including miRNA and lncRNA had been reported to regulate gene expression and were both related to cancer progression. MicroRNA-141 (miR-141) has been reported to play a role in the epithelial to mesenchymal transition (EMT) process and H19 has also been demonstrated to promote malignancy in various cancers.

Aims & Methods: We aimed to determine the correlation between miR-141 and H19 and their roles in gastric cancer in this study. H19 and miR-141 expression were detected by qRT-PCR. By bioinformatic analysis and luciferase assay, we examined the correlation between H19 and miR-141.

Results: H19 expression was found to be inversely correlated to miR-141 expression in gastric cancer cells and tissues. H19 promotes malignancy including proliferation and invasion whereas miR-141 suppresses malignancy in human cancer cells. MiR-141 binds to H19 in a sequence specific manner, and suppresses H19 expression and functions including proliferation and invasion. MiR-141 could also regulate H19 target genes and miR-141 inhibitor restores H19 siRNA function, while H19 regulates miR-141 target gene ZEB1.

Conclusion: These results were the first to demonstrate that H19 and miR-141 could compete with each other and affect their target genes in gastric cancer, which provide important clues for understanding the key roles of lncRNA-miRNA functional network in cancer.

Disclosure of Interest: None declared

P0539 LONG-TERM COHORT STUDY ON THE RECURRENCE OF BLEEDING AND PROGNOSIS OF PATIENTS HOSPITALIZED FOR ACUTE ESOPHAGEAL VARICEAL BLEEDING

H. Cho¹, N. Nagata¹, T. Sakurai¹, S. Moriyasu¹, K. Watanabe¹, K. Imbe¹, S. Mikami¹, Y. Nozaki¹, C. Yokoi¹, Y. Kojima¹, M. Kobayakawa¹, M. Yanase¹, J. Akiyama¹

¹Gastroenterology and Hepatology, National Center for Global Health and Medicine, Shinjyuku-ku, Tokyo, Japan

Contact E-mail Address: cho_hourin@yahoo.co.jp

Introduction: A limited number of studies have reported on the long-term recurrence and mortality in acute esophageal variceal bleeding. This study aimed to elucidate the rates of re-bleeding and mortality and the associated risk factors in patients with esophageal variceal bleeding.

Aims & Methods: A cohort of 174 patients emergently hospitalized for esophageal variceal bleeding was analyzed. All patients underwent endoscopic variceal ligation (EVL) within 12 h of onset. The co-morbidities, drugs use, initial vital sign, laboratory data, follow-up endoscopy were assessed. The Kaplan-Meier method was used to estimate the cumulative re-bleeding and mortality. The Cox proportional hazards model was used to estimate hazard ratio (HR) for mortality. In the re-bleeding risk analysis, we calculated the subdistribution hazard ratio (SHR), treating death without re-bleeding as a competing risk.

Results: Re-bleeding was identified in 49 patients with a mean follow-up of 18 months. The cumulative re-bleeding rate at 1 month, 1 and 5 years was 10.2%, 30.0% and 51.0%, respectively. In univariate analysis, re-bleeding was associated with Child-Pugh class C (p=0.03), alcoholic liver cirrhosis (p=0.001), none follow-up endoscopy (p < 0.001), and none follow-up EVL (p=0.004). Multivariate analysis revealed alcoholic liver cirrhosis (SHR, 3.03; p=0.003) and none follow-up endoscopy (SHR, 3.13; p=0.001) as independent risk factors for re-bleeding. During the mean follow-up of 22 months, 69 patients died, 17 due to bleeding. The cumulative mortality rate at 1 month, 1 and 5 years was 12.2%, 26.6% and 63.0%, respectively. In univariate analysis, mortality was associated with age ≥65 years (p=0.009), Child-Pugh class C (p < 0.001), coexistence of hepatocellular carcinoma (HCC) (p=0.013), none follow-up of endoscopy (p < 0.001), and none follow-up of EVL (p=0.001). Multivariate analysis revealed Child-Pugh class C (HR, 2.91; p < 0.001), coexistence of HCC (HR, 1.92; p=0.013), none follow-up endoscopy (HR, 25.0; p < 0.001) as independent risk factors of mortality.

Conclusion: This study demonstrated more than 50% cumulative re-bleeding and mortality in the 5-year period after hospitalization for acute esophageal bleeding. Alcoholic liver cirrhosis and none follow-up endoscopy increased risk of re-bleeding, whereas Child-Pugh class C, coexistence of HCC, and none follow-up of endoscopy increased risk of mortality.

Disclosure of Interest: None declared

P0540 ENDOSCOPIC VISIBLE LIGHT SPECTROSCOPY IN PATIENTS WITH CHRONIC GASTROINTESTINAL ISCHEMIA AND HEALTHY CONTROLS

J. Harki¹, L. J. van Dijk¹, D. van Noord¹, E. T. Tjwa¹, E. J. Kuipers¹², M. J. Bruno¹

¹Gastroenterology and Hepatology, ²Internal Medicine, Erasmus MC University Medical Centre, Rotterdam, Netherlands

Contact E-mail Address: j.harki@erasmusmc.nl

Introduction: Chronic gastrointestinal ischemia (CGI) is the result of decreased mucosal perfusion, in most cases due to atherosclerotic stenosis of the supplying mesenteric arteries. Visible light spectroscopy (VLS) enables direct measurement of mucosal oxygenation saturations during upper endoscopy (1,2). Limited data are available on VLS measurements in patients with CGI compared to a healthy population (2). We aimed to investigate the difference in mucosal oxygen saturation determined by VLS between patients with clinical suspicion of CGI and healthy controls.

Aims & Methods: Consecutive patients with a clinical suspicion of CGI referred to a tertiary care center were prospectively included between September 2014 and April 2015. All patients received the standard work-up for CGI, consisting of assessment of medical history and symptoms, radiological imaging of the gastrointestinal arteries, and VLS measurements. The results were discussed in a multidisciplinary expert panel leading to a consensus diagnosis, which was monitored during follow-up. Healthy, non-smoking volunteers with patent gastrointestinal arteries and unremarkable medical history were after informed consent included as controls. VLS measurements were performed during gastroscopy at three specific locations: gastric antrum, duodenal bulb, and descending duodenum.

Results: We performed 279 VLS measurements in 19 patients with clinical suspicion of CGI (mean age 59.9 (IQR 44.2-66.7) years, 53% male) and 12 controls (33.7 (IQR 29.0-41.2) years, 42% male). CGI was diagnosed in ten (53%) patients and excluded in nine (47%) patients. There was a significant difference in VLS measurements in all locations between patient with CGI and no CGI (antrum 57% (IQR 53-60) vs. 61% (IQR 60-62), p=0.04; duodenal bulb (51% (IQR 47-54) vs. 58% (IQR 54-59), p=0.004; descending duodenum 50% (IQR 45-52) vs. 54% (IQR 52-58), p=0.008, respectively). VLS measurements were significantly lower in the gastric and duodenal bulb of patients with CGI compared to healthy controls (57% (IQR 53-60) vs. 61% (IQR 59-65), p=0.04 and 51% (IQR 47-54) vs. 55% (IQR 53-62), p=0.007, respectively).

Conclusion: Patients with CGI have significantly lower mucosal oxygen saturation levels than patients without CGI as well as healthy controls. VLS can adequately assess mucosal oxygenation. This study confirms the diagnostic value of VLS in distinguishing patients with CGI from patients without CGI and healthy subjects.

Disclosure of Interest: None declared

P0541 KAPOSI SARCOMA INVOLVING THE GASTROINTESTINAL TRACT

M. Gravito-Soares¹, E. Gravito-Soares¹, S. Lopes¹, L. Tomé¹, C. Sofia¹

¹Gastroenterology, Centro Hospitalar e Universitário Coimbra, Coimbra, Portugal

Contact E-mail Address: ms18498@gmail.com

Introduction: Kaposi sarcoma (KS) is a low-grade vascular tumour associated with type-8 human herpes virus infection (HHV-8). In pre-antiretroviral therapy era, gastrointestinal involvement was frequent, up to 40% at the diagnosis and up to 80% at the autopsy. In our days, gastrointestinal affection is uncommon.

Objective: Characterization of gastrointestinal involvement by KS.

Aims & Methods: Of 38 biopsies with histologic KS diagnosis, between 2000-2014, it was selected KS cases with gastrointestinal affection. The analysed variables were clinic, analytic, etiologic, endoscopic features, histologic, therapeutic, therapeutic response and mortality.

Results: Nine cases of gastrointestinal KS was identified in fifteen years of study and 25.0% of them happened in 2014. All patients were males, black (22.2%) with diagnosis mean age of 50.4 ± 13.4 years old. The most common type was epidemic/HIV-associated (88.9%), followed by iatrogenic (11.1%). The first type was associated with HIV (100.0%), sexual promiscuity (62.5%), mean CD4+ 136.6 ± 233.1 cells/mm³ and CDCC3 stage (87.5%). Oral cavity and cutaneous involvement were present in 77.8%, affecting lower limbs in 85.7% and thorax in 71.4%. The main gastrointestinal clinic was dysphagia/odynophagia (44.4%) and nausea/vomiting (33.3%). Esophagogastroduodenoscopy was performed in all patients, with stomach involvement in all cases, mainly in the body (77.8%), followed by duodenum (44.4%) and oesophagus (33.3%). Endoscopy classic features identified were isolated or forming conglomerates violet papules/nodules. Colonoscopy was done in 33.3% of patients with ileocolic lesions in 33.3%. Histopathological features were fusocelular proliferation, storiform pattern, intra-cytoplasmic hyaline globules and vascular slits. Imunohistochemical profile showed CD34 and HHV-8 positivity. Doxorubicin treatment was applied in 66.7% patients (7.8 ± 1.9 cycles). Mortality occurred in 22.2% and was not directly KS-related.

Conclusion: KS is a rare tumour, with male predominance, HIV-associated and CD4+<200cells/mm³. Gastrointestinal involvement was more common in stomach body, with good response to chemotherapy. Diagnosis and treatment should be considered in symptomatic patients.

Disclosure of Interest: None declared

MONDAY, OCTOBER 26, 2015   09:00-17:00

H. PYLORI I – HALL 7__________

P0542 EUROPEAN REGISTRY ON H. PYLORI MANAGEMENT (HP-EUREG): BACTERIAL RESISTANCE

A. G. Mcnicholl¹, A. Gasbarrini², B. Tepes³, D. S. Bordin⁴, F. Lerang⁵, M. Leja⁶, T. Rokkas⁷, D. Vaira⁸, O. Shvets⁹, L. Kupcinskas¹⁰, A. Perez-Aisa¹¹, A. Axon¹², G. M. Buzas¹³, M. Castro¹⁴, I. Simsek¹⁵, M. Katicic¹⁶, J. C. Machado¹⁷, V. Lamy¹⁸, K. Przytulski¹⁹, L. Rodrigo²⁰, L. Boyanova²¹, P. Bytzer²², C. Beglinger²³, L. G. Capelle²⁴, A. Goldis²⁵, L. Veijola²⁶, M. Vujasinovic²⁷, L. Bujanda²⁸, A. Huerta²⁹, L. Jonaitis³⁰, J. Molina-Infante³¹, M. Caldas¹, M. Ramas¹, M. Garcia-Donday¹, F. Megraud³², C. O'Morain³³, J. P. Gisbert¹, on behalf of Hp-EuReg Investigators

¹H. La Princesa & CIBERehd, Madrid, Spain, ²U.Sacro Cuore, Rome, Italy, ³AM DC, Rogaska, Slovenia, ⁴Clinical Sci. Centre, Moscow, Russian Federation, ⁵Central, Ostfold, Norway, ⁶University of Latvia, Riga, Latvia, ⁷Henry Dunant, Athens, Greece, ⁸University of, Bologna, Italy, ⁹University of, Kiev, Ukraine, ¹⁰U. Health Sci., Kaunas, Lithuania, ¹¹Costa del Sol, Malaga, Spain, ¹²University, Leeds, United Kingdom, ¹³Ferencvaros HC, Budapest, Hungary, ¹⁴Valme, Sevilla, Spain, ¹⁵Dokuz Eylul, Izmir, Turkey, ¹⁶Clinical H., Zagreb, Croatia, ¹⁷IPATIMUP, Porto, Portugal, ¹⁸CHU, Charleroi, Belgium, ¹⁹COI, Warsaw, Poland, ²⁰H. Central, Asturias, Spain, ²¹Med. U., Sofia, Bulgaria, ²²U. H., Koge, Denmark, ²³U. H., Basel, Switzerland, ²⁴Erasmus MC, Rotterdam, Netherlands, ²⁵CECH, Timisoara, Romania, ²⁶H, Herttoniemi, Finland, ²⁷Slovenj, Gradec, Slovenia, ²⁸H., Donosti, ²⁹H., Madrid, Spain, ³⁰UHSH, L, Lithuania, ³¹H., Cáceres, Spain, ³²H. Pellegrin, Bordeaux, France, ³³Trinity C, Dublin, Ireland

Introduction: Antibacterial resistance is one of the main causes of failed eradication attempt in the management of H. pylori.

Aims & Methods: To evaluate the resistance rates encountered by European Gastroenterologist in their routine clinical practice. A Local Coordinator was selected from each country with more than 10 H. pylori references in PubMed. Each Coordinator selected a representative group of recruiting investigators from his/her country. An e-CRF was created to systematically register all adult patients infected with H. pylori. Variables included: H. pylori diagnostic test used, use of culture and antibiogram, or molecular tests for the evaluation of antibiotic resistance.

Results: So far 11,272 patients have been included and 9,181 have finished follow-up. Culture was performed in 14% of naïve patients (prior to first-line treatment), 14% in second-line, 31% in third-line, and 25% in fourth-line. molecular tests to evaluate resistance were only performed in 0.3% of the cases. Table shows antibiotic resistance per antibiotic and line of treatment.

Abstract number: P0542

	Clarithromycin	Nitroimidazole	Clari + Nitro	Quinolone	Amoxicillin
1st line (naïve)	19% (16-22%)	29% (26-32%)	11% (9-13%)	14% (10-18%)	1% (0.5-1.5%)
2nd line	52% (45-57%)	45% (38-54%)	32% (26-38%)	16% (9-21%)	0% *
3rd line	64% (59-72%)	60% (52-70%)	53% (48-60%)	44% (39-50%)	0% *
4th line	72% (51-93%)	64% (43-80%)	64% (40-88%)	55% (31-69%)	0% *

* the sample size insufficient to draw conclusions

Numbers represent prevalence of resistant strains and 95% confidence intervals (in parenthesis)

Conclusion: The mean rate of H. pylori clarithromycin resistance in European naïve patients reaches the threshold established by consensus conferences (15-20%) in which empirical use of standard triple therapy should be discarded. There is a strong acquisition of antibiotic resistance after failed treatments.

Disclosure of Interest: None declared

P0543 EFFICIENCY OF 14-DAY AND SEQUENTIAL THERAPHY WITH LEVOFLOXACIN IN HELICOBACTER PYLORI ERADICATION

A. Soylu¹, S. Cakmak¹, Y. Okuturlar², I. Sevindir¹, S. Poturoglu³

¹Gastroenterology, ²Internal Medicine, Bakirkoy Dr Sadi Konuk Research and Training Hospital, ³Gastroenterology, Haseki Research and Training Hospital, Istanbul, Turkey

Contact E-mail Address: aliyesoylu@superonline.com

Introduction: Helicobacter pylori currently has different antibiotic combinations that are among therapy protocol options. In this study we researched levels of success of the 14-day and sequential therapy methods and whether previous experience of being treated in different combinations and existence of chronic ulcer are effective in eradication.

Aims & Methods: H. pylori cases were classified as the 14-day therapy group and the sequential therapy group in a randomized manner. Colloidal bismuth substrate (4x300mg) was used for 4 weeks, Esomeprazole (2x40mg) for 2 weeks, Amoxicillin (2x1000) and Levofloxacin (2x250mg) were used in the 14-day therapy group; and Colloidal bismuth substrate (4x300mg) for four weeks, Esomeprazole (2x40mg) for 2 weeks, Amoxicillin (2x1000) for the first week and Levofloxacin (2x250mg) for the second week and Metronidazole (3x500mg) were used in the sequential therapy group. Eradication success in each group was evaluated by means of a urea breath test conducted 8 weeks after the therapy.

Results: A total of 436 cases were included in the study. The cases were classified into two groups as the 14-day (118 female) and the sequential therapy group (128 female) (n=218). Average age group was 42.24 ± 13.046 in the 14-day therapy groups; while it was 45.10 ± 13.510 in the sequential therapy group. There were no difference of dispersion between groups in terms of gender (p=0.407) or number of previously-received (1,2 or 3) therapies (p=0.428). The ratio of the cases that had received previous therapy was 31.7% in the 14-day group; whereas in was 33.7% (n=69) in the sequential therapy group. The ratio of cases excluded from the study due to the side effects of drugs was determined to be 2.5% in the 14-day therapy group; whereas it was 2% (n=4) in the sequential therapy group; and there were no statistical differences between the groups (p=0.719). Eradication by therapy was 84.2% in the 14-day therapy group; and 80% in the sequential therapy group (p=0.274). Response to the therapy among those that had received previous therapy was 81.3% in the 14-day therapy groups and 72.5% in the sequential therapy group (p=0.055). Moreover; there was no meaningful correlation detected between the number of previous therapies received and response to the therapy [14-day (p=0.742), sequential (p=0.077)]. Non-response to the therapy in cases with ulcer/deformation in bulbus was 34.8% in the 14-day therapy group and 16% in the sequential therapy group. The side effects that were observed more in the sequential therapy in comparison with the 14-day therapy were bad taste in mouth (p=0.014), fatigue (p=0.026), inaccetence (p=0.006) and nausea (p=0.046).

Conclusion: Patient compliance in both therapy protocols was good. Having received standard therapy previously has no effect on eradication success. In spite of the frequent side effects of the therapy, they are well-tolerated and therapy cessation rate is low. High level of success in eradication was achieved in the 14-day and sequential therapies with the therapy combination with Levofloxacin. Nevertheless, eradication success level is lower than expected in quad therapy.

Disclosure of Interest: None declared

P0544 LACTOBACILLUS BULGARICUS GLB44 AND HELICOBACTER PYLORI INFECTION – INHIBITION OR POSSIBLE ERADICATION: PRELIMINARY CLINICAL RESULTS

B. Vladimirov¹, Y. Valerieva¹, I. Terziev², L. Boyanova³

¹Clinical Centre of Gastroenterology, ²Department of Pathology, University Hospital “Queen Joanna - ISUL", ³Department of Microbiology, Medical University of Sofia, Sofia, Bulgaria

Contact E-mail Address: yana_valerieva@abv.bg

Introduction: To evaluate the effect of Lactobacillus delbrueckii subsp. bulgaricus GLB44 in commercially available form on Helicobacter pylori infection in combination with a proton-pump inhibitor.

Aims & Methods: Fourteen patients (57.1% male and 42.9% female) at mean age 42 ± 13.2y were enrolled in our study after esophagogastroduodenoscopy. All patients were Helicobacter pylori (HP) positive diagnosed either by rapid urease test, stool antigen test and histology examination, or by a combination of these methods. Every patient was given Lactobacillus bulgaricus GLB44 (capsules and tablets) in daily doses of 15x10⁹ living cells together with Rabeprazol 20 mg bid for 7 days, followed by GLB44 alone for 3 days at the same dose. Control stool immunochromatographic antigen tests were performed in all patients after at least 43 days.

Results: After the course of treatment 92.9% of the previously HP positive patients had negative control stool antigen tests. The single case still positive had two unsuccessful antimicrobial eradication courses in the past, while the rest of the group was treatment-naive.

Conclusion: Lactobacillus delbrueckii subsp. bulgaricus has in vitro inhibitory properties against H. pylori.¹ Per oral route of administration of adequate probiotic dose in combination with PPI is a promising treatment modality in HP positive patients.

Disclosure of Interest: None declared

P0545 RANDOMIZED OPEN LABELED CLINICAL TRIAL: A COMPARATIVE STUDY OF 10-DAY HIGH DOSE PPI TRIPLE THERAPY VS. 10-DAY SEQUENTIAL THERAPY FOR HELICOBACTER PYLORI ERADICATION IN FUNCTIONAL DYSPEPSIA PATIENTS

M. Maneerattanaporn¹, C. Auesomwang², P. kiratisin¹, S. leelakusolwong¹

¹Internal Medicine, Division of Gastroenterology, ²Internal Medicine, Division of ambulatory medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand

Contact E-mail Address: monthira.man@mahidol.ac.th

Introduction: Eradication rates following standard triple therapy for Helicobacter pylori (HP) infection are declining worldwide. Studies suggest that high-dose proton-pump inhibitor (PPI)-based triple therapy and sequential therapy for HP infection may yield higher cure rates than standard triple therapy.

Aims & Methods

Objectives: To compare the efficacy and tolerability of high dose PPI-based triple therapy and sequential therapy in adults with Helicobacter pylori associated functional dyspepsia.

Methods: One hundred twenty patients with HP positive functional dyspepsia (FD) were prospectively randomized to receive 10-day high dose PPI triple therapy (HD PPI TT) group [60 mg of lansoprazole, 500 mg of clarithromycin, and 1 g of amoxicillin, each administered twice daily for 10 days] or 10-day sequential therapy (ST) group [30 mg of lanzoprazole, 1 g of amoxicillin, each administered twice daily for the first 5 days, followed by 30 mg of lanzoprazole, 500 mg of clarithromycin, and 500 mg of metronidazole, each administered twice daily for the remaining 5 days]. HP status was determined at the 4^th week post treatment by the ¹⁴C-urea breath test. Eradication rates, antibiotic resistance rates, dyspeptic symptoms, drug compliance, and adverse effects were compared.

Results: The eradication rates in the ST and HD PPI TT groups, were comparable by the ITT analysis [85% (95% CI 73.4-92.9) vs. 80% (95% CI 67.7-89.2), P=0.471] In the PP analysis, although ST yielded a higher eradication rate than HD PPI TT [94.4% (95% CI 84.6-98.8) vs. 81.4% (95% CI 69.1-90.3), p=0.035]. Clarithromycin resistance was identified in 10% of isolates. Cure rates with ST were significantly higher than HD PPI TT in patients with clarithromycin-resistant HP strains (100% vs. 33.3%; P = 0.02). Compliance with the treatments was similar (98.3% with HD PPI TT and 93.1% with ST; P = 0.20). Nausea (p=0.03) and dizziness (p=0.03) were more common with ST group than HD PPI TT.

Conclusion: In Thailand, ST yielded higher eradication rate than HD PPI TT, in HP associated functional dyspepsia. This was in both in overall FD patients and in a subgroup of clarithromycin resistance. However, the eradication rate of sequential therapy was declined from 94.4% (PP analysis) to only 85% (ITT analysis). The adverse effects of sequential therapy caused lower adherence and might compromise the overall efficacy of ST.

Disclosure of Interest: M. Maneerattanaporn Financial support for research: Pharmaceutical company, C. Auesomwang Financial support for research: Pharmaceutical company, P. kiratisin: None declared, S. leelakusolwong: None declared

P0546 QUADRUPLE THERAPY IN THE ERRADICATION OF HELICOBACTER PYLOTI – THE NEW PARADIGM IN A SOUTHERN EUROPEAN COUNTRY

D. Branquinho¹, N. Almeida¹, A. Casela¹, M. Donato¹, C. Calhau¹, C. Sofia¹

¹Gastroenterology, Coimbra University Hospital (CHUC), Coimbra, Portugal

Contact E-mail Address: diogofbranquinho@yahoo.com

Introduction: Empiric triple therapy to eradicate Helicobacter pylori (Hp) in Portugal has shown a high failure rate. As such, quadruple regimens should be adopted as first-line therapy. However, due to the simultaneous resistance rate to metronidazole and clarithromycin (5,8%), the efficacy of the sequential therapy may be compromised.

Aims & Methods: Our objective was to evaluate the success rate, in current clinical practice, of the sequential quadruple scheme in naïve patients. Additionally, we searched for factors that could influence Hp eradication rates.

A total of 250 patients (female – 148; average age – 51.7 ± 15.6 years-old) were treated with sequential scheme (PPI and amoxicillin for 5 days, followed by PPI plus clarithromycin and metronidazole/tinidazole in the next 5 days). Bacterial eradication was checked by Urea Breath Test (UBT). Several clinical and demographic variables that could affect the success rate were analyzed (age, gender, smoking habits, dosage and type of PPI used, metronidazole regimen, use of metronidazole vs tinidazole).

Results: The overall success rate was 90.4% (IC95%: 86.1-93.5%). The most frequent indications for eradication were dyspepsia (58.4%), evaluation before bariatric surgery (12.4%) and peptic ulcer disease (10.8%). Both in the univariate and multivariate analysis, taking metronidazole every 8 hours was more effective than the 12-12 hour regimen (96.5% vs 53.8%, p=0.002) and the same was noted for full-dose of PPIs when compared to of half-dose (97.8 vs 41.7%, p=0.002). No other factor had a significant impact on the success rate.

Conclusion: Despite the described high primary resistance rates to both clarithromycin and metronidazole, sequential therapy was quite effective in clinical practice. However, full-dose PPI and an 8-8 hour metronidazole regimen must be adopted to achieve a positive outcome. It is fundamental to conduct another prospective study comparing different quadruple regimens.

Disclosure of Interest: None declared

P0547 COMPARISON OF H.PYLORI ERADICATION RATE IN TWO QUADRUPLE REGIMEN “AMOXICILLIN, BISMUTH SUBCITRATE, PANTOPRAZOLE, CLARITHROMYCIN “WITH “AMOXICILLIN, BISMUTH SUBCITRATE, PANTOPRAZOLE AND GEMIFLOXACIN"

F. Mansour-Ghanaei¹, A. Shafaghi¹, F. Joukar¹, Z. Pedarpour Vajargah¹

¹Gastrointestinal & Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran, Islamic Republic Of

Contact E-mail Address: ghanaie@yahoo.com

Introduction: H.pylori infection is the most bacterial infection in human. Gastritis, peptic ulcer, lymphoma and gastric adenocarcinoma are the outcomes of H.pylori infection. According to increase of drug resistance some studies have been done about the role of Floroquinolons in the treatment of H.pylori infection. In vitro studies showed the efficacy of Gemifloxacin against H.pylori infection.

Aims & Methods: The aim of this study was comparison of H.pylori eradication rate in two quadruple regimens “Bismuth subcitrate, Pantoprazole, Amoxicillin, Clarithromycin” with “Bismuth subcitrate, Pantoprazole, Amoxicillin, Gemifloxacin”.

In a randomized clinical trial, a total of 182 H.pylori positive patients older than 18 years and less than 80 years were enrolled. For all patients information form includes name, age, sex, smoking history was recorded. 91 patients (50%) were treated with BPAC regimen (Bismuth subcitrate 240mg BID, Pantoprazole 20mg BID, Amoxicillin 1gr BID, Clarithromycin 500mg BID) and 91patients (50%) were treated with BPAG regimen (Bismuth subcitrate 240mg BID, Pantoprazole 20mg BID, Amoxicillin 1gr BID,Gemifloxacin 320mg daily) for 10 days. 12 weeks after completion of therapy the eradication was confirmed by a C14 urease breath test.

Results: Three patients were excluded from the study due to drug complications that were a man and a woman due to severe diarrhea, severe Nausea and Vomiting from BPAC group and a woman due to severe Nausea and mouth sores from BPAG group. Thus, 179 patients completed the course of treatment. The eradication rates in the BPAC and BPAG regimens with per-protocol and intention-to-treat analysis was reported 91% vs 77.8%, P-value = 0.015 and 89% vs 76.9%, P-value = 0.03, respectively. No relation between age, sex and smoking with eradication rates was reported, except association of age with BPAG regimen (P-value = 0.03).

Conclusion: In this study, the eradication rates with BPAG regimen in PP and ITT analysis were 77.8% and 76.9% respectively, therefore BPAG regimen was not succeeded in eradication of H.pylori infection.

Disclosure of Interest: None declared

P0549 A NEW GENERATION OF COLD-SHOCK EXPRESSION VECTOR DERIVED FROM PCOLD I (PCOLD I-LZ) FOR DIRECTIONAL CLONING AND RECOMBINANT EXPRESSION OF ANTI-HELICOBACTER PYLORI AND ANTI-GASTRIC CANCER STEM CELLS (GCSCS) SMALL PEPTIDES

H. Latifi-Navid¹, S. Latifi-Navid¹, S. Zahri¹

¹Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran, Islamic Republic Of

Contact E-mail Address: hlatifin@gmail.com

Introduction: Current treatment of Helicobacter pylori infection has several inherent problems such as the emergence of resistance to the antibiotics used and associated adverse effects, the risk of reinfection or recrudescence, and the high cost of treatment. On the other hand, cancer stem cells (CSCs) have the ability to create tumour and promote its regeneration. These cells are responsible for gastric cancer progression, recurrence, and metastasis. It seems that the use of anti-H. pylori and anti-gastric CSCs peptides can provide a new therapeutic strategy for the treatment of this disease. Today, the recombinant expression approach is a useful and economical tool to the high-scale production of therapeutic nano-peptides. However, the short length of the peptides is a limiting factor in the realization of this approach. This is because one or more amino acid residues are added during the cloning process that leads to the loss of the original peptide folding and influences its function.

Aims & Methods: The aim of the present study was to change the structure of the pCold I vector using site-directed mutagenesis in order to do the directional cloning of each target gene and express/purify the small peptides and native proteins with no any additional N-terminus amino acids.

Results: In fact, the structure of the vector was changed such that the cut sites of both the first restriction enzyme at the multiple cloning site (at the nucleotide level) and factor Xa (at the amino acid level) to be the same. The TEE, His6-tag, and factor Xa site were removed by using the factor Xa, leaving no extra N-terminal residues.

Conclusion: The modified vector can be widely used to a fast and more convenient cloning and expression of the native proteins and short peptides, including anti-H. pylori peptides (e.g. Magainin 2 and Odorranain-HP) and anti-angiogenesis (e.g. Anginex), gastric anti-CSCs and anti-metastatic peptides.

Disclosure of Interest: None declared

P0550 CLINICAL OUTCOME OF ERADICATION THERAPY FOR GASTRIC MUCOSA-ASSOCIATED LYMPHOID TISSUE LYMPHOMA ACCORDING TO HELICOBACTER PYLORI INFECTION STATUS

H. S. Moon¹, J. S. Kim¹, S. H. Kang¹, J. K. Sung¹, H. Y. Jeong¹

¹Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea

Contact E-mail Address: mhs1357@cnuh.co.kr

Introduction: Helicobacter pylori (H. pylori) eradication is the first-line therapy for H. pylori-positive localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma. But the management of the H. pylori-negative gastric MALT lymphoma remains controversial.

Aims & Methods: Therefore we assess the efficacy of eradication therapy according to H. pylori infection status and find out a predictive factor for resistance to treatment. We retrospectively reviewed the chart with gastric MALT lymphoma between January 2001 and June 2014. The basal characteristics and clinical outcome was compared between H. pylori-positive and H. pylori-negative gastric MALT lymphoma groups.

Results: Total 54 patients were enrolled and 12 patients were H. pylori-negative. H. pylori-negative patients were significantly multiple lesion (P = 0.045) and the lesion presence of both proximal and distal part of stomach (P = 0.001) than H. pylori-positive patients. 47 patients received eradication as an initial therapy. 85% (35/41) H. pylori-positive patients achieved complete remission and 50% (3/6) H. pylori-negative patients obtained regression after eradication therapy. Eradication therapy efficacy was no significant difference between two groups (P = 0.133). Multiple lesion was predictive factor for unresponsiveness to H. pylori eradication (P = 0.024).

Conclusion: In case of H. pylori-negative gastric MALT lymphoma eradication therapy could be considered as an initial therapeutic option especially for patients with a single lesion.

Disclosure of Interest: None declared

P0551 CLINICAL OUTCOMES AND INFLUENCING FACTORS OF THE STANDARD TRIPLE THERAPY PLUS PROBIOTICS AND CONCOMITANT THERAPY FOR FIRST-LINE TREATMENT OF HELICOBACTER PYLORI INFECTION

I. K. Cho¹, J. H. Lim¹, C. H. Lee¹, H. J. Kang¹, J. G. Jung¹, D. Y. Oh¹, S. H. Oh¹

¹Internal Medicine, Incheon Sarang Hospital, Incheon, Republic of Korea

Contact E-mail Address: medfd@naver.com

Introduction: Since the efficacy of the standard triple therapy for Helicobacter pylori eradication has decreased, there have been attempts to increase the eradication rate by the addition of a potentially helpful drug to the standard triple regimen. Among these, the standard triple therapy plus probiotics (STP) and the concomitant therapy (CT) were introduced and showed encouraging results.

Aims & Methods: We aimed to compare the efficacies and analyze the influencing factors of both regimens. From Mar. 2013 to Feb. 2014, a total of 363 patients who received one of the STP regimen (n=288, standard-dose proton-pump inhibior +clarithromycin 500mg + amoxicillin 1g + probiotic preparation, b.i.d. for 1 week) and the CT regimen (n=75, standard-dose PPI +clarithromycin 500mg + amoxicillin 1g + metronidazole 500mg, b.i.d. for 1 week) for H. pylori eradication were included. Probiotic bacteria composed of Bacillus subtilis and Lactobacillus rhamnosus. H. pylori status was evaluated at least 4 weeks later, after completion of treatment by ¹³C-urea breath test.

Results: The intention-to-treat and per-protocol eradication rates were 83.3% (95% CI, 78.8-87.5) and 86.9% (95% CI, 82.6-91.1) in the STP group, and 86.7% (95% CI, 78.7-94.7) and 91.4% (95% CI, 84.5-97.3) in the CT group. There were no significant between-group differences, in regard to the eradication rates and compliance. In the STP group, however, the incidence of side effects was significantly lower than the CT group (13.0% vs 28.2%, p=0.002). The most common side effects were dyspepsia, nausea and dry mouth. In the multivariate analysis, older age in the STP group, and female sex, diabetes and alcohol drinking in the CT group were independent factors associated with eradication failure.

Conclusion: Both treatment regimens showed encouraging efficacies for H. pylori eradication. In the aspect of side effects, the addition of probiotics to the standard triple therapy may be a reasonable option. More large sample sized prospective study will be needed.

Disclosure of Interest: None declared

P0552 FOURTEEN- VERSUS SEVEN-DAY BISMUTH-BASED QUADRUPLE THERAPY FOR SECOND-LINE HELICOBACTER PYLORI ERADICATION

J. J. Hwang¹, D. H. Lee¹, H. Yoon¹, C. M. Shin¹, Y. S. Park¹, N. Kim¹

¹Department of Internal medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea

Contact E-mail Address: frontierassa@hanmail.net

Introduction: To compare the efficacy of 14- and 7-day bismuth-based quadruple therapies as second-line eradication treatment for Helicobacter pylori infection.

Aims & Methods: Between 2004 and 2014, the medical records of 790 patients who had experienced failure of first-line proton pump inhibitor (PPI)-based eradication therapy and were then treated with bismuth-based quadruple therapy were retrospectively reviewed. Those who received bismuth-based quadruple therapy (PPI, bismuth, metronidazole, and tetracycline; PBMT) for either 7 days or 14 days were assigned to a PBMT-7 group (n = 543) or a PBMT-14 group (n = 247), respectively. The eradication rates for both groups were determined by intention-to-treat (ITT) and per-protocol (PP) analyses. ITT analysis compared the treatment groups as originally allocated while the PP analysis including only those patients who had completed the treatment as originally allocated. Successful eradication therapy for H. pylori infection was defined as a negative 13C-urea breath test 4 weeks after the end of eradication treatment.

Results: The overall ITT eradication rate was 69.1% (546/790). Final ITT eradication rates were 67.4% (366/543; 95% confidence interval [CI]: 63.1–71.7%) in the PBMT-7 group and 72.8% (180/247; 95% CI: 67.4–78.2%) in the PBMT-14 group (p = 0.028). The overall PP eradication rate was 80.0% (546/682), and the final PP eradication rates were 78.2% (366/468; 95% CI: 72.1–84.0%) in the PBMT-7 group and 84.1% (180/214; 95% CI: 76.8-90.8%) in the PBMT-14 group (p = 0.009). The H. pylori eradication rates in the PBMT-14 group were significantly higher than in the PBMT-7 group according to both ITT (p = 0.028) and PP analysis (p = 0.009). Compliance was similar in both groups (PBMT-7 group: 97.9%; PBMT-14 group: 96.4%). Adverse event rates were 10.7% (51/478) and 17.1% (38/222) in the PBMT-7 and PBMT-14 groups, respectively (p = 0.487).

Conclusion: The H. pylori eradication rates in the PBMT-14 group were significantly higher than in the PBMT-7 group according to both ITT and PP analysis. The 14-day bismuth-based quadruple therapy is a significantly more effective second-line eradication treatment for H. pylori infection than the 7-day alternative.

Disclosure of Interest: None declared

P0553 PRENEOPLASTIC GASTRIC LESIONS IN PATIENTS WITH MALT LYMPHOMA: COMPARISON WITH DIFFUSE LARGE B-CELL LYMPHOMA AND H PYLORI ASSOCIATED CHRONIC GASTRITIS

A.-L. Rentien¹, A. Amiot¹, C. Copie-Bergman², M. Levy¹, Y. Le Baleur¹, F. Mesli¹, H. Bessalem¹, C. Haioun³, I. Sobhani¹, J.-C. Delchier¹

¹Gastroenterology, ²Pathology, ³Hematology, Henri Mondor, Créteil, France

Contact E-mail Address: alrentien@gmail.com

Introduction: Patients with primary gastric MALT lymphoma (GML) are at risk of developing gastric carcinoma GC even after completing remission. The aim of this retrospective study was to assess the prevalence and the course of preneoplastic lesions in patients with GML as compared with gastric diffuse large B-cell lymphoma (GDLBCL) and H. pylori-associated chronic gastritis (HpG).

Aims & Methods: From 1990 to 2013, 179 patients with GML, 70 with GDLBCL and 152 patients with HpG, were included. Clinical, biological, endoscopic and histopathological parameters were reviewed. To assess the presence or absence of preneoplastic lesions, we reported the Sydney score in 3 gastric areas (antrum, corpus and lymphoma site). Atrophy > 2 was only considered as significant. Preneoplastic lesion-free survival was assessed using Kaplan-Meier method, log-rank test and Cox model. Patients’ characteristics were compared using chi² and Wilcoxon-Mann-Whitney tests.

Results: The median follow-up of GML patients was 6.5 (0.1-33.7) years. At the time of diagnosis, 119 (66%) patients presented with a H. pylori infection. GML was located at the junction of the body with antrum in 43% of the cases with a pseudogastritis appearance in 57%. At the inclusion, atrophy and metaplasia were observed in 35% and 25%, respectively. Both atrophy and metaplasia were more frequently located in the lymphoma site as compared with antrum and corpus. Dysplasia was observed in 3% of the cases. To assess the course of preneoplastic and neoplastic lesion, we analysed a subgroup of 104 patients followed-up for at least five years. Although the overall prevalence of atrophy remained stable over time with the evidence of incidental and regressive atrophy, the prevalence of metaplasia tended to increase at the lymphoma site. In the overall population of 179 patients, the probabilities of atrophy were 24%, 39% and 48% at 1, 5 and 10 years. The probabilities of metaplasia were 12%, 30% and 36% and the probabilities of dysplasia or GC were 9, 16 and 22%, respectively. Nine cases (5 women, 4 males) presented with a gastric cancer during follow-up, all associated with underlying preneoplastic gastric lesions. The median delay before the occurrence of GC was 2.49 (0-16.66) years. At diagnosis, significant atrophy and metaplasia were significantly more frequent in GML group vs. GDLBCL group (19% and 14%) and versus hpG (8% and 15%), respectively. No dysplasia was observed in both control groups.

Conclusion: The occurrence of preneoplastic and neoplastic gastric lesions in patients with GML is frequent and still increases overtime at the lymphoma site despite complete remission of the lymphoma. The occurrence of such lesions is higher than in patients with GDLBCL and HpG suggesting a deleterious effect of GML on the gastric epithelia cells that lead to the occurrence of these lesions. Long-term follow-up is warranted to detect gastric neoplasia at an early stage.

Disclosure of Interest: None declared

P0554 PRIMARY GASTRIC LYMPHOMA – EXPERIENCE OF A TERTIARY CENTER

A. G. Antunes¹, M. Eusébio¹, A. Vaz¹, P. Queirós², T. Gago¹, B. Peixe¹, H. Guerreiro¹

¹Gastroenterology Department, Centro Hospitalar do Algarve, Faro, ²Gastroenterology Department, Centro Hospitalar do Algarve, Portimão, Portugal

Contact E-mail Address: sergiogiao@hotmail.com

Introduction: In the immunocompetent patient, the gastrointestinal tract is the most common extranodal site for lymphoma. However, primary gastrointestinal lymphomas are very rare, accounting for only 1-4 % of all gastrointestinal malignancies. The stomach is the most commonly affected site, corresponding to less than 3% of gastric malignancies and 10% of all lymphomas. Approximately 90% of cases of primary gastric lymphomas (PGLs) are either mucosa-associated lymphoid tissue (MALT) lymphoma or diffuse large B-cell lymphoma (DLBCL). Although it’s well established the relation between MALT lymphoma and Helicobacter pylori (Hp) infection, significant controversy exists regarding the role of Hp infection in the pathogenesis of DLBCL (specially, in those that develop from a MALT lymphoma).

Aims & Methods: (1) To describe the experience of a tertiary center in the diagnosis, management and follow-up of PGLs; (2) To compare clinical, laboratorial, histological (Hp infection) and endoscopic features at presentation, between the MALT and DLBCL subtypes.

All new cases of PGL were retrospectively evaluated between 1996 and 2014. Primary gastrointestinal lymphoma was defined according to Dawson criteria. Staging was established according to Lugano staging system, and for risk assessment International Prognostic Index (IPI) was used. We recorded demographic, clinical, laboratorial endoscopic and radiological data.

Results: We identified 31 patients, with a mean age of 65 years old, a male preponderance (n=20) and 5 patients had ECOG ≥2. The most common subtype was MALT (n=18), followed by DLBCL (n=11). The most frequent symptom was abdominal pain (62%), followed by anorexia (55%), while the classical B symptoms were only present in two patients; 10 patients had Hb <12.0 g/dL at presentation (none with DLBCL subtype).

At diagnosis, 80% of the cases were classified as limited disease (Lugano: I-II) and 84% as having low or intermediate risk (IPI ≤ 2), with no statistically significant differences between MALT and DLBCL subtypes. The most common endoscopic pattern was ulcerative type (62%), and gastric body was affected in 69%, with no statistically significant differences between the subtypes.

The variables age, Leukocyte count, serum LDH, Albumine, Urine Acid and β-2 microglobuline weren’t statistically different between MALT and DLBCL subtypes. Hp infection was present in 11 patients (MALT: 10; DLBCL: 1; p=0.022). The mean survival was 67 months (MALT: 80.7 versus DLBCL 38).

Conclusion: Although the small number of patients, our data does not support the role of Hp in the pathogenesis of DLBCL lymphoma. Beside anemia, none of the studied variables at presentation, was statistically different between the subtypes. The results agree and strengthen the scarce available literature about PGLs.

Disclosure of Interest: None declared

P0555 HELICOBACTER PYLORI VACA GENOTYPES PREDICT RISK OF INTESTINAL- AND DIFFUSE-TYPE ADENOCARCINOMAS IN A VERY HIGH-RISK AREA IN IRAN

E. Abdi¹, S. Latifi-Navid¹, S. Zahri¹, A. Yazdanbod²

¹Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, ²Gastrointestinal Cancer Research Center, Ardabil University of Medical Sciences, Ardabil, Iran, Islamic Republic Of

Contact E-mail Address: abdi.esmat@yahoo.com

Introduction: Gastric cancer (GC) is the fifth commonest malignant disease throughout the world and the third-leading cause of cancer-related mortality, and histo-morphologically is divided into two groups; intestinal- and diffuse-type carcinomas. Helicobacter pylori infection is one of the main risk determinants of both the type of GC. Ardabil in Northwestern Iran has the highest rates of H. pylori infection (89%) and stomach cancer, in which it constitutes the 31% of all malignancies seen in this area with the ASRs of 51.8/100,000 for males and 24.9/100,000 for females. In this province, greater than 90% of adults aged 40 or older are suffering from chronic gastritis related to H. pylori infection.

Aims & Methods: We aimed to investigate the frequency of the H. pylori vacA (vacuolating cytotoxin A) gene polymorphisms and their associations with the intestinal- or the diffuse-type adenocarcinomas in Ardabil. We determined the presence of the H. pylori 16S rDNA gene, and also the vacA s-, m-, i-, and d-region genotypes in gastric biopsies, and performed histopathological evaluations. Associations between the H. pylori vacA allelic variants and whether the intestinal- or the diffuse-type adenocarcinomas were assessed by the χ2 test or Fisher’s exact test where appropriate. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were computed. The Forward Stepwise LR (Likelihood Ratio) multiple logistic regression was used for each genetic variant individually, with adjustment for age and sex.

Results: Of 135 patients, 57 with non-atrophic gastritis and 78 with gastric cancer (GC), 103 were infected by H. pylori. In patients with the intestinal-type adenocarcinoma of the stomach, the vacA s1, m1, i1, and d1 genotypes were detected in the 47.8%, 63.2%, 84.2%, and 76.5% of H. pylori strains, respectively, while in patients with the diffuse-type adenocarcinoma of the stomach, the vacA s1, m1, i1, and d1 genotypes were present in the 73.3%, 42.9%, 66.7%, and 76.9% of strains, respectively. The frequency of the vacA i1 and d1 genotypes was significantly higher in patients with the intestinal-type adenocarcinoma (84.2%, and 76.5%, respectively) than in those with NAG (47.1% and 45.0%, respectively); the OR was 6.00 (95% CI, 1.47-24.45; P = 0.01) and 3.97 (95% CI, 1.10-14.31; P = 0.042), respectively. However, in multiple logistic regression with adjustment for age and sex, only the vacA i1 genotype was significantly associated with an increased risk of the intestinal-type adenocarcinoma (OR = 14.04, 95% CI, 2.15-91.77; P = 0.006). Although the adjusted OR of 4.08 (95% CI, 0.95-17.50) was obtained for d1, the difference did not reach significance (P = 0.058). The presence of the vacA d1 genotype was significantly associated with an increased risk of the diffuse-type adenocarcinoma in the multiple logistic regression (OR = 7.71, 95% CI, 1.13-52.28; P = 0.036).

Conclusion: It is proposed that the vacA i1 and d1 genotypes might be important for the prediction of the risk of the intestinal- and the diffuse-type adenocarcinomas, respectively.

Disclosure of Interest: None declared

P0556 H. PYLORI INFECTION WITH ATROPHIC GASTRITIS IS AN INDEPENDENT RISK FACTOR FOR ADVANCED COLONIC NEOPLASM

J. Y. Lee¹, H. W. Park¹, J. Y. Choi¹, J.-S. Lee¹, J. E. Koo¹, E. J. Chung¹, H.-S. Chang¹, J. Choe¹, D.-H. Yang², S.-J. Myung², H.-Y. Jung², S.-K. Yang², J.-S. Byeon²

¹Helath Screening and Promotion Center, ²Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

Contact E-mail Address: living_stone@hanmail.net

Introduction: Helicobacter pylori (H. pylori) infection is a major risk factor for atrophic gastritis (AG) and gastric cancer and can induce various extragastric malignancies, but its relationship to colorectal neoplasm (CRN) remains unclear. The correlation between AG and CRN has been little studied and is inconclusive.

Aims & Methods

Aim: The aim of this study was to investigate the association between H. pylori infection status, AG, and advanced CRN.

Methods: This cross-sectional study investigated the relationship between the presence of serum anti-H. pylori IgG antibody, AG, and advanced CRN in 6,351 consecutive asymptomatic subjects who underwent screening colonoscopy. Multivariate analysis was performed including clinical variables such as gender, age, family history of colorectal cancer, smoking status, alcohol consumption, presence of metabolic syndrome, and endoscopic findings.

Results: A total of 316 participants (5.0%) had advanced CRN. H. pylori seropositivity was found in 61.3% of these cases. In univariate analysis, the presence of H. pylori infection was associated with overall CRN (OR 1.33, 95% CI 1.19–1.48; p < 0.001) and advanced CRN (OR 1.49, 95% CI 1.17–1.91; p = 0.001). H. pylori infection was associated with an increased risk of advanced CRN after adjusting clinically relevant confounders (OR 1.34, 95% CI 1.04–1.72; P = 0.023). H. pylori-related AG was significantly associated with the risk of advanced CRN (OR 1.40, 95% CI 1.03–1.91; p = 0.030), whereas H. pylori infection without AG was not.

Conclusion: H. pylori infection increases the risk of advanced CRN, especially when combined with AG. Strict colonoscopy screening and surveillance may be warranted in H. pylori-positive AG patients.

Disclosure of Interest: None declared

P0557 INCIDENCE OF SECOND CANCERS IN PATIENTS WITH GASTRIC MALT LYMPHOMA

J. Moleiro¹, S. Ferreira¹, P. Lage¹, A. Dias Pereira¹

¹Gastroenterology, Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E., Lisboa, Portugal

Contact E-mail Address: joana_moleiro@hotmail.com

Introduction: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is closely associated with Helicobacter pylori infection. The incidence of second cancers, namely gastric carcinoma, seems to be increased in this group of patients. However, the evidence is still controversial.

Aims & Methods: To determine the incidence of second cancers in patients with gastric MALT lymphoma who achieved complete remission, we evaluated consecutive patients admitted with gastric MALT lymphoma (1994-2014), staged according to the Ann Arbor staging system modified by Musshoff´s. Patients' characteristics, the diagnosis of second cancers and survival were recorded. Standardized incidence ratio (SIR), using age- and sex-specific incidence rates from the Cancer Registry, was calculated.

Results: A total of 143 patients (76 men) were included with a mean age of 56 years (18-83); 103, 24 and 16 patients were diagnosed at stages EI, EII and EIV, respectively. Complete remission was achieved in 128 patients. After a mean follow-up of 109 months (6-246), a second cancer was diagnosed in 14 (9.8%) patients (11 men, mean age of 66 years), in whom complete remission was achieved after eradication therapy (n=12), surgery (n=1) and chemotherapy (n=1). A total of 7 solid (lung (n=1), brain (n=1), liver (n=1), breast (n=1), pancreas (n=1), sarcoma (n=1) and colon (n=1)) and 7 hematologic cancers (non-Hodgkin lymphoma (n=4), Hodgkin lymphoma (n=1), multiple myeloma (n=1) and chronic myelomonocytic leukemia (n=1)) were reported. The non-Hodgkin lymphomas diagnosed were diffuse large B-Cell lymphoma (n=2), chronic lymphocytic leukemia (n=1) and parotid MALT lymphoma (n=1). There was an increased incidence of an additional cancer (SIR=1.4, p=0.0001) and non-Hodgkin lymphomas (SIR=9.3, p=0.04). The 10-year overall survival of the 128 patients that achieved complete remission was 82%. The cause of death was the second cancer in 11/24 (45.8%) patients.

Conclusion: Patients with gastric MALT lymphoma are at an increased risk for a second cancer, particularly non-Hodgkin lymphoma, which highlights the importance of a long-term follow up. There were no patients with gastric carcinoma. The overall prognosis was good but the occurrence of second cancers, mainly hematologic, were an important cause of death.

Disclosure of Interest: None declared

P0558 APPLICATION OF ABC SYSTEM INTO CLINICAL PRACTICE IN KOREA: IS IT WORTHWHILE?

J. Heo¹, S. W. Jeon¹, S. K. Kim¹, H. M. Yang¹

¹Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea

Contact E-mail Address: hero797@hanmail.net

Introduction: ABC method, which using a combination of serum Helicobacter (Hp) immunoglobulin G (IgG) and pepsinogen (PG) level, has been expected as a promising simple screening tool for gastric cancer. Group A is Hp infection-free subjects, Group B is Hp infected, but has no or minimal changes of atrophy, Group C has both positive result of serum value. Group D is the advanced infected type, which has extensive atrophy and negative Hp IgG which means relatively prior Hp infection.

Aims & Methods: We aimed to validate the ABC method for gastric cancer patients in clinical practice. The presence of Hp infection is determined by serum Hp IgG. The positive PG is defined as PG l level less than 70 ng/ml and the ratio of PG l/ll is less than 3.0. According to our strategy for gastric tumor since 2007, we have conducted the serum Hp IgG and PG level for the patients who plan to undergo endoscopic resection. We retrospectively reviewed the patients who underwent serum Hp IgG and PG level between October 2007 and November 2013 in Kyungpook National University Hospital in Korea.

Results: 1,146 cases were possible to be analyzed in ABC method. 717 patients were male and the mean age was 61.4 ± 10.3 years. Among 429 patients with gastric cancer, 82 patients (19.1%) were classified into Group A, 230 (53.6%) into Group B, 89 (20.7%) into Group C, and 28 (6.5%) into Group D, respectively. Group A also occupied considerable portion (15.9%) in gastric tumor including adenoma.

Conclusion: Considering relatively high prevalence of Helicobacter in Korea, the ABC method needs reconsideration before application in the screening for gastric cancer. In addition, other gastric cancer risk factors or confounding factors should be revealed, especially for group A patients in further study.

Disclosure of Interest: None declared

P0559 HELICOBACTER PYLORI VACUOLATING CYTOTOXIN GENOTYPES AND GASTRIC PRENEOPLASTIC LESIONS OR GASTRIC CANCER RISK: A COMPREHENSIVE META-ANALYSIS

S. Latifi-Navid¹, E. Abdi¹, H. Latifi-Navid¹, B. Safarnejad²

¹Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, ²School of Medicine, Tehran University of Medical Sciences, Tehran, Iran, Islamic Republic Of

Contact E-mail Address: saeid.latifinavid@gmail.com

Introduction: Disease progression to gastric cancer (GC) occurs in only a small proportion of H. pylori-infected patients. A considerable differences in the vacuole-creating activities are observed between H. pylori strains, which is attributed to the extensive polymorphisms within the vacuolating cytotoxin gene A (vacA). These variations may determine the clinical consequences; however, the association evidence is not totally consistent both between and within continents, and thus the actual influence of each allelic variant is still controversial.

Aims & Methods: We examined the strength of this association in adult-infected populations and modeled the impact of mean age-standardized incidence rates (ASRs) of GC as a hypothesized moderator variable. Pooled relative risk (RR) estimates were calculated. Subgroup, sensitivity, and meta-regression analyses were conducted.

Results: Totally, 33 studies, including 1446 cases and 2697 controls, were analyzed. The vacA s1 genotype was significantly associated with an increased risk of atrophic gastritis (AG), intestinal metaplasia (IM), and GC (RR=1.116, 95% CI,1.019-1.222, RR=1.418, 95% CI,1.035-1.942, and RR=1.333, 95% CI,1.115-1.593, respectively); however, the vacA m1 genotype strongly increased the risk of IM and GC, but not AG (RR=1.571, 95% CI,1.247-1.980 and RR=1.431, 95% CI,1.180-1.735, respectively). The vacA s1m1 allelic combination was linked to an increased risk of GC. The m1-type of vacA was more potent than s1 for predicting the risk of GC within the subgroups with mean ASRs 11/100,000-19/100,000 and less than 10/100,000, which was confirmed either by excluding the studies with the largest variance or by performing a leave-one-out analysis. The meta-regression analysis indicated that the ASR of GC modified the association between H. pylori genotypes and GC risk. When the ASRs of GC were used as a moderator variable, the estimated coefficient in predicting the logit was -0.0142, -0.0162, and -0.0160 for the vacA-s1, -m1, and –s1m1 genotypes, respectively, indicating that the estimated risk was significantly decreased with increasing the mean ASRs of GC (P-values=0.025, 0.00009, and 0.0005 for s1, m1, and s1m1,respectively).

Conclusion: H. pylori vacA-s1 and -m1 allelic variants strongly increased susceptibility to IM and GC; however, only s1 showed an association with AG. This association was largely influenced by geographic variation in the GC incidence rate.

Disclosure of Interest: None declared

P0560 HELICOBACTER PYLORI VACUOLATING CYTOTOXIN C1 GENOTYPE STRONGLY PREDICTS RISK OF CARDIA AND NON- CARDIA GASTRIC ADENOCARCINOMA

S. Z. Bakhti¹, S. latifi-navid¹, F. A. Bakhti²

¹Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran, Ardabil, ²Department of Biostatistics,, Faculty of Health, Mazandaran University of Medical Sciences, Sari, Iran, Islamic Republic Of

Contact E-mail Address: S.Z.Bakhti@gmail.com

Introduction: Gastric adenocarcinomas account for almost 90% of all gastric malignancies that are classified based on the anatomical site of tumor, including cardia gastric adenocarcinoma (CGA) and non-cardia gastric adenocarcinoma (NCGA).

Aims & Methods: We have recently identified a novel polymorphic site in the 3'-end region of H. pylori vacuolating cytotoxin gene A (vacA), denoted by c1/-c2 (c1: with deletion of 15 bp); thus we aimed to assess its association with the risk of CGA and NCGA in an Iranian population. A total of 593 patients who were of the rural and urban areas of Iran were participated in the study. Gastric biopsy specimens were taken from the antrum and/or the corpus, whether or not positive for rapid urease test, and then were cultured. The colonies were identified based on Gram staining, typical cell morphology, and positive reactions to catalase, oxidase, and urease, as well as PCR amplification of H. pylori 16S rDNA. The genotyping of the H. pylori vacA gene and histopathological examination and classification of subjects were then performed.

Results: Patients included 496 with non-atrophic gastritis (NAG), 41 with CGA, and 56 with NCGA. Of the 593 patients, 390 (65.8%) were positive for H. pylori infection, whereas 203 (34.2%) were negative. Statistical analysis showed no significant associations between the prevalence of H. pylori infection and sex, age, rural or urban areas and the risk of the CGA or the NCGA. The NCGA was more prevalent in rural areas [odds ratio (95% confidence interval) = 3.49 (1.86-6.57), P = 0.00]. Both the age >=55 and male gender were significantly associated with the CGA [OR (95% CI) = 17.85 (6.89-47.61) and 4.04 (1.89-8.62), respectively; P = 0.00] and the NCGA [OR (95% CI) = 17.24 (7.57-38.46) and 3.75 (1.97-7.19), respectively; P = 0.00]. A total of 173 H. pylori isolates, including 120 with NAG, 24 with CGA, and 29 with NCGA, were successfully obtained from biopsy cultures and genotyped. The frequency of the c1-type of vacA was higher in patients with both the CGA (83.3%) and the NCGA (71.4%) than in those with gastritis (NAG) (24.1%). The results of simple logistic regression analysis showed that this genotype was significantly associated with an increased risk of both the CGA and the NCGA; the OR (95% CI) was 15.71 (4.23-58.26), and 7.85 (3.12-19.78), respectively (P = 0.00). Finally, the multiple logistic regression analysis showed that the vacA c1 genotype was significantly associated with the age- and sex-adjusted risk for the CGA and the NCGA; the OR (95% CI) was 16.85 (3.83-67.61), and 8.14 (2.83-23.38), respectively (P = 0.00).

Conclusion: The present study showed the determinant role of the H. pylori vacA c1 genotype in the development of both the CGA and the NCGA in Iran. This is the first report of an association of H. pylori genotype with an increased risk of the CGA.

Disclosure of Interest: None declared

P0561 DECREASE OF SERUM TOTAL GHRELIN IN EXTENSIVE ATROPHIC GASTRITIS: COMPARISON WITH PEPSINOGENS IN HISTOLOGICAL REFERENCE

S. E. Bae¹, J. H. Lee¹, H. J. Song¹, H.-Y. Jung¹, K. D. Choi¹, D. H. Kim¹, J. Y. Ahn¹, G. H. Lee¹

¹Gastroenterology, Asan Medical Center, Seoul, Republic of Korea

Contact E-mail Address: space0425@naver.com

Introduction: Ghrelin is mainly secreted from the gastric oxyntic mucosa and the production is impaired in chronic atrophic gastritis. This study aimed to evaluate serum total ghrelin levels according to the extent of histological atrophy, and to compare the performance as a serologic atrophic marker with pepsinogen.

Aims & Methods: Data were analyzed from 154 patients with atrophic gastritis. Histological extent of atrophic gastritis was assessed by three paired biopsies from antrum, corpus lesser, and corpus greater curvature. Fasting serum concentrations of total ghrelin, pepsinogen I, and II were measured with enzyme immunoassay. Regression analysis was performed to evaluate factors associated with serum levels of total ghrelin. The serologic performance was compared with pepsinogen using receiver-operating characteristic curves.

Results: H. pylori infection rate was 85.1% and extensive atrophic gastritis involving corpus greater curvature was found in 24.0%. Serum total ghrelin concentrations were decreased significantly in patients with extensive corpus greater curvature atrophy (median value, 170.4 pg/mL; vs 201.1 pg/mL in patients without corpus greater curvature atrophy; p<0.001), and the levels were correlated with pepsinogen I and pepsinogen I/II ratio. The decrease of serum total ghrelin in corpus greater curvature atrophy was independent of age, gender, body mass index, and H. pylori infection status. Sensitivity and specificity of serum total ghrelin to predict extensive corpus greater curvature atrophy was 56.8% and 78.9%, respectively. The discriminatory ability was similar to pepsinogen I/II ratio (p=0.612) and lower than pepsinogen I (p=0.040).

Conclusion: Serum concentration of total ghrelin is decreased in extensive CGC atrophy. The serologic performance is lower than that of PG I.

Disclosure of Interest: None declared

P0562 ANALYSIS OF DEREGULATED MICRORNAS AND THEIR TARGET GENES IN GASTRIC CANCER

V. Salteniene¹, S. Juzenas¹, J. Kupcinskas², A. Link³, L. Jonaitis², G. Kiudelis², S. Jarmalaite⁴, L. Kupcinskas², P. Malfertheiner³, J. Skieceviciene¹

¹Institute for Digestive Research, ²Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania, ³Department of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University, Magdeburg, Germany, ⁴Division of Human Genome Research Centre, Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania

Contact E-mail Address: violeta.salteniene@gmail.com

Introduction: MicroRNAs (miRNAs) are widely studied non-coding RNAs that modulate gene expression. MiRNAs are deregulated in different tumors including gastric cancer (GC) and have potential diagnostic and prognostic implications. The aim of our study was to determine miRNA profile in GC tissues, followed by evaluation of deregulated miRNAs in plasma of GC patients. Using available databases and bioinformatics methods we also aimed to evaluate potential target genes of confirmed differentially expressed miRNA and validate these findings in GC tissues.

Aims & Methods: The study included 51 GC patients and 51 controls. Initially, we screened miRNA expression profile in 13 tissue samples of GC and 12 normal gastric tissues with TaqMan low density array (TLDA). In the second stage, differentially expressed miRNAs were validated in a replication cohort using qRT-PCR in tissue and plasma samples. Subsequently, we analyzed potential target genes of deregulated miRNAs using bioinformatics approach, determined their expression in GC tissues and performed correlation analysis with targeting miRNAs.

Results: Profiling with TLDA revealed 15 deregulated miRNAs in GC tissues compared to normal gastric mucosa. Replication analysis confirmed that miR-148a-3p, miR-204-5p, miR-223-3p and miR-375 were consistently deregulated in GC tissues. Analysis of GC patients plasma samples showed significant down-regulation of miR-148a-3p, miR-375 and up-regulation of miR-223-3p compared to healthy subjects. Further, using bioinformatic tools we identified targets of replicated miRNAs and performed disease-associated gene enrichment analysis. Ultimately, we evaluated potential target gene BCL2 and DNMT3B expression by qRT-PCR in GC tissue, which correlated with targeting miRNA expression.

Conclusion: Our study revealed miRNA profile in GC tissues and showed that miR-148a-3p, miR-223-3p and miR-375 are deregulated in GC plasma samples. Target gene analysis demonstrated that BCL2 and DNMT3B expression in GC tissue correlated with their targeting miRNA expression.

Disclosure of Interest: None declared

MONDAY, OCTOBER 26, 2015   09:00-17:00

SMALL INTESTINAL I – HALL 7__________

P0563 INTESTINAL EPITHELIAL BARRIER DYSFUNCTION IN PATIENTS WITH CHRONIC INTESTINAL PSEUDO-OBSTRUCTION

E. Boschetti¹², A. Accarino³, A. Gori¹, C. Malagelada³, F. Giancola¹, V. Tugnoli², E. Bonora¹, F. Bianco¹, G. Barbara¹, F. Azpiroz³, J. R. Malagelada³, V. Stanghellini¹, R. De Giorgio¹

¹Department of Medical and Surgical Sciences, ²Biomedical and neuro-motor science, University of Bologna Italy, Bologna, Italy, ³Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain

Contact E-mail Address: elisa.boschetti@unibo.it

Introduction: Chronic intestinal pseudo-obstruction (CIPO) is a rare condition characterized by gastrointestinal (GI) impairment that is so severe to cause a clinical picture suggestive of a mechanical obstruction in the absence of any occlusion. Although degenerative or inflammatory neuro-interstitial cells of Cajal (ICC)-muscular abnormalities are the main pathogenetic mechanisms underlying gut dysfunction, other factors, i.e. intestinal epithelial barrier (IEB) abnormalities, may represent the initial insult contributing to symptoms and clinical manifestations

Aims & Methods: The present study aims to assess the expression of occludin and zonula occludens-1 (ZO-1), two major components of tight junctions (TJs), as markers of IEB integrity in patients with CIPO. A number of n=26 clinically and histopathologically well characterized CIPO pts (15 F; age range: 16 - 75 yrs) were studied. CIPO cases were subdivided according to the histopathological analysis (IHC) in 3 groups: A) apparently normal n=7; B) inflamed n=8; C) degenerative n=10. Patients (n=8; 3 F, age range: 48 - 73 yrs) undergoing elective surgery for uncomplicated neoplastic diseases served as controls. CIPO and control jejunal full thickness biopsies were processed to assess occludin and ZO-1 mRNA and protein expression using q-PCR and WB.

Results: Compared to controls, total occludin protein showed a marked decrease in CIPO pts (P < 0.05); also, a tendency to a decreased occludin mRNA expression was found in CIPO vs. controls. Moreover, occludin oligomers, an index of occludin assembly in rafts TJs, were detected only in 19% of CIPO pts while all controls showed normal oligomerization. ZO-1 protein and mRNA expression did not change in CIPO vs controls. Interestingly, the three histologically identified groups of CIPO showed a selective reduction of only one of the two analyzed components. Specifically, in group A and B occludin expression decreased, while in group C only ZO-1 content decreased.

Conclusion: IEB integrity was altered in patients with CIPO as identified by the reduction of at least one of the TJ components. Moreover, the abnormal occludin oligomerization is indicative of TJ dysfunction, which increases the possibility of noxious agents passing through the intestinal wall in these patients. A better knowledge of IEB altered molecular mechanisms is expected to be translated in targeted therapeutic interventions.

Disclosure of Interest: None declared

P0564 LISTERIA MONOCYTOGENES AFFECTS SEROTONIN TRANSPORTER ACTIVITY AND EXPRESSION IN HUMAN INTESTINAL EPITHELIAL CELLS BY TLR10 ACTIVATION

E. Latorre¹, A. Pradilla¹, B. Chueca², R. Pagán², E. Layunta¹, J. E. Mesonero¹, A. I. Alcalde¹

¹Pharmacology and Physiology, ²Animal Production and Food Science, Zaragoza University, Zaragoza, Spain

Contact E-mail Address: latorre.duque@gmail.com

Introduction: Serotonin (5-HT) is a neuromodulator mainly synthesized in the intestinal epithelium. 5-HT regulates the whole intestinal physiology and it has been shown to be essential in intestinal homeostasis. In fact the excess of extracellular 5-HT has been described to contribute to intestinal inflammation. 5-HT availability is in part mediated by the serotonin transporter (SERT), which is responsible for the 5-HT reuptake inside the enterocytes. Recent results have demonstrated that bacteria resident in the intestinal lumen may affect intestinal pathophysiology by acting on the serotoninergic system. This effect is in part carried out through the activation of Toll-like receptors (TLRs) which regulates SERT in the intestinal epithelium. Listeria monocytogenes is a Gram-positive bacteria that causes in humans a serious infection (listeriosis) mainly through the consumption of ready-to-eat foods. Following ingestion, L. monocytogenes has been described to cross the intestinal epithelium and to invade intestinal epithelial cells. However, the effect of L. monocytogenes on intestinal epithelium activity remains unknown.

Aims & Methods: 5-HT has been shown to be an essential regulator of the intestinal physiology. 5-HT availability has been shown to be modulated by the activity of SERT expressed in intestinal epithelial cells. Therefore, the aim of the present study was to analyze whether the pathogen L. monocytogenes affects the intestinal epithelial activity, by focusing on the analysis of SERT in intestinal epithelial cells. In this study human enterocyte-like Caco-2/TC7 cell line was used. These cells express SERT and TLRs. Caco-2/TC7 cells were treated with L. monocytogenes, and 5-HT uptake by SERT and transepithelial resistance (TER) were measured. The molecular expression of SERT, TLR2 and TLR10 were analyzed by measuring both, mRNA levels by RT-qPCR, and protein expression by western blotting.

Results: L. monocytogenes did not appear to affect TER in the Caco-2/TC7 cells, but the treatment showed to inhibit 5-HT uptake by reducing SERT expression in the cells. However, L. monocytogenes inactivated by heat or by pulsed electric fields did not affect SERT activity. Moreover, factors secreted by this bacteria did not seem to be involved in effects on SERT. TLR2 expression in Caco-2/TC7 cells resulted down-regulated by L. monocytogenes, however, TLR10 expression appeared to be increased. In this context, TLR10 seemed to be involved in the effect of L. monocytogenes on SERT, since the effect disappears by treating the cells with TLR10 specific antibody.

Conclusion: L. monocytogenes, a known powerful pathogen bacteria, may induce an alteration of the intestinal homeostasis by inhibiting SERT function and expression. This effect might cause an increase in the level of extracellular 5-HT and, thereby, might contribute to an intestinal proinflammatory effect. Our results demonstrate that L. monocytogenes requires be alive to alter SERT, and they show for the first time that this effect may be mediated by TLR10. Moreover, L. monocytogenes seemed to yield TLR2 and TLR10 transcriptional effects in intestinal epithelial cells.

Disclosure of Interest: None declared

P0565 MAGNETIC RESONANCE IMAGING-QUANTIFIED SMALL BOWEL MOTILITY IS A SENSITIVE MARKER OF RESPONSE TO ANTI-TNFA THERAPY IN CROHN’S DISEASE

A. Menys¹, A. Plumb¹, E. Russo², D. Prezzi¹, G. Bhatnagar¹, R. Vega³, S. Halligan¹, T. Orchard⁴, S. A. Taylor¹

¹Centre for Medical Imaging, UCL, ²Department of Gastroenterology, Imperial, ³Gastroenterology, UCLH, ⁴Gastroenterology, Imperial, London, United Kingdom

Contact E-mail Address: alex.menys.09@ucl.ac.uk

Introduction: Dynamic imaging in Magnetic Resonance Enterography (MRE) is increasingly used as a non-invasive method of assessing small bowel (SB) motility. The purpose of this study was to determine if improvements in segmental SB motility can detect clinical response to anti-TNFα therapy, both after induction therapy and longer term.

Aims & Methods: Patient demographics: 46 patients underwent MRE pre- and post-treatment with anti-TNFα agents:

- 11 recruited prospectively (imaged after a median of 12 weeks of treatment, median age 40 years (range 22 to 57), 6 Male, median disease duration 4 years (range 1 to 30)) and,

- 35 identified retrospectively (median=55 weeks of treatment, median age 23 years (range 15 to 65), 21 Male, median disease duration 16 years (range 6 to 53)).

Scanning protocol: Patients in both groups were prepared with 1-2L oral contrast (2% mannitol) depending on their tolerance. Dynamic motility scans were acquired using a 3T Siemens (prospective cohort) and across 1.5T Siemens and 3T Philips scanners (retrospective cohort). Temporal and spatial resolution across all scanners was standardized prior to analysis.

Motility Analysis: Data was processed using a validated optic-flow registration technique to provide quantitative motility maps describing the deformation from bowel wall motion. A consultant radiologist (4 years MRE experience) assessed the two MRI time points and placed a region of interest over diseased small bowel (identified on the basis of mural thickening), blinded to other imaging sequences. The study coordinator (4 years experience with MRE) performed the quantitative analysis.

Therapeutic response: Response was defined using a composite of all available clinical data for the retrospective group; and by a ≥3 point drop in the Harvey-Bradshaw Index for the prospective group.

Statistical analysis: The small bowel motility score took the form of a numerical arbitrary unit value. The higher the score, the greater motility with values typically occurring between 0 (no motility) and 0.6 (high motility). The percentage change in motility score between the two scans was calculated and compared between responders and non-responders using the Mann-Whitney U test. Receiver-operating characteristic (ROC) curves were calculated to assess the sensitivity and specificity of motility as a predicator of therapeutic response.

Results: Anti-TNFα responders had significantly greater improvements in motility (median change=68.6% increase from baseline) than non-responders (median change=25% reduction, p < 0.001).

Improved MRI-measured motility was 89.7% (95%CI 73.6-96.4%) and 82.5% specific (95%CI 59.0-93.8%) for response to anti-TNFα treatment, in both the prospective (Sn:85.7%; Sp:100%) and retrospective groups (Sn: 90.9%; Sp:76.9%).

The area under the ROC curve for motility changes to discriminate responders from non-responders was 87.9% (95%CI:77.2-98.6%).

Conclusion: Improved MRI-measured SB motility accurately detects response to anti-TNFα therapy for CD, even as early as 12 weeks. MRI may permit early identification of response/non-response to anti-TNFα agents, allowing personalized treatment regimes.

Disclosure of Interest: A. Menys Shareholder: Motilent Ltd, Directorship(s): Motilent Ltd, A. Plumb: None declared, E. Russo: None declared, D. Prezzi: None declared, G. Bhatnagar: None declared, R. Vega: None declared, S. Halligan: None declared, T. Orchard: None declared, S. Taylor: None declared

P0566 EPSILON GERM LINE AND REGULATORS OF IGE-DEPENDENT INFLAMMATION ARE UPREGULATED IN THE DUODENAL MUCOSA OF ATOPIC BUT NOT IN NON-CELIAC GLUTEN SENSITIVITY PATIENTS: A PRELIMINARY REPORT

A. Sapone¹, V. Casolaro², S. Senger³, P. Esposito⁴, M. I. Russo⁴, D. Leffler⁵, A. Pezzullo⁴, P. Schettino⁴, G. Riegler⁴, L. de Magistris⁴, A. Fasano³

¹BIDMC, Boston, United States, ²University of salerno, Salerno, Italy, ³Mucosal Immunology and Biology Research Center, Boston, United States, ⁴Second University of Naples, Napoli, ⁵BIDMC, Boston, Italy

Contact E-mail Address: annasapone@yahoo.it

Introduction: Gluten-related disorders are activated by the ingestion of gluten-containing grains by individuals with a genetic and/or immunologic predisposition to these conditions. The best-known diseases, wheat allergy (WA) and celiac disease (CD), are mediated by the adaptive immune system. In wheat allergy, immunoglobulin E (IgE) is cross-linked by repeat sequences in gluten peptides (e.g. Ser-Gln-Gln-Gln-(Gln-)Pro-Pro-Phe), inducing the release of immune mediators such as histamine from basophils and mast cells. In contrast, CD has characteristics of an autoimmune disorder. Besides CD and WA, reactions have been reported to gluten-containing grains that involved neither allergic nor autoimmune mechanisms. These are generally termed NCGS. Given the uncertainties about this clinical entity and the lack of diagnostic biomarkers, several reports concluded that NCGS could be defined as a clinical entity induced by the ingestion of gluten-containing grains leading to intestinal and/or extra-intestinal symptoms that resolve once gluten-containing grains are eliminated from the diet, provided that CD and WA have been ruled out. One of the most controversial and highly debated discussions about NCGS concerns the role of gluten in causing NCGS and the hypothesis that some NCGS patients might also have a form of WA that is not detected with conventional serologic or skin tests.

Aims & Methods

Aim: To investigate the local IgE response in the duodenal mucosa of NCGS patients.

Methods: The intestinal mucosa from 7 healthy controls (HC), 13 active CD, 8 active NCGS, and 4 atopic patients was analyzed for the expression of genes involved in class switch recombination to IgE and IgG subclasses, such as ϵ germline transcripts (GLT) and activation-induced cytidine deaminase (AICD), and established regulators of IgE production and IgE-dependent inflammation, such as IL-4, IL-5, and IL-13, by real-time RT-PCR.

Results: The level of ϵ GLT in the mucosa of NCGS patients was significantly lower relative to atopic patients (p=0.009). IL-4, IL-5, and IL-13 mRNA expression was also significantly reduced in NCGS patients ( p < 0.05), whereas GLT expression for IgG1, IgG3, IgG4, and IgM was similar in all groups of patients. Finally, the level of the B-cell activation marker AICD was also significantly reduced in NCGS compared to the atopic mucosa (p=0.04).

Conclusion: These findings support and extend the idea that the three gluten-associated disorders, CD, NCGS and WA, are different clinical and pathogenetic entities, whereby NCGS is a condition prevalently associated with wheat-induced activation of the innate, rather than adaptive, immune response.

Disclosure of Interest: None declared

P0567 INCREASED INTESTINAL MUCOSAL PRODUCTION OF IMMUNOGLOBULIN G IN DIARRHEA-PREDOMINANT IRRITABLE BOWEL SYNDROME

C. Pardo-Camacho¹, A. M. González-Castro¹, B. Lobo¹, C. Alonso-Cotoner¹², M. Fortea¹, M. Casado-Bedmar¹, B. Rodiño-Janeiro¹, F. Azpiroz¹², J. Santos¹², M. Vicario¹²

¹Neuro-immuno-gastroenterology Laboratory, Digestive Diseases Research Unit, Department of Gastroenterology, Vall d’Hebron Institut de Recerca & Hospital Universitari Vall d’Hebron, ²Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd, Barcelona, Spain

Contact E-mail Address: maria.vicario@vhir.org

Introduction: Enhanced mucosal humoral immunity has recently been implicated in the pathophysiology of diarrhea-prone irritable bowel syndrome (IBS-D). Intestinal barrier dysfunction is associated with mucosal immune activation, likely induced by luminal antigens, however little is known about the antibody response in the intestinal mucosa in functional bowel disorders.

Aims & Methods: We aimed at characterizing the isotype of mucosal immunoglobulins (Ig) being produced in IBS-D. Mucosal jejunal biopsies, stool and blood samples were obtained from healthy volunteers (H; n=18) and age-matched naïve participants meeting diarrhea-IBS Rome III criteria (IBS-D; n=20). Bowel movements, stool consistency and abdominal pain were monitored in the prior 10 days to the biopsy. The number and ultrastructure of plasma cells in the jejunal mucosa was determined by transmission electron microscopy, and mucosal IgG⁺ cells were quantifed by immunofluorescence. Stool and blood samples were assayed for IgG, IgM and IgA quantification by ELISA technique.

Results: The number of plasma cells was higher in IBS-D patients (IBS-D: 1,257 ± 966) respect to H participants (H: 266 ± 199; P < 0.05). In both groups, plasma cells displayed signs of activation and Ig production such as massive amount of endoplasmic reticulum and enlarged cisternae, however the presence of plasma cell clusters was more abundant in the IBS-D group. The number of IgG⁺ cells was higher in the IBS-D group (H: 240 ± 149; IBS-D: 650 ± 150 cells/mm²; P < 0.05). The amount of IgG in feces was also higher in the IBS-D group (H: 165 [31-1,767]; IBS-D: 553 [76-2,291] ng/mg protein P < 0.05), as well as IgA concentration, the later not reaching statistical significance (H: 580 [70-3,565]; IBS-D: 1,455 [201-11,056] µg/mg protein, P=0.059). Differences in mucosal Ig were not detected in systemic circulation. In IBS-D, the concentration of IgG in feces positively correlated with abdominal pain (r²=0.538; P < 0.05).

Conclusion: IgG production rises as a distinctive marker of mucosal immune activity in association with abdominal pain in IBS-D. Studies aimed at determining IgG subtype and antigens eliciting such responses warrant further investigation.

Disclosure of Interest: None declared

P0568 NOD1 AND NOD2 INTERACT WITH SEROTONIN TRANSPORTER AND TOLL-LIKE RECEPTORS IN INTESTINAL EPITHELIAL CELLS. ANALYSIS IN INTESTINAL TRACT FROM MICE COLITIS MODEL

E. Layunta¹, E. Latorre¹, L. Grasa¹, M. Castro¹, J. Pardo², F. Gomollón³, A. I. Alcalde¹, J. E. Mesonero¹

¹Pharmacology and Physiology, ²Biochemistry and Molecular and Cellular Biology, University of Zaragoza, ³Lozano Blesa Clinic Hospital, Zaragoza, Spain

Contact E-mail Address: elena.layunta@unizar.es

Introduction: The intestinal epithelium presents an innate immune system and a serotoninergic system, which interact to contribute to the intestinal homeostasis. The deregulation of this interaction has been described to be involved in intestinal inflammation. Intestinal innate immune system recognizes the microbiota through host recognition receptors, such as Toll-like (TLR) and Nod-like (NOD). These receptors trigger host responses to develop either a tolerant or a defense effect. Inflammatory Bowel Diseases (IBDs) are the result of an inappropriate response to the microbiota, in part mediated by deregulation of NODs and TLRs. Additionally intestinal serotoninergic activity mediated by an increase of extracellular serotonin (5-HT) has been observed to contribute to IBDs. Serotonin transporter (SERT) modulates intestinal 5-HT availability, therefore SERT activity has been considered as an essential tool to be analyzed in intestinal inflammatory processes.

Aims & Methods: The aim of present study was to analyze whether NOD1 and NOD2 alter SERT expression and activity. Furthermore, we aimed to study a possible cross-talk between NOD1 and NOD2, TLR2 and TLR4. Finally, we have assessed NOD1, NOD2, TLR2, TLR4 and SERT expression in a mice colitis model. The human enterocyte-like cell line Caco-2/TC7 was used. Ileum and colon from C57BL6 mice wild type (WT) and Dextran Sodium Sulphate treated (DSS colitis model) were also analyzed. SERT activity was determined by 5-HT uptake measurement. SERT, NOD1, NOD2, TLR2 and TLR4 mRNA were measured by RT-qPCR. Protein expression of SERT, NOD1 and NOD2 were quantified by western blot.

Results: NOD1 and NOD2 activation decreased SERT activity and expression (mRNA and protein) in Caco-2 cells. In this context, TLR2 activation showed to increase both NOD1 and NOD2 mRNA levels, while NOD1 and NOD2 protein expression did not seem to be affected. On the contrary, TLR4 activation showed to decrease NOD1 and NOD2 mRNA and NOD1 protein level with no effect on NOD2 protein level. In relation to the analysis of NODs and TLRs mRNA in mice intestinal tract, the results have shown that in ileum of DSS mice, NOD1, NOD2, TLR2 and TLR4 did not seem to be modified compared with WT. In contrast, in colon of DSS mice, NOD2 and TLR2 mRNA resulted increased, whereas NOD1 and TLR4 mRNA did not show to be affected. Analysis of SERT expression in mice intestine has shown that mRNA and protein expression resulted decreased in both ileum and colon of DSS mice compared with WT.

Conclusion: NOD1 and NOD2 activation seems to regulate intestinal 5-HT level by acting on SERT in the intestinal epithelium. Moreover, the expression of NOD1 and NOD2 in intestinal epithelial cells may be regulated by TLR2 and TLR4 activation, which confirms a cross-interaction between several components of the innate immunity system in intestinal epithelium. Finally, both innate immune and serotoninergic system resulted altered in colitis intestinal tract, thus suggesting a synergy between both systems in intestinal inflammatory processes.

Disclosure of Interest: None declared

P0569 DECREASED PROINFLAMMATORY PROFILE AND INCREASED CORTICOTROPIN RELEASING FACTOR IN MUCOSAL EOSINOPHILS IN ASSOCIATION WITH CLINICAL MANIFESTATIONS DIARRHEA-PRONE IRRITABLE BOWEL SYNDROME

E. Salvo-Romero¹, C. Marinez², B. Lobo¹, M. Pigrau¹, M. Casado-Bedmar¹, A. Sánchez-Chardi³, A. M. González-Castro¹, B. Rodiño-Janeiro¹, M. Fortea¹, C. Pardo-Camacho¹, F. Azpiroz¹⁴, C. Alonso-Cotoner¹⁴, J. Santos¹⁴, M. Vicario¹⁴

¹Neuro-immuno-gastroenterology Laboratory, Digestive Diseases Research Unit, Department of Gastroenterology, Institut de Recerca Vall d’Hebron & Hospital Universitari Vall d’Hebron, Barcelona, Spain, ²Department of Human Molecular Genetics, Institute of Human Genetics, Univeristy of Heidelberg, Heildelberg, Germany, ³Servei de Microscopia, Facultat de Ciències, Campus de la Universitat Autònoma de Barcelona, ⁴Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd, Barcelona, Spain

Contact E-mail Address: eloisasalvo1@gmail.com

Introduction: Irritable bowel syndrome (IBS) is characterized by psychological stress and altered intestinal barrier function. Peripheral corticotropin-releasing factor (CRF) and neuropetides such as Substance P (SP) are involved in stress-induced gut dysfunction and CRF has been related to mucosal eosinophils. However, the role of eosinophils in IBS remains unknown.

Aims & Methods: To identify the role of mucosal eosinophils in IBS-D, and to evaluate the mechanisms underlying the stress response using an eosinophil in vitro model.

Methods: Healthy (H) subjects (n=18) and age-matched, naïve participants fulfilling diarrhea-prone IBS (IBS-D) Rome III (n=23) were included. Jejunal biopsies were obtained by Watson's capsule in all participants. Mucosal eosinophil ultrastructure, CRF inmunolabelling, activation and secretory activity, were evaluated by transmission electron microscopy or gene expression (microarray and quantitative RT-PCR). Psychological stress, abdominal pain, the number of bowel movements per day, and the stool form were obtained in all participants. The eosinophil cell line 15HL60 was differenciated and stimulated with SP, and secretory activity and CRF content were assessed by RT-PCR, immunofluorescence.

Results: Microarray and IPA analysis revealed eosinophil activity (P < 0.0001) in IBS vs H. Array validation revealed decreased eotaxin, EDN and ECP gene expression, but increased synaptosomal-associated protein SNAP-23 (P<0.05) in IBS-D compared to H. CRF was identified only in cytoplasmic eosinophil granules, with increased content in IBS-D (IBS-D=7,3 [2,99;11,4]; H=1,9 [0,75; 4,10] particles/granule; P < 0.01). Notably, the amount of CRF significantly correlated with baseline level of stress (r_s=0.70; P=0.018), depression (r=0.61; P=0.037), the number of bowel movements (r_s=0.78; P=0.007) and the stool consistency (r_s=0.67; P=0.027). In vitro, eosinophils expressed NKR1 and responded to SP by relocation of SNAP-23, VAMP2 and CRH from the cytoplasm to the plasma membrane, without changes in gene expression profile of pro-inflamatory proteins.

Conclusion: CRF is stored in jejunal mucosal eosinophils and its increase correlates with clinical symptoms in IBS-D. Similarity between mucosal eosinophils and in vitro response to SP, suggests eosinophil contribution to IBS through neuroimmune mechanisms.

Disclosure of Interest: None declared

P0570 GLIADIN EFFECT ON THE OXIDATIVE BALANCE AND DNA DAMAGE IN CACO2 CELL LINE

E. Monguzzi¹, L. Marabini², L. Roncoroni³, F. Ferretti¹, D. Conte¹, L. Elli³

¹Department of Pathophysiology and Transplantation, ²Department of Pharmacological and Biomolecular Sciences, University of Milan, ³Gastroenterology and Endoscopy Unit, IRCCS Fondazione Cà Granda Ospedale maggiore Policlinico, Milan, Italy

Contact E-mail Address: erika.monguzzi@gmail.com

Introduction: Recently, gluten and gliadin have been identified as a key environmental factor in different human disorders ( celiac disease, food allergies and non celiac gluten sensitivity).

They induce different biological alterations into the cell. In particular, the gluten-cell interaction increases the expression and the cellular content of transglutaminase type 2 enzyme (TG2) and altering the pro-oxidant–antioxidant balance in the intestinal mucosa, accompanied by ROS overproduction.

Aims & Methods: Evaluation of gliadin effect on oxidative/reductive balance and assessment of the possible genotoxic damage caused by free radicals

Caco2 cells were treated with gliadin (digested according to the method: S. Friis, Gut 1992; 33:1487-1492) at different concentrations (range 15 µg/mL-1mg/mL) for 24h. We investigated: i) cytotoxicity (MTT test); ii) oxidative stress through the evaluation of reactive oxygen species (ROS, flow cytometry with DCFDA); iii) DNA damage by means of comet test, to detect single, double strand breaks and alkali labile sites; iv) TG2 activity in different cellular compartment (colorimetric assay).

Results: After 24h of gliadin treatment we observed a decrease in cell viability of about 50% at the dose of 1mg/mL. ROS levels showed a 30% increase also using low gliadin doses (30µg/mL). A DNA damage was observed at comet assay as demonstrated by an increase of tail moment particularly visible at 1mg/mL of gliadin concentration. Following the doses indicated by ROS, the activity of TG2 was increased after gliadin treatment (30µg/mL) with a translocation from the cytoplasm to the nucleus, suggesting an apoptotic phenomenon.

Conclusion: Gliadin induces a cellular oxidative stress. Moreover, our findings demonstrate a DNA damage and a TG2 activity translocation from the cytoplasm to the nucleus.

Disclosure of Interest: None declared

P0571 THE DEPLETION OF MURINE MICROBIOTA BY BACITRACIN AND NEOMYCIN REDUCES THE INTESTINAL PERMEABILITY BY INCREASING THE LEVELS OF ZO-1, JAM-A AND OCCLUDIN

L. Grasa¹, R. Nevado¹, R. Forcén¹, E. Layunta¹, E. Latorre¹, A. I. Alcalde¹, M. D. Murillo¹

¹Pharmacology and Physiology, University of Zaragoza, Zaragoza, Spain

Contact E-mail Address: lgralo@unizar.es

Introduction: Oral bacitracin has been used for the treatment of Clostridium difficile-associated diarrhoea and colitis. Oral neomycin is indicated for suppression of intestinal microbiota in patients undergoing colorectal surgery. Antibiotics may alter the intestinal microbiota and affect the intestinal permeability. The intestinal epithelial permeability is regulated by the tight junctions (TJs) proteins. The TJs complex consists of transmembrane (occludin, junctional adhesion molecule (JAM), claudins) and intracellular scaffold (ZO-1) proteins¹.

Aims & Methods: The aim was to investigate the effects of the oral administration of bacitracin and neomycin on murine intestinal permeability and the expression of TJs proteins.

Female C57BL/10 mice of 5-7 weeks old were divided into two groups: control and treated with antibiotics. Mice were gavaged for 7 consecutive days with water (controls) or a combination of antibiotics (bacitracin 20 mg and neomycin 20 mg) per mouse and day (treated mice). This combination of antibiotics has been shown to deplete the intestinal microbiota². In vivo paracellular permeability assay to assess barrier function was performed using an FITC-labelled dextran method. Mice were gavaged with 60 mg per 100 g body weight of FITC-dextran and at 4 h serum samples were obtained. Fluorescence intensity was measured (excitation, 485 nm; emission, 535 nm) and FITC-dextran concentrations were determined. TJs protein gene expression (mRNA) was determined in ileum and colon by quantitative RT-PCR.

Results: Control mice showed levels of FITC-dextran of 378.45 ± 60.20 ng mL^-1 of blood. In comparison, there was a reduction to the half in FITC-dextran levels in antibiotics treated mice (208.09 ± 25.84 ng mL^-1), suggesting increased barrier function in these mice. The treatment with bacitracin and neomycin increased the expression of ZO-1, JAM-A and occludin in mice ileum and colon. However, the treatment with these antibiotics reduced the levels of claudins-3, 4 and 7 in ileum, but increased the levels of claudins-3 and 4 in colon.

Conclusion: Microbiota may regulate the intestinal permeability. The oral treatment with bacitracin and neomycin enhances the barrier function by increasing the levels of the tight junction proteins ZO-1, JAM-A and occludin.

Disclosure of Interest: None declared

P0572 NON-INVASIVE MONITORING OF REGIONAL TISSUE OXYGENATION IN NEWBORN USING NEAR-INFRARED SPECTROSCOPY

L. Olariu¹, G. Olariu², S. Olariu³, O. Belei¹, O. Marginean¹

¹First Pediatric Clinic, University of Medicine and Pharmacy Victor Babes, Timisoara, Romania, Timiosara, ²Neonatology, Timisoara Municipal Hospital, Timisoara, ³Neonatology Department, Timisoara Municipal Hospital, Timiosara, Romania

Contact E-mail Address: tunealaura@yahoo.com

Introduction: Near-infrared spectroscopy (NIRS) is a noninvasive method for monitoring in real time regional tissue oxygenation status. NIRS has the ability to continuously and simultaneously monitor tissue perfusion in various organs, without interrupting daily care. Research has demonstrated its usefulness in monitoring cerebral, intestinal and renal perfusion, in detection of potential ischemic episodes.

Aims & Methods: NIRS was used in comparation, through somatic regional oxygen saturation (rSO2S), cerebral saturation(rSO2C) and cerebro- somatic oxygenation ratio (ROCS) in a group of 30 newborns with gestational age(GA) between 24-39 weeks, birth weight 600- 3100 grams, from day 3 until day 21 of life, over a 1-5 day, period required for causal diagnosis, in which we clinically presumed a decrease in mesenteric blood flow. The group included 12 newborns with ulceronecrotic enterocolitis (NEC), 6 newborns with intrauterine growth retardation (IUGR), 6 newborns with congenital heart malformation (CHM) and 6 infants with sepsis. rSO2-S and ROCS were compared with each other to determine which of the two parameters are faithful for detecting changes in tissue perfusion. To verify statistical hypothesis which states that there are significant differences regarding rSO2S value and ROCS depending on the type of the disease were used ANOVA statistical tests, Bonferroni option and Pearson correlation

Results: In the NEC group the rSO2S average was 40.37 compared with 44.94 for CHM group, 51.86 in IUGR group and 53.08 for the sepsis group. The ROCS average achieved was 0.59 for NEC, 0.68 in CHM group, 0.97 in sepsis group and 0.73 for IUGR. No statistically significant differences were found for rSO2S (F = 1.69, p = 0.18, p?0.05) inside the group and between groups values but were significant for ROCS (F = 2.82, p = 0, 04, p <0.05).

Conclusion: The study shows that continuous noninvasive monitoring with NIRS technology can show that impaired intestinal perfusion increases with decreasing GA. Decreases of the two parameters are influenced by GA (rSO2S: p = 0.008; ROCS: p = 0.03). The lowest values of intestinal perfusion are in NEC (rSO2 = 40.37, ROCS = 0.59), followed by CHM (rSO2S = 44.94, ROCS = 0.68), IUGR (rSO2S = 51.86, ROCS = 0.73) and sepsis (rSO2S = 53.08, ROSC = 0.97). rSO2S value is less statistically significant (F = 2.82, p = 0.18) compared with ROCS (F = 2 82 p = 0.04) in patients with NEC compared to those with CHM, sepsis or IUGR.

ROCS is the most accurate parameter in determining intestinal perfusion changes and the use of NIRS remains a very good method for early detection of lower intestinal perfusion in various diseases.

Disclosure of Interest: None declared

P0573 RIFAXIMIN PREVENTS ENTERIC BACTERIA ALTERATIONS AND INFLAMMATION IN A RAT MODEL OF DICLOFENAC-INDUCED ENTEROPATHY

R. Colucci¹, E. Ghelardi², E. Tirotta¹, E. Piccoli², D. Sacco¹, L. Antonioli¹, M. Fornai¹, C. Renzulli³, C. Pellegrini¹, C. Blandizzi¹, C. Scarpignato⁴

¹Dept. Clinical and Experimental Medicine, ²Dept. Translational Research and NTMS, University of Pisa, Pisa, ³Research and Development Division, Alfa Wassermann SpA, Bologna, ⁴Dept. Clinical and Experimental Medicine, University of Parma, Parma, Italy

Contact E-mail Address: r.colucci@med.unipi.it

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs), besides exerting detrimental effects on the upper digestive tract, can also damage the small and large intestine. Although the underlying mechanisms remain unclear, there is evidence that enteric bacteria could play a prominent role. In particular, NSAIDs increase mucosal permeability, thus facilitating the entrance and action of bacteria, which trigger the inflammatory cascade via activation of Toll-like receptors (TLRs).

Aims & Methods: The present study examined the effects of rifaximin, a poorly absorbed antibiotic, on enteric bacterial load and composition as well as small bowel inflammatory responses in a rat model of diclofenac-induced enteropathy. Enteropathy was induced in male rats (40-weeks old) by intragastric diclofenac administration (4 mg/kg BID) for 14 days. Control animals received drug vehicle (0.3 ml of 1% methylcellulose). A group of rats received Rifaximin-EIR (enteric coated microgranules of rifaximin), (50 mg/kg BID), 1 hour before diclofenac (n=6-7 per group). At the end of treatments, feces were collected to quantify calprotectin content by ELISA. Ileum was excised and processed for the evaluation of: 1) tissue myeloperoxidase levels (as an index of neutrophil infiltration); 2) bacterial total load and quantitative analysis of strains, via 16S real-time PCR; 3) expression of TLR-2/4 and activation of downstream signaling as phosphorylated nuclear factor kB subunit p65 (NF-kB p65) and myeloid-differentiation primary response-gene 88 (MyD88), by Western blot.

Results: In control animals, myeloperoxidase and calprotectin levels were 6.0 ± 1.1 ng/mg and 2.5 ± 0.2 ng/mg, respectively. These parameters were significantly increased (by 290% and 52%) in diclofenac-treated rats. Ileal specimens from control animals were found to contain a total bacterial load of 4.66 ± 1.01x10¹⁰. In particular, the Bacteroidetes phylum was 0.14 ± 0.05x10¹⁰ and the Firmicutes phylum was 0.26 ± 0.03x10¹⁰. All these bacterial loads increased after treatment with diclofenac. The expression of TLR-2/4, NF-kB p65 and MyD88 in diclofenac-treated animals was higher, as compared with control animals (+104%, +23%, +147% and +71%, respectively). In rats treated with diclofenac plus Rifaximin-EIR, myeloperoxidase and calprotectin levels were lower in comparison with diclofenac alone (-74% and -89%, respectively ). In this setting, the bacterial total load decreased by 88%, with a significant reduction of Bacteroidetes and Firmicutes, while the increased expression levels of TLR-2/4, NF-kB p65 and MyD88 returned towards control values.

Conclusion: In the small bowel, treatment with diclofenac leads to quantitative and qualitative alterations of enteric bacteria that are associated with increased expression/activation of TLR-2/4 and consequent tissue inflammation. Under these conditions, Rifaximin-EIR counteracts the bacterial changes and promotes a normalization of related inflammatory responses. These peculiar pharmacological actions of rifaximin may represent the underlying mechanism(s) of its preventive activity against NSAID-induced intestinal damage, recently shown in rats¹ and humans² in our Institutions.

Disclosure of Interest: R. Colucci: None declared, E. Ghelardi: None declared, E. Tirotta: None declared, E. Piccoli: None declared, D. Sacco: None declared, L. Antonioli: None declared, M. Fornai: None declared, C. Renzulli Conflict with: employ of Alfa Wassermann, C. Pellegrini: None declared, C. Blandizzi Lecture fee(s): Alfa Wassermann, C. Scarpignato Consultancy: Alfa Wassermann

P0574 WHEAT ALPHA-AMYLASE/TRYPSIN INHIBITORS (ATIS) EXACERBATE AUTOIMMUNE ENCEPHALOPATHY IN MICE

V. F. Zevallos¹, N. Yogev², A. Nikolaev², A. Waisman², D. Schuppan¹

¹Institute of Translational Immunology, ²Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

Contact E-mail Address: zevallos@uni-mainz.de

Introduction: We identified wheat alpha-amylase/trypsin inhibitors (ATIs) as main activators of innate immunity by engaging the toll like receptor 4 (TLR4)-MD2-CD14 complex in cells of the mononuclear phagocyte system. ATIs play a fundamental role in the pathogenesis of celiac disease (CD) and other autoimmune diseases.

Aims & Methods: The aim of this study is to evaluate the effects of dietary ATIs on murine experimental autoimmune encephalitis (EAE), a preclinical model of human multiple sclerosis (MS). Female mice (C57BL/6) were fed with a gluten/ATI-free diet for 4 weeks and thereafter EAE was induced by injecting 50 μg of MOG 35-55 peptide emulsified in CFA and supplemented with heat-inactivated M. tuberculosis (day 0) in the tail base and 200 ng pertussis toxin i.p. on day 0 and 2. On day 0 the protein (casein) adjusted diet was continued as follows: 1) gluten/ATI-free; 2) 25% gluten (ATIs equivalent to the human wheat based diet); 3) 25% gluten de-enriched of ATIs; 4) purified ATIs. Mice were monitored daily for clinical signs of EAE (graded on a scale from 0 to 5) and euthanized at the peak of EAE for molecular, histological and immunohistological studies on gut, brain, spinal cord, lymph nodes and spleen. In addition, lymphoid organs were harvested for analysis of immune cell specific markers using flow cytometry.

Results: Mice on a gluten/ATI-free diet and on a diet containing 25% gluten de-enriched of ATIs had a significant lower clinical score compared to animals on a diet containing 25% gluten (and ATIs) or purified ATIs. We also observed that both intestinal and CNS-infiltrating total and encephalitogenic T cells (CD4⁺IFNg⁺IL-17⁺) were significantly increased in the ATI fed groups, paralleled by significantly increased tissue and circulating levels of MCP-1, IL-8 and IL-6.

Conclusion: 1) Nutritional wheat ATIs exacerbate EAE in mice; 2) a gluten/ATI-free diet ameliorates the course of EAE; 3) gluten depleted from ATIs fails to exacerbate the development of EAE, indicating that ATIs are important nutritional activators of innate immunity in EAE.

Disclosure of Interest: None declared

P0575 THE AUGMENTED EFFECT OF REBAMIPIDE ON MUCIN PRODUCTION BY INTESTINAL GOBLET CELLS

Y. Onozawa¹, O. Handa¹, Y. Suyama¹, A. Majima¹, M. Tanaka¹, Y. Hotta¹, T. Doi¹, Y. Horii¹, M. Morita¹, K. Mizushima¹, Y. Higashimura¹, O. Dohi¹, T. Okayama¹, N. Yoshida¹, K. Kamada¹, K. Katada¹, K. Uchiyama¹, T. Ishikawa¹, T. Takagi¹, H. Konishi¹, Y. Naito¹, Y. Itoh¹

¹Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan

Contact E-mail Address: onozawa@koto.kpu-m.ac.jp

Introduction: The prophylaxis and treatment for acetyl salicylic acid (ASA)-induced small intestinal injury is urgently required. Recently, we found that rebamipide (Reb), a gastro muco-protective drug, protects small intestinal mucosa from ASA-induced injury in human clinical trial using a capsule endoscopy (PLoS ONE 2015). However, the precise mechanism by which Reb protects ASA-induced small intestinal injury is not clear yet. Although MUC2, a main component mucin secreted by goblet cells, has been reported to play an essential role in the protection of epithelial cells, the effect of Reb on MUC2 production has not been investigated.

Aims & Methods

Aim: In this study, we investigated whether Reb affects on mucin secretion of goblet cells.

Materials and Methods: We used LS174T cell as a goblet cell line. The concentration of Reb (1-100μM for 24hrs) we used in this study did not affect cell viability. After Reb addition to LS174T cells, samples were taken for the following analysis at 6hr and 24hr. Subsequent mucin production was assessed by PAS staining, and MUC2 expression was assessed by PCR and WB (whole cell). Since, the mucin secretion is hard to detect by WB, we used dot-blot for the detection of secreted MUC2.

Results: Reb strongly up-regulated the positivity of PAS staining in LS174T, suggesting the increased production of intracellular mucin production. To confirm this phenomenon we assessed the MUC2 expression by PCR and WB and found that Reb significantly increased MUC2 mRNA and its protein expression in whole cell lysate of LS174T. In order to assess the subsequent secretion of mucin by LS174T, we assessed MUC2 protein expression in the supernatant of Reb conditioned LS174T using dot-blot method, and found that Reb significantly increased the secretion of MUC2 in a concentration dependent manner.

Conclusion: Taken together, the protective effect of Reb on ASA-induced mucosal injury in small intestine might depend on its ability to increase mucin secretion by small intestinal goblet cell.

Disclosure of Interest: Y. Onozawa: None declared, O. Handa: None declared, Y. Suyama: None declared, A. Majima: None declared, M. Tanaka: None declared, Y. Hotta: None declared, T. Doi: None declared, Y. Horii: None declared, M. Morita: None declared, K. Mizushima: None declared, Y. Higashimura: None declared, O. Dohi: None declared, T. Okayama: None declared, N. Yoshida: None declared, K. Kamada: None declared, K. Katada: None declared, K. Uchiyama: None declared, T. Ishikawa: None declared, T. Takagi: None declared, H. Konishi: None declared, Y. Naito: None declared, Y. Itoh Financial support for research: Otsuka Pharmaceutical Co. LTD

P0576 RISK OF AUTOIMMUNE DISEASES AND FREQUENCY OF SERUM ANA POSITIVITY IN NON-CELIAC WHEAT SENSITIVITY

A. Carroccio¹, A. D'Alcamo², M. Soresi², M. Carta², F. Adragna², F. Cavataio³, G. Friscia⁴, A. Seidita², G. Taormina², S. Iacono³, P. Mansueto²

¹Department of Internal Medicine, Giovanni Paolo II Hospital of Sciacca, Agrigento, ²Department of Internal Medicine, University Hospital of Palermo, Palermo, Italy, ³Pediatric Gastroenterology, Di Cristina Hospital, ARNAS Civico, Palermo, ⁴Clinical Pathology, Giovanni Paolo II Hospital of Sciacca, Agrigento, Italy

Contact E-mail Address: acarroccio@hotmail.com

Introduction: Non-celiac wheat sensitivity (NCWS) has raised great interest but little is known about the risks linked to this condition. We evaluated the frequency of autoimmune diseases (AIDs) and of serum anti-nuclear antibodies (ANA) in NCWS patients.

Aims & Methods: A group of NCWS patients, composed of 131 subjects (121 F, mean age 39.1 years), belonging to a historical cohort retrospectively evaluated, was studied. These patients had been recruited at two Internal Medicine Institutes. Two groups of age- and sex-matched controls, respectively composed of celiac (CD) and irritable bowel syndrome (IBS) patients, were also chosen. A pre-structured questionnaire was used to record any co-existent AIDs. ANA titers were evaluated by immuno-fluorescence.

Results: An associated AID was observed in 29% of NCWS patients (Hashimoto’s thyroiditis 29 cases, psoriasis 4 cases, type 1 diabetes 4 cases, mixed connective tissue disease 1 case, ankylosing spondylitis 1 case), in 21% of CD (not statistically significant) subjects and in 4% of IBS controls (P<.0001). Serum ANA were positive in 46% of NCWS (median titer 1:80), in 24% of CD (P<.0001) and in 2% of IBS (P<.0001) cases. An association between ANA positivity and the presence of the DQ2/DQ8 haplotypes and with the presence of duodenal lymphocytosis was found.

Conclusion: Our data showed a strong tendency towards autoimmunity in the NCWS patients, characterised by both associated AIDs and serum ANA positivity and raised the question of an overlap between NCWS and CD.

Disclosure of Interest: None declared

P0577 ROUTINE SMALL BOWEL BIOPSIES IS A COST EFFECTIVE STRATEGY IN THE INVESTIGATION OF IRON DEFICIENCY ANEMIA

E. Broide¹², S. Matalon¹, M. Leshno³, H. Shirin¹²

¹Gastroenterology, Assaf Harofeh Medical Center, Zerifin, ²Tel Aviv University, Tel Aviv, Israel, ³Buiseness of Administration, Tel Aviv University, Tel Aviv, Israel

Contact E-mail Address: efibroide@yahoo.com

Introduction: Iron deficiency anemia (IDA) is a common disorder. Half of the celiac disease (CD) patients have IDA at diagnosis. There is no consensus regarding the need for routine small bowel biopsies (SBB) in IDA patients.

Aims & Methods: To compare two strategies; strategy A- routine SBB during EGD in any patient with IDA regardless celiac serology status vs. strategy B- SBB only in IDA patients with positive serology. The main outcomes were quality adjusted life years (QALY), average cost and the incremental cost effectiveness ratio (ICER).

We used a state transition Markov model. Patients were placed into 5 health states in each cycle; No CD, undiagnosed CD, potential CD, CD under normal diet, CD under gluten-free diet, death. One way sensitivity analyses was performed on all variables and two way sensitivity analyses on selected variables were done.

Results: Performing SBB regardless the serological results yielded 19.888 QALY in strategy A compared to 19.887 if performed only in patients with positive serology. Prevalence of CD in IDA patients, utility of CD and probability of identifying CD due to symptoms were the most influential parameters. The average cost of strategy A was 218.10$ vs. 234.17$ in strategy B. As long as the cost of SBB is less than 67$, performing SBB to all patients with IDA dominates the strategy of strategy B, performing SBB only in positive serology patients. These results are independent of the costs of serological test (within a range of 60$-80$). However, when the cost of SBB is higher than 67$, the dominant strategy depends on both the cost of SBB and the cost of the serological tests. In terms of ICER, as long as the cost of biopsy stays under 77$, conducting routine SBB in all patients with IDA is still the preferred strategy. Monte Carlo simulation demonstrated that SBB to all IDA patients yielded the same QALY but with lower costs than the strategy of selected SBB.

Conclusion: Our model suggests that EGD with routine SBB appears to be a cost-effective approach with improved QALYs in patients with IDA when the prevalence of CD is 5% or greater. SBB should be a routine screening tool for CD among patients with IDA, regardless of their celiac antibody status.

Disclosure of Interest: None declared

P0578 AND WHEN IS NOT CELIAC DISEASE?: DIAGNOSIS DILEMMA IN SERONEGATIVE VILLOUS ATROPHY

E. Gravito-Soares¹, M. Gravito-Soares¹, C. Lérias¹, C. Sofia¹

¹Gastroenterology, Centro Hospitalar e Universitário Coimbra, Coimbra, Portugal

Contact E-mail Address: es18497@gmail.com

Introduction: Celiac disease is an immune-mediated pathology in individuals with genetic susceptibility to gluten that leads to variable degrees of villous atrophy. However the villous atrophy seronegative to celiac disease (SNVA) implies a diagnosis and therapy dilemma in clinical practice.

Aims & Methods: Retrospective study of all biopsies with villous atrophy, performed between 2000 and 2015. That was conducted a research of the words ‘villous/villousity atrophy' in pathology database. Of the total of 374 results, were excluded biopsies with extra-duodenal histology (126), absence of duodenal villous atrophy (97), no search/positive serology for celiac disease (79), no medical records (26) and multiple biopsies for the same patient (17). Of the remaining 29 patients with villous atrophy and negative serology for celiac disease were recorded clinical and analytical characteristics, diagnosis and therapy.

Results: Patients with SNVA had a mean age 50.1 ± 17.2years, without gender differences (15♀:14♂). Approximately 86.2% (n=25) had symptoms, mainly diarrhea, weight loss and anorexia. The malabsorption syndrome occurred in 72.4% (21/29) with microcytic anemia in 71.4% (15/21). Twelve patients had other autoimmune diseases (41.4%). Endoscopic findings consistent with celiac disease were present in 62.1% (n=18). The villous atrophy were mild-moderate in 75.9% (22/29) and severe in 24.1% (7/29). The villous atrophy associated with intraepithelial lymphocytosis occurred in 37.9% (11/29). Only 2 patients did HLA DQ2/8, both positive. The main identified etiologies were drug iatrogenic (n=6), seronegative celiac disease and common variable immunodeficiency (n=5), refractory celiac disease, duodenal Crohn's disease, Whipple's disease and unclassified sprue (n=2). Therapy was made in 26 patients, with response in 69.2% (18/26), being complete in 61.1% (11/18).

Conclusion: Duodenal villous atrophy is the final common event to several aggressor agents. Excluding celiac disease, differential diagnosis must be made with multiple pathologies, in order to establish the appropriate directed therapeutic, with clinical and histologic improvement in the most cases.

Disclosure of Interest: None declared

P0579 RISK OF COMMUNITY-ACQUIRED PNEUMONIA AMONG PATIENTS WITH COELIAC DISEASE COMPARED TO THE GENERAL POPULATION: A POPULATION BASED COHORT STUDY

F. Zingone¹², A. Abdul Sultan², C. J. Crooks², L. J. Tata², C. Ciacci¹, J. West²

¹Department of Medicine and Surgery, University of Salerno, Salerno, Italy, ²Division of Epidemiology and Public Health, University of Nottingham, Nottingham, United Kingdom

Contact E-mail Address: Fabiana.Zingone@nottingham.ac.uk

Introduction: Our aim was to quantify the risk of community-acquired infective pneumonia (CAP) among patients with coeliac disease (CD), vaccinated and unvaccinated against pneumococcus, compared to the general population.

Aims & Methods: We identified all subjects with diagnosed CD within the Clinical Practice Research Datalink linked with Hospital Episodes Statistics between 1^st April 1997 and 31^st March 2011 and up to 10 controls per CD patient by frequency matching within 10-year age bands. We calculated rates per 1000 person-years of the first CAP among all patients with CD and controls, separately in those vaccinated and unvaccinated against pneumococcus, and in CD patients before and after their diagnosis. We used a Cox regression model to estimate the hazard ratio (HR) of pneumonia among CD patients compared to the controls.

Results: Among 9,803 CD patients and 101,755 controls, respectively there were 179 (1.82%) and 1864 (1.83%) CAP events. The overall rate of CAP in CD was 3.42 per 1000 person-years and 3.12 per 1000 person-years in controls. We found an increased risk of pneumonia among the unvaccinated CD patients compared to unvaccinated controls (HR 1.28, 95% CI 1.02-1.60), but not in vaccinated CD patients compared to vaccinated controls (HR 0.88, 95% CI 0.70-1.10). The increased risk in unvaccinated CD subjects was limited to those younger than 65 years, was particularly increased around the time of diagnosis (HR 2.31, 95% CI 1.03-5.19 within 1 year after diagnosis) and was maintained for more than 5 years after diagnosis (Table).

Table. Pneumonia risk: timing from CD diagnosis (unvaccinated subjects younger than 65 years old)

Time period	N events in CD	Rate in CD per 1000	UnadjustedHR	Adjusted HRa
Before diagnosis
+1 year	21	1.43	1.45 (0.93-2.24)	1.62 (1.04-2.53)
within 1 year	13	4.62	4.66 (2.68-8.10)	4.69 (2.69-8.18)
After diagnosis
within 1 year	6	2.28	2.33 (1.04-5.21)	2.31 (1.03-5.19)
1-4 years	19	2.12	2.14 (1.35-3.39)	2.11 (1.39-3.35)
+ 5 years	31	1.59	1.60 (1.11-2.31)	1.63 (1.13-2.36)

a: adjusted for gender, calendar year; body mass index; smoking; Charlson index; socioeconomic status; Reference is controls group

Conclusion: Unvaccinated people with CD under the age of 65 have a higher risk of CAP compared to the general population around the time of diagnosis and subsequently. Pneumococcal vaccination in people with CD following diagnosis and treatment would appear to be good medical advice.

Disclosure of Interest: None declared

P0580 REVISITING DIAGNOSTIC FEATURES OF REFRACTORY CELIAC DISEASE OF TYPE I

G. Malamut¹, P. Rompteaux¹, B. Meresse², S. Khater¹, N. Brousse³, V. Verkarre³, C. Derrieux³, E. Macintyre³, N. Cerf-Bensussan², C. Cellier¹

¹Hôpital Européen Georges Pompidou, ²UMR1163 Institut Imagine, ³Hôpital Necker Enfants Malades, Paris, France

Contact E-mail Address: georgia.malamut@egp.aphp.fr

Introduction: A small group of celiac patients becomes refractory to a gluten-free diet (GFD). In contrast with refractory celiac disease of type II (RCDII), characterized by clonal expansion of intraepithelial lymphocytes with abnormal phenotype, RCDI can be scarcely distinguished from active celiac disease at diagnosis.

Aims & Methods

Aim: We aimed to assess RCDI for its clinical, biological, histopathological features and precise phenotype of intestinal lymphocytes at diagnosis.

Patients and Methods: 202 patients, with intestinal villous atrophy refractory to a GFD, were investigated in European Georges Pompidou Hospital between 2000 and 2013. Clinical and histopathological study allowed diagnosis of RCDI in 20 patients.

Results: In our institution, diagnosis of RCDI is performed in 10% of patients with intestinal villous atrophy refractory to a GFD. Main patients (17/20) with RCD I (15F/5M; mean age at diagnosis of celiac disease (CD): 41 years) were primary refractory to a GFD. Three patients were secondary refractory to a GFD within 25 years [14-35 years] after diagnosis of CD. At diagnosis of RCDI, persistent positive serology was found in 8 patients. One third of RCDI patients had severe malnutrition with low albuminemia and iron deficiency. Except one patient HLA-DQ8, all others were HLA-DQ2 and six patients (30%) were HLA-DQ2/DQ2. Seven patients (35%) had extra-intestinal autoimmune diseases, mainly autoimmune thyroiditis, 44% (7/16) of patients had serum auto-antibodies mainly, anti-nuclear antibodies. At diagnosis, half RCDI patients (10/20) had severe intestinal villous atrophy with increased count of IEL (CD3 + CD8+: 69 %) and thickened collagenous subepithelial layer was found in duodenal mucosa of 25% of them (5/20). Increased frequency of CD3 + CD4+ IEL (10.5%) was found in comparison with active celiac patients (4.5%; p=0.01) or CD patients under GFD (p < 0.05). Microscopic colitis, of collagenous or lymphocytic type, was observed in 86% (6/7) of patients investigated with colonoscopy.

Conclusion: Increased intestinal CD4+ IEL count, collagenous sprue (25%) and microscopic colitis (86%) are histopathological and phenotypic features of diagnosis of RCDI. High frequency of HLA-DQ2 homozygosity (30%) and associated extra-intestinal autoimmune diseases (35%) suggest an autoimmune mechanism.

Disclosure of Interest: None declared

P0581 SMALL INTESTINE DIGITAL HISTOMORPHOMETRY FOR CELIAC DISEASE

J. Taavela¹, A. Popp¹², R. P. Anderson³, J. Isola⁴, M. Mäki¹

¹Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland, ²University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania, ³ImmusanT, Inc., One Kendall Square, Building 200, LL, Suite 4, Cambridge, MA 02139, United States, ⁴Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland

Contact E-mail Address: juha.taavela@uta.fi

Introduction: Digital image analysis of small intestinal biopsies, allowing quantitative villus height crypt depth ratios measurements (VH:CrD) and CD3-positive cell counts, holds promise in celiac disease research. We validated our morphometric procedures using virtual microscopy of small intestinal biopsy sections and compared the results to those of conventional microscopy.

Aims & Methods: Standard H&E stained biopsy specimens (n=144) from adult celiac disease patients and non-celiac disease controls were scanned and analyzed using a dedicated virtual microscopy platform - Celiac Slide Viewer. The specimens, which comprised different grades of mucosal injury, were evaluated morphometrically on computer screen by two accredited evaluators. Specimens with tangential cutting were included. The intra- and interobserver variations for VH:CrD and CD3+ densities (IELs/100 epithelial cells) were analyzed with the Bland-Altman method and intraclass correlation.

Results: Both observers measured 93 samples out of 144 (65 %) for VH and CrD readings. The rejected samples were evaluable neither for morphometry measurements or Marsh-Oberhuber classes because of tangential biopsy cuttings. CD3+ stained specimens were available from 107 patients. The intraobserver analysis of VH:CrD showed a mean difference of -0.019 with limits of agreement from −0.394 to 0.432; the standard deviation (SD) was 0.211. The mean difference in interobserver analysis was 0.0047, limits of agreement −0.544 to 0.554, and SD 0.280. The intraclass correlation coefficient in intraobserver variation was 0.985 and that in interobserver variation 0.970. CD3⁺ IEL density showed a SD of 18.5% and an intraclass correlation coefficients of 0.957.

Conclusion: The results indicate that digital morphometry is a powerful tool for measuring even small injury changes of small intestinal mucosa. Virtual microscopy allows image sharing via internet, saving and tracking of measurements. A conversion table between Marsh-Oberhuber grouped classification and quantitative morphometry is shown.

Disclosure of Interest: None declared

P0582 FLOW CYTOMETRY OF INTRAEPITHELIAL LYMPHOCYTES INCREASES CELIAC DISEASE DIAGNOSTIC SENSITIVITY

J. Valle¹, J. M. T. Morgado², J. Ruiz-Martín³, A. Guardiola¹, M. Lopes-Nogueras¹, A. García-Vela¹, B. Martín-Sacristán⁴, L. Sánchez-Muñoz²

¹Gastroenterology, ²Instituto de Estudios de Mastocitosis de Castilla La Mancha, ³Pathology, ⁴Pediatrics, Complejo Hospitalario de Toledo, Toledo, Spain

Contact E-mail Address: julio.valle@telefonica.net

Introduction: Celiac disease diagnosis can be difficult in patients with minimal histologic changes (Marsh 0-1) or when there is disagreement between serology and histology. Celiac disease is characterized by an increase in the total number of intraepithelial lymphocytes (IELs) in the small bowel mucosa, with an increase in the subset of γ/δ T-cell receptor-bearing IELs along with a decrease in the subset of CD3-CD103+ IELs (celiac immunophenotype).

Aims & Methods: Our aim was to assess the role of the analysis of IELs by flow cytometry in the diagnosis of celiac disease, both in adults and children.

Material and Methods: 317 patients with suspicion of celiac disease (194 adults and 123 children) were included in the study. In all patients serum IgA tissue transglutaminase antibody levels were determined and six biopsy samples from the second part of duodenum were obtained during an upper gastrointestinal endoscopy. Four biopsies were fixed in 10% formalin for histologic assessment and two biopsies were placed in cold 0.9% saline solution for flow cytometric analysis of IELs. Celiac disease diagnosis was based in a positive serology and compatible changes in duodenal biopsy (Marsh 2-3). In doubtful cases, diagnosis of celiac disease was supported by a positive clinical and serological response to a gluten-free diet.

Results: 68 adults (45 female; median age: 35 years; range: 14-74 years) and 96 children (54 female; median age: 7 years; range: 0–13 years) were diagnosed of celiac disease. Histology had a 89% sensitivity and a 97% specificity for the diagnosis of celiac disease. The presence of a compatible celiac immunophenotype in the flow cytometric assessment of IELs had a 93% sensitivity and a 96% specificity. Considering the presence of either Marsh 2-3 in duodenal biopsies and/or a compatible immunophenotype as diagnostic of celiac disease, we obtained a sensitivity of 99% and a specificity of 97% (Table 1). Flow cytometry allowed us to diagnose celiac disease in 10 adults and 6 pediatric patients with mild histologic changes (Marsh 0-1).

Table 1.

Diagnostic accuracy of the combination of histology and flow cytometry of IELs in suspected celiac disease.

Marsh 2-3 and/or celiac immunophenotype	Celiac disease	No celiac disease
Positive (%)	162 (98.8%)	4 (2.6%)
Negative (%)	2 (1.2%)	149 (97.4%)
Sensitivity (95%CI)	99% (96-100%)
Specificity (95%CI)	97% (93-99%)
PPV (95%CI)	96% (94-99%)
NPV (95%CI)	97% (95-100%)

CI: confidence interval. PPV: Positive predictive value. NPV: Negative predictive value.

Conclusion: In patients with suspicion of celiac disease the combined use of histology and flow cytometry of IELs increases diagnostic sensitivity without decreasing specificity.

Disclosure of Interest: None declared

MONDAY, OCTOBER 26, 2015   09:00-17:00

NUTRITION I – HALL 7__________

P0583 THE CORRELATION BETWEEN INCREASED LEPTIN CONCENTRATIONS AND PECULIARITIES OF GASTRIC MUCOSA IN PATIENTS WITH PROLONGED USE OF NSAIDS

A. Antonenko¹, T. Beregova², A. Svintsitskyi¹

¹Department of Internal Medicine №3, Bogomolets National Medical University, ²Department of Pharmaco-Physiology, Taras Shevchenko National University of Kyiv, Kiev, Ukraine

Contact E-mail Address: tonyaant@yandex.ua

Introduction: Leptin is a hormone produced primarily by adipocytes and plays important role in nutritional status and in obesity. Recently, the presence of leptin as well as the expression of its receptors was detected in rat and human stomach. It is known that the level of leptin in males with DU is increased. Data about the correlation between the leptin levels with severity of gastritis, H. pylori (Hp) and sex are controversial (Roper J.L. et al. 2008; Khudlur S. et al. 2011).

Aims & Methods: The aim of our study was to determine a correlation between leptin levels with sex, Hp status, BMI and histological features of gastric mucosa (GM) in patients with prolonged use of non-selective NSAIDs. We examined 94 patients who regularly during the last month used non-selective NSAIDs. Excluded from this study were those who had used proton pump inhibitors or antibiotics in the previous month, patients with prior history of gastroduodenal surgery and pregnant or lacting women. The mean-age of these patients was 63.2 ± 6.0. For all of these individuals gastroscopy with further morphological examination, laboratory examinations were performed. All patients were divided in two groups: with erosive gastropathy and without visible changes of GM. The serum leptin levels were determined in all patients using sandwich leptin solid phase ELISA (DRG-instrument GmbH-Germany). Endoscopically obtained biopsies were stained with hematoxylline and eosine. Severity of inflammation was graded according to modified Sydney classification. The presence of Hp was determined by rapid urease test/CLO test. Normal distribution of studied parameters for each sampling was checked using Shapiro-Wilka’s criteria. Average value (M) error and standard deviation (SD) were calculated to discover significant changes of investigated indices. Sampling comparison was performed using the paired t-test and ANOVA. Differences among values were considered statistically significant if p < 0.05. Correlations were analyzed using the Pearson test.

Results: NSAIDs-gastropathy was detected in 63 patients, in 31 patients visible changes of GM were absent. As expected, leptin correlated significantly with BMI (r²=0.43) and it was higher in women (15.59 ± 6.69) vs men (11.05 ± 6.6), p=0.023. Serum leptin level was increased on 25 % in patients with erosive changes of GM (p=0.04). Of the 63 subjects 17 were Hp+ and 46 were Hp-. Of 31 subjects 18 were Hp+ and 13 were Hp-. The groups were not significantly different in terms of gender, height, weight or BMI. Serum leptin levels were significantly lower in Hp+ (9.78 ± 4.83) vs Hp- (16.57 ± 6.19) patients with NSAID gastropathy (p=0.004). The changes between Hp+ vs Hp- patients without visible changes of GM were not statistically valid (p=0.891). Correlation between the level of leptin and the severity of gastritis was not observed in our study (p=0.86).

Conclusion: Serum leptin correlates with BMI, sex and presence of erosions. Hp colonization is associated with reduced serum leptin levels, independent of BMI. An increase in serum leptin in patients with NSAIDs-gastropathy may be a defense mechanism that can be used as prognostic factor for the prediction of the erosive NSAIDs-gastropathy in patients with prolonged use of NSAIDs.

Disclosure of Interest: None declared

P0584 SOCIAL PHOBIA AND QUALITY OF LIFE IN MORBIDLY OBESE PATIENTS BEFORE AND AFTER BARIATRIC SURGERY

A. Mirijello¹, C. D'Angelo², G. Vassallo³, C. Tarli³, M. Antonelli³, F. Bernardini³, L. Sestito³, A. Ferrulli⁴, A. Gasbarrini³, G. Addolorato³

¹IRCSS Casa Sollievo della Sofferenza, ²Padre Pio Rehabilitation Centres Foundation ONLUS, San Giovanni Rotondo, ³Institute of Internal Medicine, Catholic University of Rome, Rome, ⁴IRCCS Policlinico San Donato, San Donato Milanese, Italy

Contact E-mail Address: g.addolorato@rm.unicatt.it

Introduction: Morbidly obesity is characterized by physical and psychological comorbidities which are associated with reduced quality of life. Bariatric surgery has been linked to a reduction of psychopathology other than to a reduction of weight and improvement in physical functioning

Aims & Methods: Aim of the present study was to compare psychological features of morbidly obese patients, before and after bariatric surgery, assessing social phobia and quality of life. A total of 46 morbidly obese patients were enrolled in the study. 20 patients were waiting for bilio-pancreatic diversion (group A), while 26 patients had already undergone surgical procedure (group B). Social phobia, fear for the body-shape and quality of life were assesed using appropriate psychometric tests.

Results: The percentage of patients showing social phobia was significantly higher compared to a sample of healthy controls (p=0.004), both in group A (p=0.003) and in group B (p=0.029). No differences in percentage of patients affected by social phobia were found between two groups. A significantly higher percentage of patients affected by distress about the body (p < 0.0001) was found in group A with respect to group B. A reduction of quality of life was found in both groups.

Conclusion: The present study shows a high prevalence of social phobia in a population of morbidly obese patients, both before and after surgery. A general reduction of quality of life was also observed, with a partial improvement after surgery. Future studies are needed to clarify the relationship between social phobia and quality of life in surgically-treated morbidly obese patients.

Disclosure of Interest: None declared

P0585 INCREASED EXPRESSION OF PPARΓ IN CD24 KNOCKOUT (KO) MICE AND GENDER-SPECIFIC METABOLIC CHANGES: A UNIQUE MODEL OF INSULIN-SENSITIVE OBESITY

S. Shapira¹, D. Kazanov¹, N. Maharshak¹, R. Dankner², I. Zvibel³, F. Bedny⁴, S. Kraus⁵, A. Nadir⁵

¹Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, ²Epidemiology and Preventive Medicine, The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, ³The Research Center for Digestive Tract and Liver Diseases, Tel-Aviv Sourasky Medical Center, and The Sackler Faculty of Medicine, Tel-Aviv University, ⁴Pathology Institute, ⁵Integrated Cancer Prevention Center, Sourasky Medical Center, Tel Aviv, Israel

Contact E-mail Address: nadira@tlvmc.gov.il

Introduction: Background: The heat stable (HSA)/CD24 gene encodes a heavily-glycosylated cell surface protein. CD24 expression is high in immature precursor cells and low/absent in terminally differentiated cells. It plays an important role in the adaptive immune response and homeostasis in autoimmune diseases. CD24 is highly expressed in a large variety of human cancers. The association between cancer, diabetes, and obesity is not clear. Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and regulator of adipogenesis that plays a role in insulin sensitivity, lipid metabolism, and adipokine expression in adipocytes.

Aims & Methods

Aim: To assess gender-dependent changes in CD24/HSA KO mice fed with normal and high-fat diet (HFD).

Methods: Body weight (BW), water and food consumption were closely monitored from birth in HSA^+/+ and HSA^-/- mice for one year. The trial was repeated twice). Insulin (0.5IU/kg) sensitivity and glucose (1gr/kg) tolerance was determine thrice. Adipose tissue from kidney (KF), testicular (TF), and liver (LF) were isolated from KO and WT mice. High-throughput sequencing of stool 16S rRNA genes was assessed in the enteric microbial populations of the KO and WT mice, male and female, normal and HFD consumers. N=10 in each group. Taxa analysis was performed on the core taxa prevalent in more than >25% of samples. Extraction of vascular fraction from adipose tissues was performed and primary cultures of adipocytes were established.

Results: Water and food consumption was similar for the KO and WT mice in normal and HFD. Mean BW of the KO was higher than that of their WT littermates, particularly in males and surprisingly with greater insulin sensitivity (10-20%) and glucose uptake (30%). It remained valid for mice fed with HFD. No such differences were observed among females. Significant differences in BW, KF, TF and LF were demonstrated between CD24 KO and WT mice. Aadipocytes size of the KO (8258 ± 2359 uM²) was significantly higher than that of the WT (5471 ± 2030 uM²) mice (P <3.51E-09). PPARγ expression was higher (x1.5) in CD24 KO mice. Enteric bacterial populations were significantly different between KO and WT mice (normal diet) by unweighted (R=0.32, P<0.01) β-diversity analysis. These differences became much more apparent when mice were kept on HFD by weighted (R=0.43, P < 0.01) and un-weighed β-diversity analysis (R=0.31, P<0.01) as well as by specific bacterial taxa.

Conclusion: 1. CD24 negatively regulate PPARγ expression in male mice. 2. The association between CD24 and insulin sensitivity, and the oncogenic potential of CD24, suggest a possible mechanism for diabetes as a cancer risk factor. 3. CD24 KO male mice may serve as a model of male early obesity and insulin sensitivity.

Disclosure of Interest: None declared

P0586 ENDOSCOPIC REVISION WITH ARGON PLASMA COAGULATION FOR FAILED ROUX-AND-Y GASTRIC BYPASS (RYGB). FIRST LARGE SERIES

B. Q. Sander¹, M. Galvão Neto², G. A. P. Baretta³, J. A. Schemberk Jr⁴, E. N. Usuy Jr⁵, R. J. Fittipaldi-Fernandez⁶

¹Endoscopy, Clínica Sander, Belo Horizonte, ²Endoscopy, Gastro Obeso Center, São Paulo, ³Endoscopy, EndoBatel Endoscopy Service, ⁴Endoscopy, Clínica Obeso Gastro, Curitiba, ⁵Endoscopy, Usuy Clínica Médica, Florianópolis, ⁶Endoscopy, Endogastro Med Service, Rio de Janeiro, Brazil

Contact E-mail Address: brunosander@hotmail.com

Introduction: The weight regained has been a described growing problem in patients after bariatric surgery, especially at long term. This weight regained is multifactorial and often associated with dilation of Gastrojejunostomy (GJ), allowing a faster gastric emptying and therefore greater food intake. For the patients with significant weight regain after failed conservative approach, some revisional procedures are attempted and more recently endoscopic revisional procedures have been described.

Aims & Methods: To evaluate the safety and effectiveness of argon plasma coagulation (APC) decreasing the diameter of the gastro-enteric anastomosis in patients who have undergone Roux-and-Y Gastric Bypass (RYGB) for morbid obesity and regained weight associated to dilation of the GJ.

From jan-2014 to jan-2015 215 RYGB subjects with weight regain, a dilated anastomosis (more than 18mm in diameter) and at least 2 years from procedure were submitted APC application at GJ had their data reviewed from a prospective designed databank. Interval between an APC session applications was 60 days, with a maximum of 03 applications. APC set was at 2-3L/m with 65-75W. GJ diameter target was to reduced it up to 8-12mm estimated with pre-measured open grasper. At first APC session pre-op weight and BMI, post-op weight nadir, actual weight and BMI and estimated diameter of GJ were the variables collected. At each following session weight, BMI and estimated GJ diameter were taken. Complications during treatment were also collected. Data were analyzed with descriptive statistics, student's t test and Spearman correlation.

Results: Of the 215 patients, 82.8% were women and 17.2% were men. Average time between bariatric surgery and the first APC was 97.42 months (±41.64. Range: 25–175) and average weight regained in this interval was 20.25kg (±9,95. Range: 3-63). The mean diameter of the anastomosis was 24.81mm (±5,34. Range: 16-40) and the average number of APC sessions were 1.36 times (±0.52. Range: 1-3). The average reduction of anastomotic diameter was 13.52mm (±6,19. Range: 4-34) and the final average diameter was 11,3mm (±3,32. Range: 5-28). The average weight loss between the first and last APC was 13,77kg (±6,99. Range: -4,55-35,62) and the average decrease of BMI was 4,66kg/m² (±2,55. Range: -1,69-11,07). 69 patients (32,1%) did not achieve the target GJ diameter and 01 patient (0.5%) did not lose weight even with the desired GJ diameter. From the 27 subjects followed up to 6 months no regain weight was noted. Of the 215 patients APC, 35 (16.27%) required dilatation balloon due to symptomatic stenosis at least once. No further complications were reported.

Conclusion: Argon Plasma Coagulation (APC) has been shown to be an effective and safe endoscopic technique for the reduction of gastro enteric anastomosis in patients undergoing bariatric surgery who have regained weight with dilation of the anastomosis.

Disclosure of Interest: None declared

P0587 INTRAGASTRIC BALLOON TO TREAT EXCESS WEIGHT: A LARGE BRAZILIAN EXPERIENCE

R. J. Fittipaldi-Fernandez¹, B. Sander², C. F. Diestel³⁴, A. F. Teixeira⁵, E. Usuy⁶

¹Digestive Endoscopy, Endogastro Med Service, Rio de Janeiro, ²Digestive Endoscopy, Sander Clinic, Belo Horizonte, ³Nutrition Division, Endogastro Med Service, ⁴Nutrition Department, University of Rio de Janeiro State, Rio de Janeiro, ⁵Digestive Endoscopy, Gastros Bahia, Feira de Santana, ⁶Digestive Endoscopy, Usuy Clinic, Florianópolis, Brazil

Contact E-mail Address: ricfittipaldi@hotmail.com

Introduction: Endoscopic methods, especially the intragastric balloon (IGB), have been shown to be effective for the treatment of excess weight.

Aims & Methods

Objective: To assess the efficacy and complications of excess weight treatment with an IGB in patients seen at the Endogastro Med Service clinic and Sander clinic.

Methods: A total of 2727 patients were analyzed. A liquid-filled IGB with a volume of 600 to 700 ml was used. The patients had a minimum initial body mass index (BMI) of 27 kg/m2 and were followed up by a multidisciplinary team consisting of a nutritionist, a doctor and a psychologist. For statistical analysis, the patients were divided into groups according to sex and degree of excess weight (overweight and grade I, II and III obesity). Data were analyzed using descriptive statistical methods, the Student t-test, and analysis of variance followed by the Tukey post-test. The level of significance was set at p < 0.05.

Results: 188 patients were excluded from the analysis: 114 (4.18%) due to early IGB removal, 27 (0.99%) due to absence of weight loss or weight gain, 9 (0.33%) due to incomplete data. The incidence of contamination of the balloon liquid filling was 0.22% (n=6) and the incidence of leakage was 0.55% (n=15); pregnancy was 0.33% (n=9); Wernick Korsakoff syndrome due to excessive vomiting was 0.03% (n=1), pancreatitis, early removal due to intake non steroidal anti inflammatory drugs necessity, gastric perforation and upper digestive bleeding was 0.03% each (n=1). 0.11% (n=3) removed balloons were from other teams’ patients. Of the 2539 remaining patients, 1908 were women and 631 were men. Mean age was 37.56 years. The patients showed a significant weight loss, with a significantly lower final BMI (mean: 28.91 ± 7,83 kg/m2; range: 18.98-58) than the initial BMI (mean: 36.23 ± 5.70 kg/m2; range: 27-74.74) (p < 0.0001). Mean BMI reduction was 7.38 ± 3.99 kg/m2 (range: 0.25-29.79). Mean percent weight loss was 20.09 ± 7.61% and mean percent excess weight loss (EWL) was 74.23 ± 36.71% (range 3.99-336.14). The treatment success rate (%EWL > 25) was 94,7%. Percent EWL was higher in the overweight group (147%EWL), followed by obesities grades I (82.91%), II (62.12%) and III (51.44%) sequentially (p < 0.0001). Percent EWL was also higher in women (76.31%EWL) than in men (68.08%EWL) (p < 0.0001).

Conclusion: Endoscopic treatment of excess weight with an IGB has been established as an excellent therapeutic option for patients of both genders with overweight or different degrees of obesity.

Disclosure of Interest: None declared

P0588  A NEW APPROACH IN THE TREATMENT OF WEIGHT REGAIN AFTER BARIATRIC SURGERY: THE ARGON PLASMA COAGULATION OF THE ANASTOMOSIS

R. J. Fittipaldi-Fernandez¹, C. F. Diestel², B. Sander³, A. F. Teixeira⁴, E. Usuy⁵

¹Digestive Endoscopy, Endogastro Med Service, ²Nutrition Division, Rio de Janeiro State University, Rio de Janeiro, ³Digestive Endoscopy, Sander Clinic, Belo Horizonte, ⁴Digestive Endoscopy, Gastros Bahia, Feira de Santana, ⁵Digestive Endoscopy, Usuy Clinic, Florianópolis, Brazil

Contact E-mail Address: ricfittipaldi@hotmail.com

Introduction: The weight regain is a problem after bariatric surgery, it is multifactorial, and occurs, in part, by dilatation of the gastro-jejunal anastomosis, which causes a faster gastric emptying and increased food intake.

Aims & Methods

Objective: To evaluate the efficacy of endoscopic argon plasma coagulation (APC) of the anastomosis and of the gastric pouch aiming to reduce the diameter thereof.

Methods: We analyzed 40 patients. 35 of them underwent at least 03 sessions of APC. Two patients underwent only one session and three patients underwent only two sessions, due to an immediate reduction of the anastomosis to a diameter smaller than 12 mm after the first or the second session, which is the procedure target. The APC was held at the anastomosis and in gastric pouch. 80w power was used in the 1st session, and 70w power APC in the following, with an Argon flow of 2L/min. The time interval between sessions was eight weeks. The objective is to obtain an anastomosis with a diameter between 8-12 mm. The patient’s weight had been evaluated in each APC session and six months after the latest APC session. Data were analyzed with descriptive statistics, student's t test and Spearman correlation.

Results: Of the 40 patients, 87.5 % were women (n=35). The mean regained weight in relation to the maximum weight lost (Nadir) after bariatric surgery was 46.60 % (16.45-123.68). There was a significant reduction in body mass index (BMI) at the end of the analysis (30.78 ± 4.81 kg/m2) compared to the initial mean BMI (mean BMI= 36.34 ± 4.78 kg/m2) (p <0.0001). The average loss of the regained weight was 71.44% (12.09-169.57). The average weight loss in Kg was 15.47 (4-40.5). The average diameter of the anastomosis in the beginning of the treatment was 36,18 mm (25-50mm) and at the end of the treatment 11.02 (6-12mm).

Conclusion: The APC has demonstrated great efficacy in the treatment of weight regain after bariatric surgery of gastric bypass in Roux-Y.

Disclosure of Interest: None declared

P0589 ADIPOKINES, INFLAMMATORY AND INSULIN RESISTANCE PARAMETERS: CAN THEY BE GOOD MARKERS OF METABOLIC SYNDROME AFTER LIVER TRANSPLANTATION?

E. G. Vilela¹, L. R. Anastácio², K. G. D. Diniz³, M. I. T. D. Correia⁴, A. S. Lima⁵

¹Internal Medicine, Federal University of Minas Gerais, Belo Horizonte, ²Nutrition, Federal University of Triangulo Mineiro, Uberaba, ³Instituto Alfa de Gastroenterologia, ⁴Surgery, Federal University of Minas Gerais, ⁵Surgery, Federal Uiversity of Minas Gerais, Belo Horizonte, Brazil

Contact E-mail Address: evilela@medicina.ufmg.br

Introduction: Metabolic syndrome (MS) and obesity are widely prevalent among liver transplant (LTx) recipients. Although there is lot of data on the role of adipokines in these diseases, studies after LTx are scarce.

Aims & Methods

Aim: To investigate the concentrations of adipokines, inflammatory and insulin resistance markers among liver recipients according to MS and its components.

Methods: This was a cross-sectional study in which serum samples from 34 patients (55.9% male; average age 54.9 ± 13.9 years; average time of 7.7 ± 2.9 years after LTx) were evaluated for analysis of adiponectin, resistin, tumor necrosis factor-alpha (TNF-a), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), C-protein reactive (CPR), HOMA-IR and free fatty acids (FFA) in 2012/2013. The dosages were uni and multivariate analyzed considering metabolic syndrome (using the Harmonizing the MS criteria) and its components.

Results: Half of the patients evaluated had MS (n=17). Higher concentration of adiponectin was observed among liver recipients that had MS (6.7 ± 4.5 mg/mL versus 3.2 ± 1.2 mg/mL; p < 0.01). Low HDL and high waist: hip ratio were considered independent predictors of adiponectin concentrations. Lower amounts of resistin were observed in those patients with high blood pressure (4.5 ± 1.6 ng/mL versus 6.2 ± 2.3 ng/mL; p < 0.01) and higher, in those with abdominal obesity (5.5 ± 4.2 ng/mL versus 4.3 ± 1.6 ng/mL). Increased FFA (0.8 ± 0.3 mEq/L versus 0.5 ± 0.3 mEq/L, p < 0.05) and HOMA-IR (4.9 ± 3.8 versus 1.6 ± 0.8) were observed in patients with MS. Independent risk factors were not identified for TNF-a, MCP-1, IL-6 and FFA.

Abstract number: P0589 Table 1.

Average and standard deviation or median, minimum and maximum of adipokines, inflammatory and insulin resistance markers of patients who underwent liver transplantation according to metabolic syndrome

Characteristic	Adiponectin (mg/mL)	Resistin (ng/mL)	TNF-a(pg/mL)	MCP-1(pg/mL)	IL-6(pg/mL)	HOMA IR	FFA (mEq/L)
Metabolic syndrome
Yes	6.7 ± 4.5**	5.0 ± 1.1	40.5 (16.6-170.2)	342.6 ± 251.8	10.4 (4.6-244.3)	4.9 ± 3.8**	0.8 ± 0.3*
No	3.2 ± 1.2	5.3 ± 2.3	40.0 (16.7-495.9)	260.9 ± 208.5	18.2 (2.0-305.2)	1.6 ± 0.8	0.5 ± 0.3

*p < 0.05; **p < 0.01.

Conclusion: MS and its components are related to increased FFA concentration and HOMA-IR. Adiponectin, resistin and inflammatory markers, such as TNF, IL-6, MCP-1 and CRP, were not good markers of metabolic syndrome in this sample of patients who underwent liver transplantation.

Disclosure of Interest: None declared

P0590 THE IMPACT OF VEGETARIAN AND VEGAN DIET ON THE INCIDENCE OF GASTROINTESTINAL SYMPTOMS

A. Budzynska¹, E. Nowakowska-Dulawa¹, M. Hartleb¹

¹Dept. of Gastroenterology&Hepatology, Medical University of Silesia, Katowice, Poland

Contact E-mail Address: budzynskaagnieszka@poczta.onet.pl

Introduction: More than a million of Polish citizens and about 420 millions of people worldwide use vegetarian diet.

Aims & Methods: To assess the impact of a vegetarian and vegan diet on the incidence of gastrointestinal symptoms.

Material: The study involved 1209 persons (73% from Poland and 27% from US), 702 (58%) used vegetarian diet, 365 (30%) vegan diet and 142 (12%) non-restrictive diet.

Methods: All participants replied to online questionnaire comprising 31 questions.

Results: People using exclusive diets were older than those without dietary restrictions (28.3 vs. 23.8 yrs, p < 0.001). American responders had higher BMI than Polish subjects (25.6 vs. 22.0 kg/m², p < 0.001), but vegetarian diet had reducing effect on body weight only in Polish population (p < 0.001). Participants from USA remained on vegetarian diet longer (81.5 vs. 63.4 months, p=0.001) and their monthly diet-related supplementary expenses were higher (199.8 vs. 111.0 €, p < 0.001) than in Polish population. 57% of vegetarians and 66% of vegans introduced their diets for healthy motives. Vegetarians and vegans reported improvement (74% and 84%), deterioration (4% and 3%) or no change (22% and 13%) in prevalence of gastrointestinal symptoms (p=0.002). In the respective groups the incidence of bloating and/or abdomen fullness decreased from 52% to 13% and from 60% to 12%, of heartburn, nausea and vomiting from 25 to 2% and from 32% to 4%, of constipation from 35% to 8% and from 44% to 4%, and taste alterations or anorexia from 11% in both groups to 2% and 3%, respectively. By contrast, after introduction of vegetarian or vegan diet the incidence of skin lesions increased from 2% to 16% and from 3% to 10%.

Conclusion: More than half of responders introduced vegetarian/vegan diet for healthy reasons and in the majority these diets reduced severity of gastrointestinal symptoms.

Disclosure of Interest: None declared

P0591 MOTIONS IN ICU: A PROSPECTIVE STUDY ON THE PREVALENCE OF DIARRHOEA IN A TERTIARY ICU

A. Elzubeir¹

¹University Hospital Birmingham, Birmingham, United Kingdom

Contact E-mail Address: amera.elzubeir@doctors.net.uk

Introduction: Diarrhoea is a frequently reported problem in Intensive Care Units (ICU). Little is known about diarrhoea prevalence and the role of different risk factors in ICU at Queen Elizabeth Hospital Birmingham (UHB) – a large tertiary centre with one of the largest single-floor ICUs in Europe.

Aims & Methods: To identify prevalence of diarrhoea in intensive care patients with a length of stay (LOS) greater than 24 hours receiving any type of enteral nutrition, in addition to determining its clinical impact i.e. on length of stay in ICU, timing of diarrhoea onset, and risk factors for diarrhoea focusing on its association with hypoalbuminemia.

A prosective study of 109 patients consecutively admitted into a mixed medical-surgical ITU during a 2-month period (October 2014- December 2014) were included into the study according to the following criteria:

1. Length of stay >24 hours

2. No diagnosis or evidence of diarrhoea on admission

3. Absence of parenteral nutrition

4. No recent admission to ICU at UHB.

Diarrhoea was defined as 3 or more liquid stools per day, or that which warranted Clostridium Difficile Toxin to be sent for microbiological analysis (such patients were presumed to have had diarrhoea).

Results: A total of 109 patients were analysed. Diarrhoea was observed in 35 patients (32%). The median day of diarrhoea onset was on the ninth day, and 66% of those had diarrhoea for four days or more. The incidence of C. Difficile infection was 3%, this occurred in a patient who was previously known to have had C. Difficile infection on a previous admission. Those with diarrhoea had double the length of stay in ICU than there non-diarrhoea counterparts (44.7 vs 22.6 days), with just under a third (31%) of their stay ICU stay being with ongoing diarrhoea. Of those with diarrhoea 29% died on ICU compared to 16% of its non-diarrhoea counterparts.

If all those with acute or chronic liver disease were excluded- 100% of patients with an albumin level of less than or equal to 26 g/L had diarrhoea. Furthermore it was noted that diarrhoea occurred in all patients with an albumin level less than 30 g/L except for those with known acute or chronic liver disease, in fact one patient with chronic liver disease awaiting liver transplant had an albumin level as low as 14 without evidence of diarrhoea.

Conclusion:

Diarrhoea was common in our ICU, its prevalence (32%) being consistent with established literature. It was associated with significantly increased ICU LOS and mortality, although any single direction of causality still remains to be established. A low stool investigation yield and low prevalence of C. difficile suggests that other non-infective causes of diarrhoea need excluding. The results from this study conclude that there may indeed be a causal link between hypoalbuminemia and prevalence of diarrhoea in ICU, with hypoalbuminemia-related diarrhoea being significantly higher in patients with an albumin level of less than or equal to 26 g/L. It remains unexplained why those with acute or chronic liver disease are not as susceptible to diarrhoea despite low albumin levels. Further research is required to establish the prevalence and pathogenesis of diarrhoea on UK ICUs, in order to develop evidence-based management plans for reducing its incidence, and its clinical and financial impact.

Disclosure of Interest: None declared

P0592 SIGNIFICANT GASTROINTESTINAL PATHOLOGY AND THE INCIDENCE OF SUBSEQUENT ANEMIA IN YOUNG MALES PRESENTING WITH IRON DEFICIENCY WITHOUT ANEMIA

D. Carter¹, E. Bardan¹, B. Avidan¹

¹Gastroenterology, Chaim Sheba Medical Center, Ramat Gan, Israel

Contact E-mail Address: dr.dancarter@gmail.com

Introduction: The etiology of iron deficiency (ID) without anemia in young males is unclear, and there are no evidence-based recommendations for the required gastrointestinal (GI) evaluation

Aims & Methods: To examine the incidence of significant GI pathology and the development of anemia during the follow-up of young males presenting with ID, but without anemia.

All young males (18-30 years) who served in the Israel Defense Forces during the years 2005-2013 and had at least a single laboratory test indicative of ID without anemia were followed until the diagnosis of significant GI pathology or discharge from military service.

Results: The study population included 2061 young males (mean age 20.7± 1.8 years). During follow-up of 3150 person years, significant GI pathologies were diagnosed in 39 patients: inflammatory bowel disease in 25 (1.2%), celiac disease in 8 (0.4%) and peptic disease in 4 (0.1%). No cases of gastrointestinal related cancer were diagnosed. Iron deficiency anemia developed during follow-up in 203 (9.8%). Lower baseline hemoglobin levels, lower ferritin levels and younger age at diagnosis were more common among those who developed anemia. The development of anemia was a predisposing factor for diagnosis of GI pathology (RR= 3.60, 95%CI 1.34-8.32, p=0.012)

Conclusion: Significant GI pathology is very uncommon in young males presenting with ID. Overt anemia developed in close to 10% of the study cohort. Therefore, we advise simple GI evaluation (celiac serology, CRP and urease breath test) as well as follow-up in this population.

Disclosure of Interest: None declared

P0593 PREBIOTIC EFFECT OF FODMAPS IN PATIENTS WITH CROHN’S DISEASE: A RANDOMISED CONTROLLED TRIAL

E. Halmos¹, C. Christophersen², A. Bird², S. Shepherd¹, J. Muir¹, P. Gibson¹

¹Monash University, Melbourne, ²CSIRO, Adelaide, Australia

Contact E-mail Address: Peter.Gibson@monash.edu

Introduction: A low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet is commonly used in patients with Crohn’s disease and functional gut symptoms, however, its putative negative effects on microbiota¹ is concerning in a population at high risk of dysbiosis.

Aims & Methods: This study aimed to investigate the effects of altering FODMAP intake on markers of colonic health in patients with Crohn’s disease. Nine patients with clinically quiescent Crohn’s disease underwent evaluation of their habitual diet followed by randomisation to 21 days of provided diets containing low or typical amounts of FODMAPs (‘Australian diet’) and matched for other nutrients in a cross-over design with >21-day washout. Five-day faecal samples were collected and pooled during each diet and analysed for calprotectin, pH, short-chain fatty acids (SCFA) and bacterial abundance. Gastrointestinal symptoms were recorded daily using 0-100mm visual analogue scale.

Results: Eight participants collected faeces and were adherent to the diets. FODMAP intake differed across the 3 diets with mean daily oligosaccharide and polyol content 1.8g on low FODMAP, 4.8g on habitual (lower than previous estimations of typical intake) and 9.7g on Australian diet. Calprotectin, SCFA, pH, and total bacterial abundance remained unaltered, but the Australian diet increased relative abundance of butyrate-producing Clostridium cluster XIVa by 7-fold and mucus-associated Akkermansia muciniphila by 10-fold compared to the other diets and reduced Ruminococcus torques compared to the low FODMAP diet (Table). These changes were similar to a similarly studied IBS/healthy cohort¹. Symptoms were increased by the Australian diet (mean[95%CI] 24.8 [12.6-37]mm compared to low FODMAP 13.5 [5.9-21.1]mm and habitual diet 12.5 [8.7-16.3]mm; P < 0.001 repeated measures ANOVA).

Table.

Relative abundance of faeces. Differences between provided diets are shown in bold and between habitual diet indicated with an asterisk (P < 0.05; Wilcoxon matched-pairs signed rank test)

Bacteria	Australian diet	Low FODMAP	P-value	Habitual diet
Clostridium cluster IV	2.70 [0.63-4.78]	2.69 [0.93-4.46]	0.383	3.02 [0.77-5.26]
Faecalibacterium prausnitzii	0.47 [0.21-0.72]	0.66 [0.14-1.19]	0.250	0.81 [0.09-1.54]
Clostridium cluster XIVa	19.2* [11.2-27.3]	2.81 [1.88-3.74]	0.008	2.90 [1.80-4.01]
Roseburia	0.94 [0.21-1.68]	0.81 [0.18-1.44]	1.00	0.68 [0.23-1.13]
Akkermansia muciniphila	0.15* [-0.05-0.35]	0.01 [-0.02-0.04]	0.016	0.01 [-0.01-0.03]
Ruminococcus gnavus	1.17 [-0.25-2.59]	1.39 [-0.38-3.17]	0.461	2.26 [-1.51-6.03]
Ruminococcus torques	0.10 [-0.04-0.24]	0.16 [-0.03-0.34]	0.039	0.15 [-0.05-0.35]

Conclusion: The increase in FODMAPs on the Australian diet induced a prebiotic effect in patients with Crohn’s disease, but increased symptoms. No ‘anti-prebiotic’ effect was seen on a low FODMAP diet compared to the habitual diet, which was lower in FODMAPs than expected. The promotion of increased FODMAPs for gut health may be at the cost of inducing functional symptoms and caution should be taken in reducing FODMAP intake below an estimated typical diet.

Disclosure of Interest: E. Halmos: None declared, C. Christophersen: None declared, A. Bird: None declared, S. Shepherd Conflict with: Published a book on food intolerances and several cookbooks related to the topic, J. Muir: None declared, P. Gibson Conflict with: Published a book on food intolerances

P0594 CHANGES IN GASTRIC AND GALLBLADDER DYNAMICS AFTER A GLUTEN-CONTAINING VERSUS GLUTEN-FREE MEAL: AN ULTRASONOGRAPHIC STUDY

S. Massironi¹, F. Branchi², A. Baccarin², M. Fraquelli¹, D. Conte², M. T. Bardella¹, L. Elli³

¹Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, ²Department of Pathophysiology and Transplantation, Università degli Studi di Milano, ³Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy

Contact E-mail Address: federica.branchi@gmail.com

Introduction: Gluten ingestion has been reported to be involved in a broad spectrum of gastrointestinal symptoms even in absence of a detectable immunologic response. However, data concerning the pathophysiological effects of gluten on the upper gastrointestinal tract are limited.

Aims & Methods: Aim of the study was to assess the effect of gluten ingestion on gastric emptying or gallbladder contraction and relaxation.

Between June and October 2014, 10 healthy subjects underwent ultrasound (Philips iU22, Bothell, WA, USA) evaluation of gastric emptying dynamics and gallbladder contraction at base line and at 30 minutes intervals after a standard solid meal (250 kcal, 70% carbohydrates), until the antral area returned to the basal value. The evaluation was performed in all subjects both after a gluten-containing and a gluten-free meal.

Results: Overall, the pattern of gastric emptying was similar after both types of meal, but differed in terms of postprandial filling peak, which was significantly wider (median area 5.1, range 3.7-7.9 vs 3.7, range 2-6.3 cm^2, p=0.006) after the gluten-containing than the gluten-free meal. Gastric emptying time was longer after the gluten-containing meal (median 225 min, range 90-360 vs 180 min, range 60-230, p=0.2) although this finding did not reach statistical significance. The pattern of gallbladder contraction was different after the gluten-free meal (p < 0.05), with higher gallbladder volumes observed in the late refilling phases.

Conclusion: The present data support the hypothesis of a relevant effect of gluten intake on both gastric and gallbladder motility. Although the underlying pathophysiological mechanism is still unknown, these results could account for some of the gluten related symptoms.

Disclosure of Interest: None declared

MONDAY, OCTOBER 26, 2015   09:00-17:00

PAEDIATRIC: UPPER GI – HALL 7__________

P0595 CYSTIC FIBROSIS CHILDREN WITHOUT GASTROOESOPHAGEAL REFLUX DISEASE HAVE FUNCTIONAL IMPAIRMENT OF OESOPHAGEAL MUCOSA AS DETERMINED BY COMBINED OESOPHAGEAL IMPEDANCE-PH MONITORING

J. Brecelj¹, R. Orel¹

¹Department of Pediatric Gastroenterology, Hepatology and Nutrition, University Children's Hospital, Ljubljana, Slovenia

Contact E-mail Address: jernej.brecelj@gmail.com

Introduction: CF patients are prone to gastrooesophageal reflux disease (GORD). Main pathogenetic mechanism is stronger gastrooesopgaheal reflux during transient lower oesophageal sphincter relaxations due to a larger pressure difference between abdominal and thoracic cavity. It is not clear if there are additional pathogenetic mechanisms apart from gastrooesophageal reflux affecting oesophageal mucosa.

Aims & Methods: The aim of this study was to compare functional parameters measured by combined oesophageal impedance-pH (MII-pH) monitoring in CF patients without GORD with a group of non-CF children without GORD.

The study was retrospective re-analysis of stored MII-pH recordings. In the study group were included children with CF who underwent combined oesophageal impedance-pH (MII-pH) monitoring due to the signs of GORD but had a normal investigation result. As the control group we included children who underwent MII-pH due to extraintestinal symptoms of GORD but who had a normal MII-pH, too. We compared standard MII-pH parameters (No. of acid, weakly acid and non-acid refluxes, total acid exposure index, DeMeester score) and recently proposed additional parameter of epithelial integrity called baseline impedance. Groups were compared with nonparametric Mann-Whitney U test was used (small sample, not-normal data distribution).

Results: We identified 13 children with CF (1-18 y, median age 10 y, 5 males) and 17 children without oesophageal disease (1-15y, median age 8 years, 6 males) who underwent MII-pH (Ohmega measurement system, MMS, Netherlands) between 2009 and 2014 and re-analysed recordings using same analysis strategy. There were no differences between the groups regarding age (p=0.645), weight (p=0.965), height (p=0.908), and body mass index (p=0.447). According to the inclusion criteria, impedance and pH parameters were normal and equally distributed in both groups (No. of acid refluxes (p=0.057), non-acid refluxes (p=0.085), total acid exposure index (p=0.530), DeMeester score (p=0.722)), except from weakly acid refluxes (p=0.011) which were more prevalent in the cystic fibrosis group. The baseline impedance between upper two (Z1; p=0.023) and lower two (Z6; p=0.006) electrodes were significantly lower in CF group.

Conclusion: Despite not having GORD and having the same standard MII-pH parameters except weakly acid refluxes, in the group of children with CF and without GORD we measured lower baseline impedance in Z1 and Z6. This indicates either greater importance of weakly acid refluxes than previously thought or an additional, probably local factor influencing membrane integrity which is reflected in the baseline impedance. The exact pathogenetic mechanism and the importance of this finding have yet to be determined.

Disclosure of Interest: None declared

P0596 HELICOBACTER PYLORI RESISTANCE TO ANTIBIOTICS IN CHILDREN

R. Auzbikiene¹, J. Zalyte¹, J. Kirsliene¹, V. Urbonas²

¹Children‘s Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos, ²Children‘s Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania, Clinic of Childrens’ diseases of Vilnius University Faculty of Medicine, Vilnius, Lithuania

Contact E-mail Address: renata.jakubkaite@gmail.com

Introduction: Increased H. pylori resistance to antibiotics is observed in many countries, especially in children. The amount of antibiotic consumption influences their resistance to microbes (1). Clarithromycin consumption in Lithuania from 2009 to 2014 has increased from 1,375 to 1,514 (the average daily therapeutic dosage/1000 citizens/per day).

Aims & Methods: To evaluate H. pylori primary resistance to antibiotics in children and to compare this data with previous results. H. pylori susceptibility to antibiotics were tested in children to whom H. pylori eradication has not been applied before. From 2013 until 2015 March at tertiary Vilnius University Children‘s Hospital, Lithuania upper gastrointestinal tract endoscopy with antrum biopsies were performed in children with abdominal pain, dyspepsia symptoms or anemia. Biopsies from 137 children (80 girls, 57 boys) with positive urease test were sent for H. pylori micriobiological investigation. Samples were grown microaerobically at 37°C on horse agar. The E-tests were performed for amoxicillin (Amo) (MIC ≥0.125 mg/l), clarithromycin (Cla) (MIC ≥0.5 mg/l), metronidazole (Met) (MIC ≥8 mg/l), levofloxacin (Lev) (MIC ≥1 mg/l).

Results: H. pylori grew in 82 (60.4%) of 137 microbiological samples. Resistance to at least one antibiotic was in 41 (50%) cases. Resistance to Cla in 33 (40.2%) cases, to Met - 18 (22%), to Lev 2 (2,4%). Combination of Cla and Met in 11 (13,4%) cases. No cases of Amo resistance have been detected. We compared this data with the previous study results performed in 2007-2008 in Lithuania (2). The results revealed that resistance to Cla has increased from 16,8% to 40.2% (p < 0.05), to Met - from 20.7% to 22% (p=0.88), resistance to both antibiotics from 4,2% to 13,4% (p=0.089).

Conclusion: 1. From 2007-2008 to 2013-2015 H. pylori resistance to Cla has increased 2,4 times and to Met increase was statistically not significant. Resistance to Lev was observed in isolated cases.

2. The increased resistance to Cla could be associated with increased consumption of Cla in the country.

Disclosure of Interest: None declared

P0597 PECULIARITIES OF IRON DEFICIENCY ANEMIA ASSOCIATED WITH HELICOBACTER PYLORI INFECTION IN CHILDREN

M. Gurova¹, V. Novikova²

¹Department of Pediatrics, Belgorod State National Research University, Belgorod, ²Department of Pediatrics, Federal Centre of the Head, Blood and Endocrinology named after V.A. Almazov, Saint-Petersburg, Russian Federation

Contact E-mail Address: itely@mail.ru

Introduction: Iron deficiency anemia (IDA) is the most common nutritional disorder in children, but little information is available about peculiarities of course of the IDA and approaches in treatment in children with Helicobacter pylori (Hp) infection.

Aims & Methods: This study is aimed at assessing the role of Helicobacter pylori infection in children with iron deficiency anemia and effectiveness of the eradication of Hp in treatment of IDA.

For this purpose were examined 67 children with IDA aged 11-15 years, separated into 2 groups: 22 children Hp (+) (1^st group) and 45 Hp (-) children (2^nd group). Diagnosis of IDA was based on follow parameters: level of Hb, RBC, MCV, RDW, serum iron and ferritin level. Presence of Hp was confirmed by rapid urease test and/or gastric biopsy. As eradication therapy patients received 10 days of triple therapy (proton pump inhibitor plus amoxicillin and nifuratel in age dependent dosages).

Results: Hp was found in every third children with IDA. Initial ferritin and Hb level was lower in children with Hp infection (9.4 ± 0.1 g/dl vs 10.6± 0.47 g/dl, P < 0.001; 87.4± 10.56ng/ml vs 118.12 ± 16.38 ng/ml, P < 0.001). In this group IDA had refractory course of the disease and not respond on the basis treatment of IDA compare with children of the 2^nd group. The level of Hb in 1 month after using of iron supplementation wasn’t changed compare with the 2^nd group (increase in Hb > 4 g%). Successful eradication was received in 81.8% children with Hp infection. In 1 month after eradication and basis therapy the mean Hb level was increased more than 4 g/% in 52.9% children, more than 2 g/% in 29.4%, the rest – less than 2 g/%.

Conclusion: H. pylori infection was found in 32.8 % children with IDA. In this group of children anemia characterized by refractory course of disease, lower level of Hb and ferritin compared to children without Hp infection. After successful eradication of H. pylori infection in children with IDA significantly increase the level of Hb.

Disclosure of Interest: None declared

P0598 MUCOSAL MORPHOMETRY AND INFLAMMATION OF DUODENAL BULB BIOPSIES IN COELIAC DISEASE

A. Popp¹², J. Taavela¹, M.-L. Lähdeaho¹, P. Hiltunen¹, T. Ruska¹, I. Anca², M. Mäki¹, K. Kurppa¹

¹Tampere Centre for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland, ²Pediatrics, Institute for Mother and Child Care, Bucharest, Romania

Contact E-mail Address: Alina.Popp@uta.fi

Introduction: Recent coeliac disease guidelines recommend including duodenal bulb specimens in the diagnostic evaluation. However, previous studies exploring the value of bulb in diagnostics have shown inconsistent results. Further, clinical experience suggest that bulb might be more difficult to interpret than distal duodenum due to inferior specimens and differences in the mucosal morphology. We addressed these issues in a prospective pediatric cohort with our validated histological methods.

Aims & Methods: 133 consecutive children with positive serum transglutaminase 2 (TG2) and/or endomysial antibodies were evaluated in clinical centers in Finland and Romania. Upon gastrointestinal endoscopy 6-8 biopsies were taken from anatomic duodenal bulb and distal duodenum irrespective of the macroscopic findings. Special attention was devoted to representative biopsies and correct orientation and cutting of the paraffin-embedded specimens. Quantitative villous height: crypt depth (VH:CrD) ratio was used for the morphometric measurements (normal ratio >2.0). Further, density of mucosal CD3+ and γδ+ intraepithelial lymphocytes (IEL) and presence of TG2 targeted IgA-deposits were evaluated in frozen mucosal samples.

Results: Altogether 118 (88%) out of the 115 children had diagnostic mucosal lesion in at least one biopsy site (median age 7 years, range 1.6 -17.9, 67% girls). Although several samples were taken, in 45% of the patients the bulb specimens were of inadequate quality for accurate morphometric measurements; altogether reliable evaluation was possible from both bulb and duodenum biopsies in only 75 (63%) patients. Four patients (3.4%) showed mucosal damage only in bulb specimens and 3 (2.5%) only in the distal duodenal specimens. There was no significant difference in the mean VH:CrD ratio between the bulb and duodenum (0.4 vs 0.6, p=0.281) but the crypts were deeper in bulb (p=0.020). Also, no differences were observed in the mean density of either CD3 + IELs (76.5 vs 70 cells/mm, p=0.678) or γδ+ IELs (23.6 vs 23.3 cells/mm, p=0.339) between the bulb and duodenum. All coeliac disease patients showed TG2 targeted mucosal IgA deposits in both bulb and distal duodenum samples.

Conclusion: We confirmed previous observations that coeliac patients may have lesions only in the duodenal bulb. However, diagnosis based solely on bulb histology should be used with caution because the samples are often more difficult to interpret and may also differ morphologically from the distal duodenum. Markers of mucosal inflammation and coeliac disease-specific IgA deposits are valuable in both biopsy sites. p=0.020). Also, no differences were observed in the mean density of either CD3 + IELs (76.5 vs 70 cells/mm, p=0.678) or γδ+ IELs (23.6 vs 23.3 cells/mm, p=0.339) between the bulb and duodenum. All coeliac disease patients showed TG2 targeted mucosal IgA deposits in both bulb and distal duodenum samples.

Disclosure of Interest: None declared

P0600 HOW VALUABLE IS “10-TIME ULN THRESHOLD” FOR IDENTIFYING VILLOUS ATROPHY IN SCREENING-DETECTED PATIENTS?

C. M. Trovato¹, M. Montuori¹, R. Nenna¹, F. Valitutti¹, P. De Luca¹, C. Tiberti¹, D. Iorfida¹, F. Lucantoni¹, L. Petrarca¹, M. Mennini¹, C. A. Anania¹, M. Bonamico¹, S. Cucchiara¹

¹Sapienza University, Rome, Italy

Contact E-mail Address: chiaramaria.trovato@uniroma1.it

Introduction: In 2011, the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) has released its updated guidelines on coeliac disease (CD) diagnosis. According to these new guidelines, symptomatic children with anti-transglutaminase (anti-tTG) antibody levels ≥ 10 times upper limit normal (ULN) coul avoid duodenal biopsies if the HLA test and serum anti-endomysial antibodies (EMA) are positive. So far, both symptomatic patients with anti-tTG2 titer <10 times ULN and those asymptomatic should undergo upper endoscopy with “multiple” duodenal biopsies to confirm a suspected CD.

Aims & Methods: The aim of the study was to calculate the positive predictive value (PPV) of anti-tTG levels ≥ 10 ULN in discovering a severe mucosal damage in asymptomatic children, identified by salivary screening. From March 2007 to February 2014, 11698 children (age range: 5-10-years) were enrolled in Rome and Civitavecchia. A total of 8871 salivary samples were collected and tested for anti-tTG, using a fluid-phase radioimmunoassay (RIA). Salivary anti-tTG-positive children were analyzed for serum antibodies (EMA and enzyme-linked immunosorbent assay (ELISA) anti-tTG). Positive children underwent upper gastrointestinal endoscopy; histological lesions were graded according to the Marsh-Oberhuber (MO) criteria.

Results: Among the 8871 screened children, 68 (0.76%) had positive anti-tTG antibodies both in serum and salivary samples. Among them, 57 (83.82%) had anti-tTG titers ≥ 10 times ULN; of these, 56 (98.24%) showed severe lesion degree (3a, 3b, 3c MO) and 1 (1.75%) received a diagnosis of potential CD (MO1). On the contrary, 11 out of 68 (16.17%) children had anti-tTG titers < 10 times ULN; 10 (90.90%) of them had severe mucosal damage (3a,3b, 3c MO) and 1 (9.09%) was classified as potential CD patient (MO 0).These results suggest that anti-tTG ≥ 10 times ULN are remarkably reliable of severe histological damage in asymptomatic children (PPV= 98.2% CI: 90.0%>100%)

Conclusion: If proved in larger and multi center studies, our results suggest the possibility to apply the “biopsy-sparing” protocol also in asymptomatic patients with anti-tTG titer ≥10 times ULN.

Disclosure of Interest: None declared

P0601 SOLUBLE SYNDECAN-1: A POTENTIAL NOVEL BIOMARKER OF SMALL BOWEL MUCOSAL DAMAGE IN CHILDREN WITH CELIAC DISEASE

D. Yablecovitch¹, A. Oren², S. Ben-Horin¹, E. Fudim¹, R. Eliakim¹, F. M. Konikoff³, U. Kopylov¹, A. Lerner⁴

¹Gastroenterology, Chaim Sheba Medical Center, Ramat Gan, ²Pediatric Endocrinology and Diabetes, Tel Aviv Medical Center, Tel aviv, ³Gastroenterology, Meir Medical Center, Kfar Saba, ⁴Pediatric Gastroenterology and Nutrition Unit, Carmel Medical Center, Haifa, Israel

Contact E-mail Address: doronyab@gmail.com

Introduction: Syndecan-1 (SDC1) is essential for maintaining normal epithelial barrier. Shedding of SDC1 ectodomain, reflected by serum soluble syndecan-1(SSDC1) levels, is highly regulated by inflammation. Increased intestinal permeability plays a central role in celiac disease (CD). The association between SSDC1 level and mucosal damage in CD has not been evaluated.

Aims & Methods: Our objectives were to compare serum levels of SSDC1 in children with CD to healthy controls and to determine its relationship with histological grading classified by modified Marsh criteria.

Cross-sectional, pilot study, in which serum concentrations of SSDC1 were analyzed by ELISA in a cohort of 50 consecutive untreated children with CD, 11 children with latent CD and 11 healthy controls. CD was diagnosed based on positive celiac serology and classical small intestinal histology. SSDC1 levels at the day of biopsy were compared with the intestinal damage of the biopsy.

Results: SSDC1 levels were significantly higher in pediatric CD, compared to healthy controls (107.2 ± 150 vs. 44.5 ± 21.1 ng/ml, respectively, p < 0.01). SSDC1 levels were significantly higher in patients with Marsh 3c lesion compared to patients with latent celiac (153.1 ± 186.9 vs. 48.9 ± 34.6 ng/ml, respectively, p <0.05). SSDC1 concentrations correlated significantly with mucosal injury defined by Marsh (r=0.28, p=0.027).

Conclusion: This is the first study demonstrating elevated levels of serum SSDC1 in patients with celiac disease compare to healthy controls. Our results suggest that SSDC1 is a potentially novel marker of intestinal mucosal damage in patients with CD. Its applicability as a diagnostic and a surrogate biomarker in CD remains to be determined.

Disclosure of Interest: None declared

P0602 DIAGNOSIS OF COELIAC DISEASE AMONG CHILDREN WHOSE MOTHERS HAVE COELIAC DISEASE: A UNITED KINGDOM GENERAL POPULATION-BASED COHORT

L. J. Tata¹, F. Zingone¹², K. M. Fleming¹, T. R. Card¹, C. J. Crooks¹, C. Ciacci², J. West¹

¹Division of Epidemiology and Public Health, University of Nottingham, Nottingham, United Kingdom, ²Department of Medicine and Surgery, University of Salerno, Salerno, Italy

Contact E-mail Address: Laila.Tata@nottingham.ac.uk

Introduction: Our aim was to quantify the risk of clinically diagnosed coeliac disease (CD) in children of mothers with coeliac disease to assess this burden in the general population of the United Kingdom.

Aims & Methods: We used a large population-based general practice database (The Health Improvement Network) to obtain data pertaining to all children born between 1990 and 2010 registered with general practices whose records were linked to their mothers’ medical records. We identified all mothers and children diagnosed with CD and assessed the maternal-child CD association using logistic regression with generalised estimating equation modelling, adjusting for potential confounders.

Results: There were 708 children diagnosed with CD in the study population of 798,343 children up to 16 years of age. Among children with CD, 10.3% had mothers who also had CD whereas maternal CD diagnoses were 0.3% among the children without CD. This equated to offspring CD risks of 3.2% versus 0.1% among mothers with CD versus those without. The odds ratio for offspring CD associated with maternal CD was 36.7, 95% confidence interval 28.2-47.7 after adjusting for child sex, socioeconomic deprivation, year of birth, caesarean delivery, and maternal age.

Conclusion: A child born to a woman with CD is almost 40 times more likely to be diagnosed with CD than if the mother does not have CD. In absolute terms, 3.1% more children will receive a diagnosis, considerably raised from the average population risk. This could be due to genetics, shared environmental risk factors within families or ascertainment bias.

Disclosure of Interest: None declared

P0603 GUT MICROBIOTA IN CELIAC DISEASE PATIENTS AND ITS CORRELATION WITH SYMPTOMS

G. Marasco¹, A. R. Di Biase², A. Colecchia¹, R. Schiumerini¹, E. Biagi³, P. Brigidi³, D. Festi¹

¹Department of Medical and Surgical Sciences, University of Bologna, Bologna, ²Department of Pediatrics, University of Modena, Modena, ³Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy

Contact E-mail Address: giovanni.marasco4@unibo.it

Introduction: The inflammatory response in celiac disease (CD) is mediated by mechanisms of adaptive immunity and of innate immunity. The activation of the innate immunity takes place by the binding of toll-like receptor (TLR). The inflammatory response is generated only with the initial activation of innate immunity. In CD patients an increased expression of TLR was also found. The intestinal microbiota regulates the intestinal immune system homeostasis through TLR. Recent researches have shown an altered gut microbiota in CD patients compared with healthy controls (HC). On these basis a role of gut microbiota in the pathogenesis of CD and of its symptoms has been hypothesized.

Aims & Methods: To evaluate the composition of the microbiota on duodenal biopsy of CD patients, to compare CD patient faecal microbiota with that of HC and to correlate clinical data with bacterial levels in CD patients.

Subjects were enrolled as outpatients from Pediatric Gastroenterology Unit referring suspected symptoms for CD. At enrolment a sampling of stool and, in patients with suspected CD, of a fragment of the duodenal mucosa during upper endoscopy was performed. Microbiota evaluation was performed by HTF-Microbi.Array ^1-2.

Results: Thirty-two (32) subjects enrolled: 21 CD patients and 11 HC. HTF-Microbi.Array of duodenal biopsy specimen revealed a total dominance of Enterobacteriaceae in CD patient biopsies (in 50% of samples belonging to the genus Proteus) and a subdominance of Bacteroidetes and/or Streptococcus. In stools there was a significantly greater abundance of the cluster of Lactobacillaceae (p < 0.01) and Streptococcaceae (p < 0.02) and a lower abundance of Bacteroides-Prevotella cluster (p < 0.01), Akkermansia (p < 0.01) and Staphylococcaceae (p < 0.01) in CD patients compared to HC. Correlating clinical data with faecal bacterial abundance, an inverse correlation was found between Clostridium cluster XIVa and the presence of diarrhea (p=0.04) and the presence of growth failure (p < 0.02). Diarrhea was directly associated with Clostridium cluster IX (p < 0.01), Bacillaceae (p=0.03) and of Fusobacterium (p < 0.05). The presence of abdominal pain was associated with the abundance of Bacillaceae (p < 0.01) and of Enterobacteriaceae (p=0.01). Furthermore, the abundance of Enterobacteriaceae was associated with IgA anti-tTG antibody levels(p < 0.05).

Conclusion: The intestinal microbiota of CD patients is different from that of HC. In CD there is a particular abundance of potentially pathogenic species such as Enterobacteriaceae and Streptococcaceae. A depletion of Akkermansia, which has a mucosal barrier-protective function and a decrease of Bacteroides-Prevotella, which has an immunomodulatory function, has been demonstrated in CD patients. Moreover, the presence of gastrointestinal symptoms was associated with a decrease of ‘healthy’ species and an increase in potentially harmful species.

Disclosure of Interest: None declared

P0604 HIGH PREVALENCE OF COELIAC DISEASE AMONG PRE-SCHOOL CHILDREN IN VAS COUNTY, HUNGARY

G. Oroszlan¹, M. Balogh¹, J. Dolinšek², J. Dolinšek³, D. Mičetić-Turk⁴

¹Paediatric Department, Markusovszky University Teaching Hospital, Szombathely, Hungary, ²Project Office, Municipality of Maribor, ³Department of Paediatrics, Gastroenterology Unit, University Medical Centre, ⁴Medical Faculty, Department of Paediatrics, University of Maribor, Maribor, Slovenia

Contact E-mail Address: orogyor@gmail.com

Introduction: Celiac disease (CD) remains underestimated in many regions of Europe. Rapid point-of-care tests (POCT) have been previously described to enable detection of new cases at primary care or community-based screening studies.

Aims & Methods: It was our aim to evaluate the prevalence of CD in pre-school children in Vas County in SW Hungary.

1062 pre-school children (age 6-7 years, 462 girls) from 25 kindergartens in Vas County were invited to participate in CD screening using commercially available rapid finger prick test for detection of CD specific antibodies in capillary blood. 62 parents refused testing. All children tested positive and all IgA deficient children were referred for further confirmatory tests to Vas county teaching hospital. Tissue transglutaminase antibodies ELISA based serological tests and total IgA determination was performed and all children also were offered intestinal biopsy to confirm CD.

This study was a part of LQ-CELIAC project partially EU financed by the Operational Programme of Cross-border Cooperation Slovenia-Hungary.

Results: Among 1000 tested children 19 (1.9%) were detected positive with rapid test and another 9 (0.9%) were IgA deficient. Among positive children 7 (43%) had unspecific gastrointestinal symptoms. They had not been tested for CD previously. The remaining 12 positive children were asymptomatic.

CD was confirmed serologically and histological in 16 children (1.6%). Serology was negative in two positive children, and in one histology was negative. This child was HLA DQ2 positive. All three will be further followed.

Conclusion: Rapid testing for CD in young children in Vas County in Hungary has detected unexpectedly high number of affected children, with figures similar to those from a previous study in Jasz-Nagkykun-Szolnok County in Hungary. To our surprise almost half of detected children were symptomatic, and could have been detected earlier.

Rapid testing for CD has shown to be a valuable tool for community-based screening even in young children. At the same time the awareness about CD must increase in order to detect symptomatic children before the onset of preventable complications of the disease.

Disclosure of Interest: None declared

P0605 PRIMARY PREVENTION OF TYPE-1 DIABETES MELLITUS BY CHILDHOOD MASS SCREENING FOR COELIAC DISEASE

I. R. Korponay-Szabo¹², K. Szabados³, J. Pusztai⁴, É. Rózsáné. Rigó⁴, H. Hyöty⁵, M. Mäki⁶, on behalf of The nPOD Study Group

¹Dept. of Paediatrics, University of Debrecen, Debrecen, ²Coeliac Disease Centre, Heim Pál Children's Hospital, Budapest, ³Hetényi Géza County Hospital, ⁴Jász-Nagykun-Szolnok County Public Health Office and Local Governmental District Nurse Services, Szolnok, Hungary, ⁵Dept. of Virology, ⁶Tampere Center for Child Health Research, University of Tampere Medical School, Tampere, Finland

Contact E-mail Address: Ilma.Korponay-Szabo@uta.fi

Introduction: Coeliac disease and type-1 diabetes mellitus (T1D) are often associated but a causative relationship is not yet confirmed.

Aims & Methods: Aim of this study was a prospective intervention to investigate whether undetected coeliac disease can cause T1D diabetes mellitus. The prevalence of T1D was studied in 2014 in a county among schoolchildren (n=21724) in five school year birth cohorts born between 1.6.1996 and 31.5.2001 using local school nurse registries and data from diabetes centres. The middle birth cohort born between 1.6.1998-31.5.1999 received screening for anti-transglutaminase and anti-endomysial antibodies in 2005, at the age of 6 years (BMJ 2007;335:1244-7), where 78% of the total population took part. Screen-detected coeliac disease cases were confirmed by small bowel biopsy, treated by a gluten-free diet and followed by regular serology monitoring at the local gastroenterology unit. The screened and not screened children used the same schools and were exposed to identical other environmental factors.

Results: None of the screen-detected & treated coeliac cases (n=45) developed T1D. The prevalence of T1D was 2.69/1000 children (95% confidence intervals [CI] 1.92-3.46) in the not screened control birth cohorts comprising children 1&2 years older as well as 1&2 years younger than the screened cohort. The prevalence of T1D was 0.93/1000 children (95% CI 0.02-1.85) in the screened/treated cohort, odds ratio 0.35 (95% CI (0.13-0.96). Half of the T1D cases in the birth cohort where the screening took place actually did not participate in the screening due to lack of parental consent. Eighty-two percent of all paediatric T1D cases in the population appeared after the age of 6 years.

Conclusion: Early detection and treatment of coeliac disease is able to prevent a substantial fraction of paediatric-onset T1D cases.

Disclosure of Interest: None declared

P0606 A NOVEL MOUSE MODEL FOR MICROVILLUS INCLUSION DISEASE IDENTIFIES A ROLE FOR MYOSIN VB IN APICAL AND BASOLATERAL RECYCLING

K. Schneeberger¹, H. Teunissen¹, D. D. van Ommen²³, H. Begthel⁴, L. El Bouazzaoui¹, A. H. van Vugt¹, J. M. Beekman², J. Klumperman⁵⁶, H. Clevers⁴, J. H. van Es⁴, E. E. Nieuwenhuis¹, S. Middendorp¹

¹Pediatric Gastroenterology, ²Pediatric Pulmonology, ³Lab Translational Immunology, UMC Utrecht, ⁴Hubrecht Institute for Developmental Biology and Stem Cell Research, ⁵Cell Biology, ⁶The Cell Microscopy Centre, UMC Utrecht, Utrecht, Netherlands

Contact E-mail Address: s.middendorp@umcutrecht.nl

Introduction: Microvillus inclusion disease (MVID) is a rare intestinal enteropathy with an onset within a few days to weeks after birth, resulting in persistent watery diarrhoea. Mutations in the myosin Vb (MYO5B) gene have been identified in the majority of MVID patients. However, the exact pathophysiology of MVID still remains unclear.

Aims & Methods: To address the specific role of MYO5B in the intestine we generated and analysed an intestine-specific conditional Myo5b-deficient deficient (Myo5b^fl/fl;Vil-CreERT2) mouse model. We analysed intestinal tissues and cultured organoids of Myo5b^fl/fl;Vil-CreERT2 mice by electron microscopy (EM), immunofluorescence and immunohistochemical methods.

Results: Myo5b^fl/fl;Vil-CreERT2 mice developed severe diarrhoea within 4 days after tamoxifen induction. Periodic Acid Schiff (PAS) and alkaline phosphatase (ALP) staining revealed subapical accumulation of intracellular vesicles in villus enterocytes. Analysis by electron microscopy (EM) showed an almost complete absence of apical microvilli and the appearance of microvillus inclusion bodies in induced Myo5b^fl/fl;Vil-CreERT2 intestines. In addition, we showed that MYO5B is involved in not only apical, but also basolateral recycling of proteins. The analysis of the intestine during the early onset of the disease revealed that subapical accumulation of secretory granules precedes entrapment of recycling endosomes, indicating involvement of MYO5B in early differentiation of epithelial cells.

Conclusion: Our mouse model completely recapitulates the intestinal phenotype of human MVID, including severe diarrhoea, loss of microvilli, microvillus inclusions and accumulation of secretory granules. Our data indicate a novel mechanism for MYO5B in regulating polarity of epithelial cells, which might explain the secretory component of diarrhoea in MVID due to disturbed barrier function. We conclude that loss of MYO5B disturbs both apical and basolateral recycling of proteins and causes MVID.

Disclosure of Interest: None declared

P0607 SYSTEMATIC REVIEW ON FEEDING DISORDERS IN CHILDREN DIAGNOSED WITH AUTISM

G. Veereman¹, N. Fairon¹, K. Holdt Henningsen¹, N. Benahmed¹, W. Christiaens¹, M. Eyssen¹

¹Belgian Health Care Knowledge Center, Brussels, Belgium

Contact E-mail Address: gveereman@gmail.com

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder diagnosed according to defined criteria set out in the DSM-5. Feeding disorders are a major concern of parents caring for children with ASD. Since recent evidence-based guidelines fail to address this issue we conducted a systematic review (SR) on the subject.

Aims & Methods: Medical databases (Medline Ovid and Pubmed, Psychinfo Ovid, Embase & Cochrane) were searched using Mesh terms and keywords referring to ‘autism’ and ‘feeding disorders’ with no time limits. All studies on children, with any study design, were included. We adhered to the PRISMA recommendations.

Results: Four SR and 17 primary studies reached our selection criteria. One SR confirmed the higher prevalence of eating disorders in ASD [1]. Two SRs described selective eating patterns [2, 3]. One meta-analysis was retrieved on treatment outcomes to improve feeding [4]. Additional primary studies were published from 1978 onwards. They reported on diagnosis (n=1), feeding behaviour (n=4), breastfeeding (n=1), nutritional deficiencies (n=5) and feeding programs (n=6).

Conclusion: Despite their frequency, current guidelines fail to address feeding difficulties experienced by children with ASD. Recent SR focus on (behavioural) interventions to improve oral intake in autistic children. Studies on underlying physiological mechanisms, deglutative function, sensory or motor function of the upper gastrointestinal (GI) tract are lacking. Since autism is currently considered a neurodevelopmental disorder it may be advisable to explore GI function.

Disclosure of Interest: None declared

P0608 DIETARY MODIFICATIONS OF THE MATERNAL DIET AMONG BREASTFEEDING MOTHERS

M. Iacovou¹, G. Yelland¹, J. Barrett¹, P. Gibson¹, J. Muir¹

¹Department of Gastroenterology, Monash University, Melbourne, Australia

Contact E-mail Address: marina.iacovou@monash.edu

Introduction: Fussing and colicky infants are challenging to the breastfeeding mother and multiple actions are taken in attempt to improve infant behaviour. One apparently common technique is for mothers to adjust their own habitual diet. Changes instituted have stemmed from ‘old-wives tales’ and popular beliefs. A major concern of dietary change is that nutritional adequacy may be compromised. The frequency and types of manipulation used and the success of such adjustments are poorly documented.

Aims & Methods: To explore the dietary practices of breastfeeding mothers, to define the frequency of dietary change, reasons for such action, and to gauge whether they are at risk of nutritional inadequacy.

An on-line survey was developed using Qualtrics software application. Survey questions were designed to collect both quantitative and qualitative data. The survey was anonymous and volunteers were invited to participate through websites and social media such as Facebook and Twitter.

Results: Of the 1203 respondents, 1,046 (87%) completed the survey. 780 (75%) modified their usual diet while breastfeeding. The most common reasons were ‘baby was unsettled’ (33%), ‘baby had lots of wind/gas’ (29%), ‘baby wasn’t sleeping well’ (18%), ‘baby had reflux’ (18%) and ‘baby had colic’ (11%). The most common dietary modifications were minimisation of the intake of alcohol (79%), coffee (43%), cow’s milk (24%), milk chocolate (21%), and cabbage, chilli and onion (each 20%). Information was sourced from the internet (46%), maternal and child health nurses (44%), the Australian Breastfeeding Association (37%), and books and mother’s groups (each 21%). Sourcing information from paediatricians was less common (9%) and 89% of respondents who had modified their diet had never seen a dietitian. 25% of respondents who had removed dairy did not replace it with other calcium-rich foods nor did they take a calcium supplement. 44% that modified their diet did not take a suggested breastfeeding multi-vitamin for when the nutrition guidelines are difficult to meet.

Conclusion: Dietary modification among breastfeeding mothers is common practice (3 out of four) and a variety of food and drink sources are avoided placing them at risk of deficiencies such as calcium. This together with the fact that the majority of information is sourced from the internet and not experts in nutrition suggest this group is at risk of nutritional inadequacies in general.

Disclosure of Interest: None declared

P0609 MANIPULATING THE DIET OF BREASTFEEDING MOTHERS TO RELIEVE THE SYMPTOMS OF INFANTILE COLIC: A PROOF OF CONCEPT STUDY

M. Iacovou¹, E. Mulcahy¹, H. Truby², J. Barrett¹, P. Gibson¹, J. Muir¹

¹Department of Gastroenterology, ²Department of Nutrition and Dietetics, Monash University, Melbourne, Australia

Contact E-mail Address: marina.iacovou@monash.edu

Introduction: Infantile colic is the most common complaint for which parents seek professional advice during the first months of life, and occurs in both breastfed and formula-fed infants. Mothers are often advised to avoid certain ‘gas-forming’ foods (e.g., onions or legumes) although the scientific evidence supporting this advice is poor. A recent placebo-controlled study of probiotics showed a mean improvement of 49 minutes over one month, in symptoms of infantile colic (cry-fuss) in both arms. Anecdotal reports of relief of infantile colic when the mother reduced dietary FODMAPs (Fermentable Oligo- Di- and Mono-saccharides And Polyols) have been received by our group. The low FODMAP diet is known to reduce bloating and abdominal pain in adults with irritable bowel syndrome. This prompted our assessment of the concept that maternal low FODMAP diet might be efficacious for infantile colic.

Aims & Methods: To perform a proof-of-concept study of the effect of a low FODMAP diet in breastfeeding mothers, on the behaviour of their infants with colic.

An open-label study of infants with colic, as defined by the Wessel Criteria, was undertaken. Mothers, who were exclusively breastfeeding, were supplied with a low FODMAP diet for seven days. Using the validated Barr diary, the behavioural patterns of infants were captured for seven days at baseline and daily during the dietary intervention. The mothers were followed for 14 days.

Results: 18 infants, aged 2-16 weeks (mean 8 weeks), were studied. The mothers were aged 29-40 y (mean 34 y), 85% of mothers with the first child. The duration of crying times reduced from mean (SD) of 142 (70) to 90 (60) min/d representing a reduction of 35% (p=0.0001; paired t-test). Crying episodes reduced from 12 (5) to 8 (4) per day, a reduction of 33 % (p=0.0018) and crying-fussing time combined reduced from 232 (69) to 161 (56) min/d, a reduction of 31% or 71 mins (p=0.0006). In the weeks following the intervention, 16 mothers continued on a low FODMAP diet.

Conclusion: Consuming a low FODMAP diet was associated with a reduction of infantile colic that was greater than the anticipated clinical significance of >25%, as deemed by previous colic studies. Since infantile colic does spontaneously improve with time, a controlled evaluation of the low FODMAP diet in mothers is needed and mechanisms by which such an effect might occur require investigation.

Disclosure of Interest: None declared

P0610 THE ROLE OF TNF ALFA 308 A/G GENE POLYMORPHISMS IN NUTRITIONAL DISORDERS OF CHILDREN

O. I. Marginean¹, C. Banescu², C. Duicu¹, A. M. Pitea¹, M. O. Marginean¹, C. Marginean³

¹Pediatrics I, ²Genetics, ³Medicine, Medicine University Targu Mures, Targu Mures, Romania

Contact E-mail Address: marginean.oana@gmail.com

Introduction: Obesity and malnutrition are diseases with increasing incidence lately, they becoming important health problems. Multiple factors proved that these two impair growth, an important role being played by inflammation, as well as by the inadequate nutritional intake. Inflammation, anorexia and weight loss are all manifestations of the circulating TNF-alfa. On the other hand, the adipocytes secrete hormones, growth factors, prostaglandins, pro-inflammatory cytokines, among which, the tumor necrosis factor (TNF) -α that has a pro-inflammatory effect.

Aims & Methods: The aim of the current study was to establish the role of TNF alfa 308 G/A gene in the determination of nutritional diseases such as obesity and malnutrition in child, and to establish the correlations between the polymorphisms of the gene TNF alfa 308 and antropometric and laboratory parameters.

Methods: We assessed 290 hospitalized children regarding TNF alfa 308 A/G polymorphisms, anthropometric parameters (mid-upper arm circumference /MUAC and tricipital skin fold thickness/TST), which we correlated with the laboratory findings (proteins). The patients were divided according to their nutritional status into three groups: control group (I) 112 children with normal nutritional status, the group of malnourished children, 100 children (II) and the group of obese children (III) 78 children.

Results: We observed that the genotype GG and GA of the TNF alfa 308 gene was more frequent in the malnourished group [(p=0.01, OR 1.73, 95% CI (1.28-2.36)], while the genotype GG was more frequent in the obese group (p = 0.01, OR 2.21, 95% CI (1.37-4.40). The G allele is also more frequent in the malnutrition group (p = 0.02) BMI, MUAC and TST were significantly correlated with the genotypes GG and GA of the TNF alfa 308 gene (p = 0.001), in malnutrition group (p = 0.01). The same correlation was found for the low serum albumin levels. Serum TNF alfa was correlated with the TNF alfa 308 gene polymorphism in the case of the malnourished children group for genotypes GG (p = 0.02) and GA (p = 0.001), while serum IL 6 was correlated with TNF alfa 308 gene polymorphism in case of genotype GG (p = 0.001).

Conclusion: TNF alfa 308 is an important parameter of inflammation, correlated with nutritional disorders. Malnutrition is more frequently encountered in children who have the GG and GA genotype of the TNF alfa 308 gene, while GG genotype is correlated with obese group inclusively with the form of severe obesity.

Disclosure of Interest: None declared

MONDAY, OCTOBER 26, 2015   09:00-17:00

ADVANCES IN GI SCIENCE USING OMIC TECHNOLOGIES – HALL 7__________

P0611 TCAB1 MUTATIONS ARE ASSOCIATED WITH AN ACCELERATED PROGRESSION OF LIVER CIRRHOSIS

D. Hartmann¹, D. Klein-Kronbeck¹, G. von Figura², A. Kleger³, P. Strnad⁴, H. Friess¹, J. G. D'Haese¹, G. O. Ceyhan¹

¹Department of Surgery, ²Department of Internal Medicine II, Technische Universität München, Munich, ³Department of Internal Medicine I, University of Ulm, Ulm, ⁴Department of Internal Medicine III, RWTH University Hospital Aachen, Aachen, Germany

Contact E-mail Address: daniel.hartmann@tum.de

Introduction: Telomerase Cajal body protein 1 (TCAB1) is a stable component of the telomerase holoenzyme that plays a major role in telomere synthesis. TCAB1 missense mutations have recently been shown to cause dyskeratosis congenita by the disruption of telomerase trafficking. Whether TCAB1 mutations are associated with liver cirrhosis formation is currently unknown and the hypothesis of the present study.

Aims & Methods: The TCAB1 gene was sequenced in 144 individuals (48 patients with hepatitis C-induced cirrhosis, 48 patients with alcohol-induced cirrhosis and 48 non-cirrhotic controls). In total, 3.744 DNA sequences were analysed and compared to the wildtype TCAB1 form in order to determine the incidence of mutations. Patients with nucleotide variants within the TCAB 1 gene were screened for demographic and clinical characteristics, such as progression of disease, overall survival or tumorigenesis.

Results: We detected 9 different nucleotide variants within the TCAB1 gene, including a newly identified c.663G > A p.V221V mutation in the group of hepatitis C-induced cirrhotics (allele frequency 0.010). The frequency of single nucleotide polymorphisms in African patients was significantly increased compared to Caucasian patients (p value <0.0001). Furthermore, the group of homozygote mutation carriers in the alcohol-induced cirrhosis group was found to significantly correlate with a more rapid progression of liver cirrhosis (p value 0.0139). Survival data of this group showed a significant correlation between the presence of homozygote TCAB1 nucleotide variants and liver failure (p value 0.0352).

Conclusion: Taken together, these data provide the first experimental evidence that TCAB1 gene mutations are present in a subset of liver cirrhosis patients. Furthermore, we were able to show that TCAB1 mutations lead to an accelerated cirrhosis formation in chronic liver disease and a decreased survival of affected patients with alcohol-induced liver cirrhosis. These data provide a potential starting point for the development of new therapeutic strategies for the treatment or prevention of liver cirrhosis.

Disclosure of Interest: None declared

P0612 AN EVIDENCE-BASED SOFTWARE TOOL FOR PERSONALIZED CANCER MEDICINE TO RECOMMEND THERAPEUTIC OPTIONS AND AVOID TOXICITY

M. Löhr¹, K. Stecker², C. Huelsewig², S. Morandell², L. Malgerud¹, C. F. Moro³, M. Karimi⁴, J. Permert⁵, R. L. Heuchel¹, J. Lindberg⁶, V. Wirta⁷, A. Picker², M. Del Chiaro¹, S. L. Haas⁸, C. S. Verbeke³, L. Engstrand⁷, J. Siveke⁹, D. Jackson², H. Grönberg⁶, D. Jäger¹⁰, S. Brock²

¹CLINTEC/Gastrocentrum K53, Karolinska Institutet & Universitetssjukhus, Stockholm, Sweden, ²Molecular Health GmbH, Heidelberg, Germany, ³Dept. of Pathology, ⁴Dept. of Oncology, ⁵Innovation Office, Karolinska Institutet & Universitetssjukhus, ⁶Dept. of Medical Epidemiology and Biostatistics, Karolinska Institutet, ⁷Clinical Genetics, Science for Life Laboratory, ⁸Karolinska Institutet & Universitetssjukhus, Stockholm, Sweden, ⁹Dept. of Medicine, RHCC, Technical University Munich, München, ¹⁰National Center for Tumors, Univ. of Heidelberg, Heidelberg, Germany

Contact E-mail Address: matthias.lohr@ki.se

Introduction: For many tumors, therapy is sparse beyond the guidelines. More treatment relevant biomarkers are known for targeted therapy. DNA analysis with next generation sequencing (NGS) is becoming a routine. However, to analyse the vast amount of data and provide concrete, evidence-based treatment recommendations is a challenge.

Aims & Methods: To demonstrate the feasibility of personalised cancer medicine by applying NGS in a quality controlled set-up together with the newly developed evidence-based software tool TreatmentMAP (CE-marked).

Results: From Oct 2013 to April 2015, 51 patients were analysed with TreatmentMAP. In 4 cases, more than one tumor was investigated. NGS was performed (WXS = 33; panel/paired = 15, panel = 3). Sequencing could be performed in all but one patient (Whole Exome; bone metastasis). Sequencing quality was insufficient for analysis in 3 cases (paired panel), leaving 47 patients. The indication was: Pancreatic = 20; Colorectal = 10; Breast = 3; CUP = 2; NSCLC = 2; and 1 case each for Adenocarcinoma, Common Bile Duct, Endometrial, Glioblastoma, Liver, Lung, Leukemia, B-Cell Lymphoma, Mantle-Cell Lymphoma, Meningioma, Multiple Myeloma, Prostatic, Sigmoid, Uveal melanoma.

In 44/47 patients, drugable targets (response biomarkers) could be identified (range 0-8; median 3). In 28/47 patients (range 0-5; median 1) biomarkers indicated lack of efficacy (e.g. KRAS mutation in CRC). In 42/47 patients, biomarkers indicated increased toxicity (range 0-7; median 2), in 14/42 patients FDA-approved biomarkers for toxicity were detected (22 biomarkers).

Of the positive biomarkers, 32 biomarkers in 20 patients indicated drugs approved in the indication, 55 biomarkers in 29 patients indicated approved drugs, and 44 biomarkers in 28 patients indicated experimental drugs (pre-clinical and phase II - III). Six patients have already received drugs recommended by TreatmentMAP. In 9 patients, toxicity markers explained observed toxicity during previous treatment.

Conclusion: In 93 of the evaluable patients, at least one drugable target could be identified using this evidence-based software. In less than 50% of the patients, these were approved in the indication. In 89% of the cases, a biomarker indicating increased toxicity was detected, in 20% FDA-approved. In conclusion, application of personalised csancer medicine has to take into account that many drugs approved may not be available for the required indication.

Disclosure of Interest: M. Löhr Financial support for research: Molecular Health, Consultancy: Molecular Health, K. Stecker Conflict with: Molecular Health, C. Huelsewig Conflict with: Molecular Health, S. Morandell Conflict with: Molecular Health, L. Malgerud: None declared, C. Moro: None declared, M. Karimi: None declared, J. Permert: None declared, R. Heuchel: None declared, J. Lindberg: None declared, V. Wirta: None declared, A. Picker Conflict with: Molecular Health, M. Del Chiaro: None declared, S. Haas: None declared, C. Verbeke: None declared, L. Engstrand: None declared, J. Siveke: None declared, D. Jackson Conflict with: Molecular Health, H. Grönberg: None declared, D. Jäger: None declared, S. Brock Conflict with: Molecular Health

P0613 METHYLATION OF NEUROG1 IN SERUM CAN COMPLEMENT THE FECAL IMMUNOCHEMICAL TEST FOR COLORECTAL CANCER SCREENING IN FAMILY-RISK INDIVIDUALS

L. De Chiara¹, O. Otero Estévez¹, J. Cubiella², V. Hernández³, I. Castro², M. Páez de la Cadena¹, F. J. Rodríguez-Berrocal¹, V. S. Martínez-Zorzano¹

¹Bioquímica, Genética e Inmunología, University of Vigo, Vigo, ²Aparato Digestivo, Complexo Hospitalario Universitario de Ourense, Ourense, ³Aparato Digestivo, Complexo Hospitalario Universitario de Vigo, Vigo, Spain

Contact E-mail Address: ldechiara@uvigo.es

Introduction: NEUROG1 (Neurogenin1) is frequently found methylated in colorectal cancer (CRC) and has been included as a criteria to classify tumors as CIMP (CpG island methylator phenotype)^1-2. Individuals with first-degree relatives with CRC are at increased risk for developing advanced neoplasia [AN; CRC and advanced adenomas (AA)]³. Therefore, new non- invasive screening methods for this population are still necessary.

Aims & Methods: To determine the diagnostic yield of NEUROG1 methylation for the detection of AN in asymptomatic individuals with first-degree relatives with CRC. All individuals were recruited from “Complexo Hospitalario de Ourense” and underwent a colonoscopy, a fecal immunochemical test (FIT) and a blood extraction. Methylation of NEUROG1 in serum samples was assessed using pyrosequencing in 33 individuals with no neoplasia, 36 AA and 8 CRC cases (44 AN). The promoter region analyzed included the 12 CpG sites reported by Herbst et al. (2011)⁴ for CRC diagnosis.

Results: Mean methylation levels for each of the 12 CpG sites analyzed were increased in individuals with AN compared to no neoplasia, though no statistically significant differences were found. The area under the curve (AUC) for discriminating AN resulted between 0.467-0.621, with the highest AUCs corresponding to CpG site 7, 8 and 9. Based on this optimal combination the AUC was 0.619 (95% CI 0.491-0.747). Given the importance of a high specificity for a screening test, a sensitivity of 27.3% was reached with a 93.9% specificity for detecting AN.

In relation to FIT (cut-off ≥100 ng/mL), all CRC cases were detected and 33.3% of the AA cases. Among FIT negative individuals, CpG sites 7-9 from NEUROG1 showed an AUC of 0.620 (95% CI 0.474-0.766) for the diagnosis of AA. One-fourth (25%) of the AA not diagnosed by FIT were detected, with a 93.9% specificity (cut-off ≥10.6% methylation).

Conclusion: Methylation analysis of NEUROG1 by pyrosequencing revealed that its diagnostic performance for AN may be maximized including only 3 of the 12 CpG sites (CpG sites 7-9). Based on our study, methylation of NEUROG1 in serum seems valuable to complement FIT for the detection of AA in CRC screening.

Disclosure of Interest: None declared

P0614 A NOVEL SAMPLING METHOD FOR ANALYSIS OF THE HUMAN GUT MICROBIOME

J. Booth¹, A. Llewelyn¹, C. Collins¹

¹Origin Sciences Limited, Cambridge, United Kingdom

Contact E-mail Address: jodie.booth@originsciences.com

Introduction: The gut microbiome is the most complex bacterial community in the human body. Alterations in the composition of intestinal microbiota are associated with various disease states including inflammatory bowel disease, obesity and colon cancer.

The majority of studies of the human gut microbiome have analysed stool samples although mucosal biopsy specimens have also been used in numerous studies. In this study, we investigated the utility of OriCol™, a novel sampling device, for profiling the human gut microbiome.

Aims & Methods: This study was undertaken to compare the microbiome profile collected in human stool, rectal swab and rectal mucosa. The purpose of the study was to examine the differences and relationships in gut microbial abundances using the different sampling techniques, and to validate the degree to which the OriCol™ sampling technique can accurately replicate trends in microbial diversity using stool samples as a microbial reference.

The OriCol™ device is a simple, convenient method for sampling the rectal mucosa without the need for prior fasting or bowel preparation. Sampling can be performed by a trained healthcare professional in less than 5 minutes. The device incorporates a nitrile membrane, which after insertion into the rectum via a standard proctoscope, is inflated to make contact with the rectal mucosa. The membrane is then deflated and retracted into the device prior to removal from the patient. Upon retraction the material sampled from the rectal mucosa is retained on the inverted membrane. The device can either be stored frozen or a suitable buffer added to preserve the material for subsequent analysis.

Samples from the rectal mucosa (obtained using the OriCol™ device) and stool were obtained from 5 healthy volunteers on three discrete occasions. A single rectal swab sample was taken from each volunteer immediately before the final OriCol™ sample. The microbial community of samples was profiled via 16S V4 sequencing.

Results: OriCol™ and stool samples have comparable diversity measures, while samples taken using a rectal swab show lower diversity. Whole microbiome abundance profiles were significantly different between OriCol™ and stool samples when grouped by subject (p < 0.001) or sample type (p < 0.001). These differences were attributable to shifts in abundance rather than the presence or absence of bacteria. Significantly higher levels of Proteobacteria were observed in OriCol™ over stool. The OriCol™ device is able to capture differences between donors, but the microbial community is different to that from stool samples.

Conclusion: The OriCol™ device offers a novel, simple and convenient method for physician-led sampling of the gut microbiome represented in the rectal mucosa. Samples using the OriCol™ device contain the same spectrum of bacteria as stool samples but there are differences in the abundance of certain groups, with mucosal organisms such as Proteobacteria relatively enriched in the OriCol™ samples. We hypothesise that this may be due to the capture of bacteria closer to the mucosa by the OriCol™ device.

Disclosure of Interest: J. Booth Directorship(s): Origin Sciences, A. Llewelyn Shareholder: Origin Sciences, C. Collins: None declared

P0615 MINIMUM CURVILINEARITY: AN INNOVATIVE NONLINEAR MULTIVARIATE ANALYSIS REVEALS PROTON-PUMP-INHIBITOR-RELATED PATTERNS IN GASTRIC METAGENOMIC DATA

C. V. Cannistraci¹, G. Cammarota², G. Ianiro², A. Palladini², F. Paroni Sterbini², S. Bibbò², F. Franceschi², B. Posteraro², L. Masucci², G. Gasbarrini², M. Sanguinetti², A. Gasbarrini²

¹Biomedical Cybernetics Group, Biotechnology Center (BIOTEC), Technische Universität Dresden, Dresden, Germany, Dresden, Germany, ²Gastroenterology and Microbiology, Catholic University, Rome, Italy

Contact E-mail Address: kalokagathos.agon@gmail.com

Introduction: Unsupervised discovery of patterns that segregate groups of samples in omic datasets is a pivotal task that is useful in many metagenomic case-control studies. Principal Component Analysis (PCA) and many other linear multivariate methods are the first resort, routinely used for this purpose (Dinsdale et al, 2013). However, they often lack the ability to reveal complex, nonlinear data patterns.

Aims & Methods: We introduce Minimum Curvilinear Embedding (MCE) - a machine learning for nonlinear multivariate analysis (Cannistraci et al, 2010) - in order to detect complex patterns in metagenomic data. Minimum Curvilinearity (MC), the principle behind MCE, suggests that curvilinear distances between samples (e.g. case-control individuals) can be estimated as pairwise distances over their Minimum Spanning Tree (MST), constructed according to a selected norm (Euclidean, correlation, etc.) in a high-dimensional feature space (e.g. the metagenomic space). The collection of all nonlinear pairwise distances forms a distance matrix called MC-distance matrix or MC-kernel, which can be used as an input in algorithms for dimensionality reduction, classification and generally in machine learning (Cannistraci et al, 2010). In MCE, the MC-kernel can be centred or non-centred, and its singular value decomposition is used to favour a sample projection onto a two-dimensional space for visualisation and analysis. Thus, MCE is a form of nonlinear and parameter-free kernel PCA.

Results: Does proton pump inhibitor (PPI) treatment significantly modify the gastric microbiota? In order to answer this question, we collected 24 gastric biopsy samples from subjects: 12 under PPI treatment, 4 untreated Helicobacter pylori positve (HP+), 4 untreated Helicobacter pylori negative (HP-) and 2 untreated undefined. Amplicons were sequenced on a Roche 454 plataform.

Using PCA (and other linear methods) we found that our samples do not appear to differentiate according to treatment. This could be a normal conclusion that researchers would draw by applying classical multivariate analysis on case-control metagenomic datasets, such as ours, in many labs across the world. However, we decided to test whether the presence of nonlinear relations between the samples would represent a cause for the linear multivariate approach to fail. In fact, our further analysis showed that MCE can clearly separate samples according to the different conditions and treatments in cases in which PCA fails to reveal any clear structure. We were also able to use MCE to perform reverse engineering of the discriminant bacterial 'social networks' responsible for the separation between the different conditions.

Conclusion: The juxtaposition of PCA and MCE visualisations can provide a novel standard of multivariate analysis for discovering and validating significant linear/nonlinear complementary patterns in metagenomic data and, in general, in case-control omic studies.

Disclosure of Interest: None declared

P0616 CHARACTERIZATION OF VESICLE-ENCLOSED AND MEMBRANE-BOUND RNA AND DNA CONTENT IN CANCER-DERIVED EXTRACELLULAR VESICLES

D. Santare¹, C. Bajo Santos²³, A. Abols², J. Stefanovics², E. Zandberga², A. Line²

¹Faculty of Medicine, University of Latvia, ²Latvian Biomedical Research and Study Centre, ³Faculty of Biology, University of Latvia, Riga, Latvia

Introduction: Extracellular vesicles (EVs) have recently emerged as mediators of intercellular communication both in normal physiological and pathological processes, including cancer. They have been shown to carry mRNAs, non-coding RNAs, proteins and even gDNA fragments harbouring specific mutations, therefore EVs in biological fluids may serve as a “liquid biopsy” of cancer. Nevertheless, controversy regarding nucleic acid (NA) location has arisen two possible scenarios: the first suggests that all NAs are selectively sorted inside EVs, while the second suggests that NAs are randomly attached to the surface of EVs.

Aims & Methods: The aim of the current study was to characterize the vesicle-enclosed and surface-bound RNA and gDNA content in EVs isolated from colorectal (SW480), breast (MDA-MB231) and lung (A549) cancer cell cultures and plasma samples from cancer patients and healthy controls (n=12). EVs were isolated using size-exclusion chromatography and characterized by electron microscopy and Western blot analysis using specific EV markers (CD9, CD81, CD63, Alix), H3 as a marker for apoptotic bodies and GM130 as a negative control. Then, EVs were treated with RNaseI or DNaseI followed by total NA extraction from the treated and non-treated samples. NA amount was measured by Qubit and 2100 Agilent Bioanalyzer and expression levels of 5S and 28S rRNAs and selected miRNAs were quantified by RT-qPCR.

Results: Treatment of EVs with RNAse showed that 30 to 60% of EV RNA content was attached to the surface of EVs obtained from various cell cultures. Further expression analysis revealed that rRNA fragments were predominantly located on the surface of EVs, while the majority of miRNAs were enclosed within the vesicles. The total amount of RNA tended to lower in plasma-derived EVs than in cell culture-derived EVs, yet the proportion of vesicle-enclosed and surface-bound RNA was 90% vs 10%. Regarding gDNA content, we found that DNA amount varies significantly among the cell lines and 20 to 40% of DNA fragments were attached to surface of cell line-derived EVs, while plasma EVs contained 50-fold lower amounts of gDNA than EVs derived from the cell lines.

Conclusion: This study showed that miRNAs are predominantly packed inside EVs derived from cancer cell lines and patients’ plasma, while rRNA and gDNA fragments are found in the vesicle-enclosed and surface-bound form. Furthermore, the NA yield tends to be lower in plasma-derived EVs than those produced by cancer cell lines suggesting that either cancer cells secrete EV-associated NAs more efficiently than normal cells or the enhanced NA secretion is an in vitro phenomenon. (Financed by project 625/2014)

Disclosure of Interest: None declared

P0617 VIABLE CYTOGENETIC BIOMARKERS FOR ADVANCED COLORECTAL NEOPLASIA IN AVERAGE RISK PATIENTS

E. M. Ionescu¹, T. Nicolaie¹, A. Ionescu¹, M. Diculescu², M. Ciocirlan²

¹Gastroenterology Department, Elias Emergency Hospital, Bucharest, Romania, ²Gastroenterology and Hepatology Clinic, Fundeni Clinical Institute, Bucharest, Romania, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania, Bucharest, Romania

Contact E-mail Address: mirela.ionescu80@gmail.com

Introduction: Loss of genetic stability seems to be one of the main pathogenic key processes appearing early in carcinogenesis of colorectal carcinomas (CRC). We used the Cytokinesis-Bloked Micronucleus Assay (CBMN) technique for detecting DNA damages. The aim of our study was to predict the presence of significant colorectal lesions by specific biomarkers detected by this method in average risk persons.

Aims & Methods: We designed a prospective study including patients undergoing diagnostic or opportunistic screening colonoscopy. A blood sample was obtained from each patient to to be analyzed by CBMN technique for specific biomarkers: presence of micronuclei (MN), nucleoplasmic bridges (NPB) and the Nuclear Division Index (NDI).

Results: 98 patients met the inclusion criteria, 57 of them assimilated to average-risk persons (age between 50-75 years, with no personal or familial CRC history). The mean age of our group was 55.36. The advanced neoplasia rate was 34.68% for the entire group. In the average-risk group 21.05% had advanced adenoma and 26.31% adenocarcinomas. MN frequeny and NPB presence were not significanty different in patients with neoplastic lesions compared to normal population or non-neoplastic colorectal lesions. NDI was significant lower in patients with adenoma or adenocarcinoma versus individuals with normal colonoscopy or non-neoplastic lesions, in the whole group but also in average-risk group (AUC ROC = 0.668, p = 0.005 and AUC ROC = 0.715, p = 0.006 respectively). For a cutt-off value of NDI =1.8, the sensitivity in detecting any neoplasia was 97.7% for all patients and 97% for medium-risk patients. NDI was significantly lower in patients with advanced neoplasia compared with individuals with normal colonoscopy or with non significant colorectal lesions (AUC ROC = 0.636, p = 0.029 for all patients, AUC ROC = 0.672, p = 0.029 for average-risk group). For the same cut-off value of NDI of 1.8, the sensitivity in detecting advanced neoplasia was 97% for all patients and 96% for average-risk group. When predicting only carcinomas, an NDI value of < 1.8 will predict it with a sensitivity of 94.4% for all patients and 93.3% for average-risk group.

Conclusion: We found a significantly low Nuclear Division Index in patients with advanced colorectal neoplasia in average risk individuals. NDI score may have a certain value in colorectal cancer screening.

Disclosure of Interest: None declared

P0618 VALIDATION OF SMARTPILL WIRELESS MOTILITY CAPSULE FOR GASTROINTESTINAL TRANSIT TIME

P. M. Hellström¹, H. D. Tartera¹, A. Al-Saffar¹, M. A. Halim¹, D.-L. Webb¹, G. Lindberg², P. Sangfelt¹

¹Medical Sciences, Uppsala University, Uppsala, ²Medicine, Karolinska Institutet, Stockholm, Sweden

Introduction: Normal values for gastrointestinal transit time were quantified in healthy Swedish volunteers using SmartPill^® wireless motility capsule (WMC). This ambulatory method, permits motility recordings (transit time and luminal pressure) in real time, by 5 days, without exposing to radiation, and it possible study the response to food intake, bowel movements, normal daily activity, periods of pain and discomfort. We wanted establish WMC normal values for gastric emptying, small bowel, colon and whole gut transit. Furthermore, evaluated the stability of recordings upon repeat recordings and estimated the fidelity of naked-eye inspection of transit values vs software-aided values; and finally comparison of gastric emptying and small bowel transit as measured by video capsule endoscopy (VCE) was made.

Aims & Methods: Seventy-two healthy volunteers ingested a 260 kcl meal, and SmartPill^® with 100 ml of water, after which food intake ad libitum was permitted. Data obtained from the WMC was transferred to a receiver carried; values presented were regional (gastric, small bowel, colon), and total transit time, and other group of 75 subject taked the under fasting conditions.

Results: Using the SmartPill in 72 healthy subjects we obtained the following normal values displaying a Gaussian distribution (hours): Gastric emptying time (GET) 2.87-3.38, Small bowel transit time (SBTT) 4.82-5.67, colon transit time (CTT) 18.50-23.27, and whole gut transit time (WGTT) 27.03-32.20. The variation coefficient varied between 33 to 48% indicating a certian spread of values. The maximum GET was 6.1, Max SBTT 11.2, max CTT 54.9 and max WGTT 68.1. Comparison between software and physician evaluation we obtained a correlation of r=0.99 for WGTT. The Bland-Altman plot analysis exhibited only one single outlier in repeated measurements after 1 and 2 weeks. The comparison of SmartPill and PillCam GET and SBTT regularly showed shorter transit times with PillCam, most likely as a result of the fasting condition with PillCam as compared with SmartPill (P < 0.05).

Conclusion: The SmartPill WMC gave robust data of transit times for passage through different regions of the gastrointestinal tract. Our results suggest that the SmartPill technology is able to detect transit times for passage through different regions of the gastrointestinal tract. Estimates of transit are reliable with little differences from physicians “true” estimates by visual readings. Furthermore, capsule endoscopy may not substitute for WMC for estimates of transit as done under other conditions and defined by anatomical landmarks rather than functional divides in the gut. The feasibility of the recordings as well as the useful interpretation softare makes the SmartPill a strong competitor for use in the clinical setting where its use is comparable to that of the PillCam. Swift and easy trustful values of gastric emptying, small bowel transit and colon transit values can be obtained in order to verify gastroparesis, constipation and possibly also high amplitude contractions causing painful discomfort in patients with enteric dysmotility.

Disclosure of Interest: None declared

P0619 METABOLITE PROFILING IN HUMAN COLORECTAL CANCER BY GAS CHROMATOGRAPHY / MASS SPECTROMETRY (GC/MS) REVEALS BACTERIAL METABOLITES AND CHANGES IN ENERGY METABOLISM

W. Erhart¹, W. von Schönfels², M. Brosch³, J.-H. Egberts², B. Schniewind⁴, C. Röcken⁵, T. Becker², S. Schreiber¹, C. Schafmayer², J. Hampe³

¹1. Medical Department, ²Department of General and Thoracic Surgery, Universitiy Hospital Schleswig-Holstein, Campus Kiel, Kiel, ³Department of Medicine I, University hospital Dresden, Dresden, ⁴Department of Surgery, Hospital Lüneburg, Lüneburg, ⁵Institute of Pathology, Universitiy Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

Contact E-mail Address: wiebke.erhart@uksh.de

Introduction: Colorectal cancer (CRC) is a common malignancy worldwide. Numerous parameters including genetic alterations, lifestyle factors as well as the composition of colonic microflora are relevant in CRC development. Tumour-specific metabolic changes progressively attract interest in the perpetuation of a malignant phenotype since they provide a chance to understand the tumour's biology.

Aims & Methods: We investigated paired samples of normal colon tissue and colorectal cancer tissue of 53 CRC patients. The samples were gained during endoscopy, thus, avoiding long ischemic time usually coming along with tumour surgery. Gas chromatography / mass spectrometry (GC/MS) was performed to analyse differences in metabolic profile of normal and tumourous tissue of CRC patients.

Results: Several differences in metabolic profile of normal and malignant transformed tissue were revealed. These included changes in energy household and cell turnover in tumorous tissue like dysregulation of tricarboxylic acid (TCA) cycle, increase of glycolysis, and augmented protein formation. Furthermore, several metabolites arising in microbial metabolism were found at heightened levels in cancer tissue.

Conclusion: In conclusion, GC/MS metabonomics revealed interesting differences in the metabolic profiling of human CRC and normal colon mucosae. Especially, the significant disparity in abundance of bacterial metabolites reflecting the importance of composition of colonic microflora in the development of CRC is worth further investigation. A better understanding of tumour´s biology has a great potential in the development of personalized therapeutic strategies in the treatment of this common neoplasia.

Disclosure of Interest: None declared

TUESDAY, OCTOBER 27, 2015   09:00-17:00

LIVER & BILIARY II – HALL 7__________

P0620 H63D/H63D GENOTYPE AND H63D ALLELE PREDISPOSE PATIENTS WITH HYPERFERRITINEMIA TO DEVELOP METABOLIC SYNDROME

A. Castiella¹, E. Zapata¹, M. D. De Juan², L. Zubiaurre¹, A. Iribarren¹, P. Otazua³, J. I. Emparanza⁴

¹Gastroenterology, Mendaro Hospital, mendaro, ²Immunology, Donostia Universitary hospital, Donostia, ³Gastroenterology, Mondragon Hospital, Mondragon, ⁴Clinical Epidemiology, Donostia Universitary hospital, Donostia, Spain

Contact E-mail Address: agustincastiella@yahoo.es

Introduction: Nearly 25% of adult population in western countries have the metabolic syndrome (MS). Hyperferritinemia (HF) is frequently present in patients with this clinical entity (dysmetabolic hyperferritinemia). The presence of mutations in the HFE gene, like the H63D/H63D mutation, may induce MS in these patients.

Aims & Methods: A Prospective study of 132 consecutive patients with HF (> 200μg / L women, > 300μg / L men) was conducted from January to December 2010. The Metabolic syndrome was defined by the presence of waist circumference ≥94cm men; ≥80 cm women. And two of the following factors: Triglycerids ≥ 150 mg/dL or treatment for this dislypemia; HDL <40 mg/dL women, <50 mg/dL men or treatment for this dislypemia; glucose ≥ 100 mg/dL or Type 2 diabetes; hypertension: blood pressure ≥130 mm Hg/ ≥85 mm Hg. or treatment for arterial hypertension. DNA was extracted from the blood samples and HFE gene analysis was performed by multiplex real-time PCR using LightCycler technology (LC 1.0). Simultaneous detection of the HFE C282Y, H63D and S65C mutations was carried out in a single capillary using LC-Red 640, LC-Red 705 and fluorescein-labelled hybridization probes (Tibmolbiol, Berlin, Germany). Melting curve analysis was used to distinguish wild type and mutant alleles in each case. The results were compared with a control group of blood donors from the same geographical area.

Results: In 97 from 132 patients we have all the data to determine the MS presence: 44/80 men (55%) and 10/17 women (59%) presented MS. The HFE mutations from 51/54 patients with MS were: 2 C282Y/wt (3.92%); 11 H63D/H63D (21.56%); 15 H63D/wt (29.41%); 3 C282Y/H63D (5.88%); 19 wt/wt (37.25%); 1 S65C/ wt (1.96%). The genotype frequency of the H63D/H63D mutation in MS cases was significantly higher than in controls (7) - 21.56% vs 7.76%> (p=0.011); the H63D allelic frecuency was 42.15% in MS group and 31% in controls (p=0.027).

Conclusion: The H63D/H63D genotype and H63D allele predispose individuals with HF to MS.

Disclosure of Interest: None declared

P0621 A1166C AGTR1 AND I/D ACE GENETIC POLYMORPHISMS DETERMINE REGULATION OF CHEMOKINES AND FORMATION OF THE VICIOUS CIRCLE INVOLVING ENDOTHELIAL DYSFUNCTION OF MESENTERIC VESSELS AND INTESTINAL DYSBIOSIS IN HEPATIC STEATOSIS

A. Sydorchuk¹, T. Boychuk¹, L. Sydorchuk¹, I. Sydorchuk¹, R. Sydorchuk¹

¹Bukovinian State Medical University, Chernivtsi, Ukraine

Contact E-mail Address: rsydorchuk@ukr.net

Introduction: Fatty liver disease or Hepatic Steatosis (HS) is frequently observed in patients with arterial hypertension (AH) as they both have common systemic pathogenesis realized through metabolic and immune mechanisms involving vascular and digestive system injury. Moreover, chronic vascular damage influences intestinal byocenosis causing further damage to liver. We hypothesized that the combination of vascular and metabolic changes may have detectable genetic background.

Aims & Methods: The aim is to evaluate the endothelial function and mesenteric vessels remodeling depending on I/D polymorphism of angiotensin-converting enzyme (ACE) gene and A1166C polymorphism of angiotensin II type 1 receptor (AGTR1) gene in patients with HS and AH.

Study included 104 patients with HS combined with AH (50 female, 54 male, age 53.2 ± 8.7). Intimae-media thickness (IMT) of abdominal aorta (AO) and other flow mediated parameters of mesenteric vessels status were evaluated by sonography. Nitric oxide (NO) and nitrite/nitrate plasma concentrations, vascular adhesive molecule (sVCAM-1) levels were defined by ELISA. ACE (I/D) and AGTR1 (A1166C) genes polymorphisms assessed with PCR.

Results: High risk of endothelial dysfunction is associated with D-allele of ACE gene (p<0.001) and C-allele of AGTR1 gene (p=0.02). Flow-mediated parameters of mesenteric vessels were higher in DD-genotype patients. IMT of abdominal aorta was higher in CC-genotype of AGTR1 gene (p=0.039-0.01) and no dependence was found on I/D genotypes of ACE gene. sVCAM-1 level was significantly higher in D-allele of ACE gene (p < 0.01) than in II-genotype and not depending on A1166C polymorphism of AGTR1 gene. Nitric oxide plasma level does not depend on ACE (I/D) and AGTR1 (A1166C) genes polymorphisms. Vascular remodeling in HS patients (AO IMT enlargement for more than 0.9 mm) is associated with III-IV grades intestinal dysbiosis and 1.3-1.6 times growth of sVCAM-1 plasma levels (p < 0.05-0.001). AO IMT strongly positively correlates with dysbiosis severity (r=0.69-0.83), presence of HS and sVCAM-1 level (r=0.64-0.87) and is not dependent on arterial hypertension severity.

Conclusion: Risk contingents for endothelial dysfunction and mesenteric vessels remodeling in HS patients include DD-genotype carriers of ACE gene because of increased sVCAM-1 plasma levels and diameter of mesenteric vessels; and CC-genotype carriers of AGTR1 gene due to significant enlargement of Intimae-media thickness of abdominal aorta (p ≤ 0.02-0.001).

Disclosure of Interest: None declared

P0622 NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) AS POTENTIAL RISK FACTOR OF CARDIOVASCULAR DISEASE AND ONCOLOGICAL DISEASE IN DIABETIC TYPE 2 PATIENTS

D. Caroli¹, A. Nogara², E. Rosa-Rizzotto¹, A. Boscolo Bariga², F. De Lazzari¹

¹Gastroenterology Unit, Padova, ²Internal Medicine, Chioggia, Italy

Introduction: NAFLD is an increasingly cause of liver damage in western countries associated with obesity, hypercaloric diet and the sedentary lifestyle. The increasingly high prevalence of NAFLD and its possible damage on several organs due to its inflammatory effects (cardiovascular risk and oncological risk) will lead to a prioritary health care problem in the next future. Validated prognostic scores for NAFLD and for cardiovascular risk in diabetics patients were respectively Fatty liver index (FLI) and UK Prospective Diabetes Study (UKPDS risk engine)

Aims & Methods: The aims of our study are to assess the real correlation between FLI and UKPDS risk with cardiovascular (CE) and oncological events (OE) in a cohort of diabetic type 2 patients, in order to identify with accurancy the best predictor. 2004 patients referred to our Diabetics Center Ambulatory and in a regular follow-up were retrospectively tested. UKPDS risk and FLI were calcolated for each patient. Data such as CE, OE, anthropometric, biochemical and metabolic features were also collected. T test for unpaired data and Pearson Chi-squared test were performed.

Results: 304/2004 pt (15%), 211 M and 93 F, were FLI >60; in this group we observed 14 (5%) OE (7 M and 7 F) and 81 (27%) CE (64 M and 17 F). 743/2004 pt (37%), 638 M and 17 F), were FLI < 20; in this other group we observed 9 (1%) OE (6 M and 3 F) and 74 (10%) CE (47 M and 27 F). The statistical analysis showed that patients with FLI > 60 have a higher risk of OE (p=0.0006) or CE (p=0.0001) compared to patients FLI < 20. We identified also two peculiar profiles of cardiovascular risk, in fact male gender patients with FLI > 60 presented a significant higher risk of developing CE than female (p < 0.05); instead female gender patients with FLI < 20 presented a significant higher risk of developing CE than male (p < 0.001). No statistical significance was found between FLI > 60 +UKPDS >20 and CE (p=0.754). FLI > 60 and FLI < 20 patients also significantly differed respectively for mean age 62.2 vs 68.4 y (p=0.02), duration of diabetes 4.9 y vs 13.24 y (p=0.002) and mean glycated hemoglobin 8.7y vs 7.9 (p=0.009).

Conclusion: An early and aggressive program of follow-up and treatment could be established in diabetic type 2 patients with FLI > 60 and so with reasonable suspicion of NAFLD because this population have higher risk to develop CE and OE in comparison to FLI < 20 (or FLI negative and not suspicion of NAFLD). The simultaneous UKPDS and FLI positivity doesen't improve accuracy in predicting CE.

Disclosure of Interest: None declared

P0623 HIGH BODY MASS INDEXES PRESERVE BONE MINERAL DENSITIES IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE

M. Farrugia¹, M. Gerada¹, J. Bonello¹, J. M. Gauci¹, R. Pullicino², J. Gerada¹

¹Gastroenterology, ²Radiology, Mater Dei Hospital, Msida, Malta

Contact E-mail Address: jurgen.gerada@gmail.com

Introduction: The effect of non-alcoholic fatty liver disease (NAFLD) on bone mineral density (BMD) is poorly understood. NAFLD is more prevalent with higher body mass indexes (BMI).

Aims & Methods

Aim: We aimed to evaluate the effect of different classes of BMI on BMD in adult patients with NAFLD.

Methods: Adult patients diagnosed with NAFLD on liver imaging in 2013 were enrolled in the study. Patients with concomitant liver pathologies were excluded. Patient demographics were obtained from the medical notes and the BMI was calculated and classified using the WHO classification (underweight (<18.5), normal (18.5-24.9), overweight (25-29.9) and obese (≥30)). BMDs of the femur and lumbar spine were measured in all patients by dual energy X-ray absorptiometry. Age and gender-matched Z scores and T scores were calculated and analysed against the different BMI classes using the ANOVA model.

Results: 197 NAFLD patients were enrolled in the study (178 females, 90.3%; mean age 63.5, range 35-82; mean BMI 32.8, range 22-48.6). No underweight patients were present in the study. Obese patients had higher BMD T scores (-0.38 ± 1.12) of the whole femur than overweight patients (-0.82 ± 1.074) and normal BMI patients (-1.53 ± 0.89) (p 0.001). This was also true for the femoral neck (-0.97 ± 1.14, -1.41 ± 1.00, -1.77 ± 0.95, respectively, p 0.007) and lumbar spine (-0.71 ± 1.38, -1.06 ± 1.16, -1.80 ± 1.62, respectively, p 0.017). Likewise, obese patients had higher BMD Z scores of the whole femur (0.71 ± 1.09, p 0.002), femoral neck (0.59 ± 1.1, p 0.005) and lumbar spine (0.46 ± 1.36, p 0.008) compared to overweight patients (0.26 ± 1.15, 0.16 ± 1.03, 0.04 ± 1.15 respectively) and normal BMI patients (-0.25 ± 0.79, -0.25 ± 0.84, -0.65 ± 1.31 respectively). On subgroup analysis of obese patients, obese class 3 patients (BMI >40) had higher BMD T scores of the whole femur (p 0.002) and lumbar spine (p 0.003) but not of the femoral neck (p 0.321) when compared to obese class 2 (BMI 35-39.9) and obese class 1 (BMI 30-34.9) patients.

Conclusion: In NAFLD patients, obesity was associated with stronger bone mineralisation, demonstrating a linear relationship with increasing BMIs. NAFLD patients with normal BMI should undergo BMD to screen for osteopenia. Weight loss in NAFLD obese patients might have deleterious effects on bone health.

Disclosure of Interest: None declared

P0624 URSODEOXYCHOLIC ACID INFLUENCE ON EFFICACY AND SAFETY OF STATIN THERAPY IN PATIENTS WITH HIGH RISK OF CARDIOVASCULAR EVENTS AND NONALCOHOLIC FATTY LIVER DISEASE: THE RACURS STUDY (POST-HOC ANALYSIS)

M. Nadinskaya¹, S. Martsevich², N. Kutishenko², I. Balashov², O. Lerman²

¹Department of Propaedeutics, I. M. Sechenov First Moscow State Medical University, ²Federal State Institution National Research Center for Preventive Medicine, Moscow, Russian Federation

Contact E-mail Address: marianad@rambler.ru

Introduction: The RAKURS study included 62% of patients with a history of nonalcoholic fatty liver disease (NAFLD).

Aims & Methods: To assess the ursodeoxycholic acid (UDCA) influence on efficacy of statin therapy in patients with high risk of cardiovascular events (CVE) and NAFLD.

Data of case report forms of 262 patients enrolled in the RAKURS study. NAFLD group – 234 subjects – is formed based on ultrasonic data (hyperechoic appearance of hepatic parenchyma) at the moment of enrollment. It was divided into two subgroups: fatty liver (159 subjects) – patients with normal level of ALT, and nonalcoholic steatohepatitis (NASH, 75 subjects) – patients with elevated level of ALT (the median is 58.9 U/l). The fatty liver subgroup included patients significantly older than in the NASH subgroup: mean age was 61.62 ± 8.19 and 57.86 ± 8.76 years, respectively (p < 0.05). The NASH included more men: 65% vs 42% in the fatty liver subgroup (p < 0.05).

Results: Statin therapy in combination with UDCA in the fatty liver subgroup was administrated to 92%, in the NASH subgroup – to 97% of patients. The subgroups did not show any difference in terms of initial total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG).

After 6 months of follow-up there was a significant (p < 0.05) reduction in TC to 4.1 mmol/l, LDL-C to 1.89 mmol/l and TG to 1.24 mmol/l in the fatty liver subgroup, and TC to 4.0 mmol/l, LDL-C to 1.9 mmol/l and TG to 1.3 mmol/l in the NASH subgroup. Changes of the above listed levels were similar in the subgroups. In the NASH subgroup there was a significant (p < 0.05) decrease in ALT to 30 U/l. The dynamics of alkaline phosphatase, gamma glutamine transferase, bilirubin and creatinphosphokinase remained within reference range during the whole period of the treatment.

Among the patients who were taken lipid-lowering therapy for the first time (47 subjects in the fatty liver subgroup and 24 subjects in the NASH subgroup), initial higher TC 6.47 mmol/l and TG 2.03 mmol/l were observed in the NASH subgroup vs TC 6.1 mmol/l and TG 1.19 mmol/l in the fatty liver subgroup. LDL-C was similar in the both subgroups: 3.9 mmol/l. At the end of the first month of statin therapy combined with UDCA in the fatty liver subgroup there was a decrease in TC to 5.1 mmol/l, LDL-C to 3.17 mmol/l, TG to 1.62 mmol/l; in the NASH subgroup there was a decrease in TC to 4.8 mmol/l, LDL-C to 2.72 mmol/l and TG to 1.62 mmol/l. The decrease of the above listed levels was more evident (p < 0.05) in the NASH subgroup. A significant positive dynamics of ALT decrease to 53.5 U/l was found in patients with NASH (initially 58.7 U/l).

Conclusion: 6-month statin therapy in combination with UDCA showed significant lipid-lowering effects in patients with high risk of CVE and NAFDL, as well as normalization of ALT in the NASH subgroup. Among the patients who previously had not taken statins in the NASH subgroup, higher levels of TC and TG were observed. The same subgroup showed more evident lipid-lowering effects than the fatty liver subgroup during the first month of the treatment.

Disclosure of Interest: None declared

P0625 METABOLOMIC MARKERS OF LIVER DAMAGE AND THEIR IMPLICATION IN THE ADVANCEMENT OF LIVER INJURY: FROM FATTY LIVER TO HEPATOCELLULAR CARCINOMA

M. Gaggini¹, C. Saponaro¹, C. Rosso², F. Carli¹, E. Buzzigoli¹, F. Filipponi³, D. Ciociaro¹, E. Bugianesi², A. Gastaldelli¹

¹Cardiometabolic Risk Unit, Institute of Clincal Physiology, Pisa, ²Dept. of Medical Sciences, Division of Gastroenterology and Hepatology, Turin, ³Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy

Contact E-mail Address: melania.gaggini@alice.it

Introduction: The liver is a key organ in general metabolism and waste handling. Non alcoholic fatty liver disease (NAFLD), can progress to steatohepatitis, fibrosis and cirrhosis, and also to hepatocellular carcinoma (HCC) independently from cirrhosis. Chronic liver disease is associated with alterations in hepatic and whole body lipid metabolism caused by lipotoxicity due to elevated free fatty acid (FFA), oxidative stress and IR. Together these events play a significant role in determining the progression of liver disease.

Aims & Methods: Since circulating metabolites have been proven to be excellent markers of liver function, the aim of this work was to evaluate plasma small-molecule that could mark NAFLD and their differences in subjects with different degrees of liver damage vs. those that already developed HCC.

In 44 patients with NAFLD evaluated with biopsy, 47 patients with HCC and 21 subjects without liver disease (CT), we evaluated, by gas chromatography mass spectrometry, FFAs composition, de novo lipogenesis index (DNL= palmitic/linoleic acid), unsaturated to saturated fat ratio (PUFA/SFA), and a new index (GSG index) of liver damage calculated as glutamate/(serine+ glycine). Moreover we evaluated Adipose tissue (Adipo-IR= FFA x Insulin) and peripheral (HOMA = glucose x Insulin/22.5) insulin resistance. Histology was scored according to Kleiner. APRI score (AST/platelet count), that is an index of fibrosis, was calculated in all subjects.

Results: Patients with liver disease had increased IR, especially in HCC that showed higher Adipo-IR (16.4 ± 1.7 vs 8.4 ± 0.8 vs 5.6 ± 0.9) and HOMA (8.38 ± 0.76 vs 3.21 ± 0.28 vs 2.04 ± 0.32) compared to NAFLD and CT (all p < 0.005). The worsening of liver disease was associated with the increase of DNL index and a decrease in PUFA/SFA ratio that was more evident in HCC than NAFLD compared to CT (p < 0.0001). In NAFLD, DNL index and PUFA/SFA changed proportionally to the severity of fibrosis particularly with Fibrosis score 3-4 (all p < 0.0001). GSG-index was increased proportionally to liver enzymes, (all p < 0.0001) and was higher in patients with Fibrosis score 3-4 or HCC compared to CT or no fibrosis. In all subjects, GSG, DNL and PUFA/SFA were related to Adipo-IR (R=0.23;R=0.34;R=-0.38) and HOMA (R=0.25;R=0.43;R=-0.20). Moreover, we found that the increase in APRI score in subjects with FLD and HCC was associated with adipose tissue IR and HOMA DNL index, GSG index and the PUFA/SFA ratio (all p < 0.0001).

Conclusion: We found several metabolomic markers of liver damage (GSG, DNL, PUFA/SFA, adipo-IR, HOMA) that mark differences in degree of liver fibrosis in NAFLD or presence of HCC, indicating metabolic dysfunction as one of the major risk factors for liver disease.

Funding from the FP7/2007-2013 under grant agreement n°Health-F2-2009- 241762, for the FLIP project, CNR-Interomics

Disclosure of Interest: None declared

P0626 PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA PRO12ALA GENE POLYMORPHISM DETERMINES PERSONALIZED THERAPY FOR FATTY LIVER DISEASE

O. Plehutsa¹, L. Sydorchuk², I. Sydorchuk², R. Sydorchuk²

¹District Hospital, Briceni, Moldova, Republic of, ²Bukovinian State Medical University, Chernivtsi, Ukraine

Contact E-mail Address: supers_stars@uni.de

Introduction: Multiple studies showed that Peroxisome Proliferator Activated Receptor gamma – NR1C3 (PPARG) plays an important role in various biological processes including lipid and glucose metabolism. PPARG has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis, and cancer. PPARG agonists have been used in treatment of different metabolic disorders and Nonalcoholic Steatohepatitis (NASH) norm regulating glucose metabolism, decreasing steatosis, inflammation, and fibrosis. However, existing data is confusing, challenging efficacy of therapeutic use of PPARG agonists.

Aims & Methods: The aim of the study was to clarify the perspectives for individualized therapy with thiazolidinediones depending on PPARG Pro12Ala polymorphism. 249 patients with metabolic syndrome, hypertension, and dyslipidemia participated in the study. Among them 50 (20.08%) patients with NASH were selected to form study group. PPARG agonist Pioglitazone administered 30 mg daily during 50-51 weeks. Genetic polymorphism (Pro12, Pro12Ala, Ala12Ala) of PPARG gene determined by PCR. Genotypes distributions were as follows: Pro12 Pro (n=32, 64.0%); Pro12Ala (n=14, 28.0%); Ala12Ala (n=4, 8.0%). Clinical examination and liver biopsies performed prior and after study.

Results: Pioglitazone improved glycemic control and glucose tolerance (P < 0.001), normalized liver aminotransferase levels as it decreased AST by 42.1 ± 1.17% P=0.014; ALT by 57.5 ± 1.37%, P < 0.001; decreased hepatic fat by 54.6 ± 2.09%, P < 0.001; and increased hepatic insulin sensitivity by 48.5 ± 1.63% P=0.006. Administration of pioglitazone caused improvement in histologic findings with regard to steatosis, ballooning necrosis, and inflammation. In 4 (8%) Ala12Ala patients no reliable changes were observed, except glycemic control and glucose tolerance. Reduction in fibrosis did not change significantly. Statistically insignificant weight gain and mild lower-extremity edema developed in two subjects with Pro12Ala genotype, no other side effects were observed.

Conclusion: Administration of thiazolidinediones leads to metabolic and histologic improvement in most patients with NASH. However, individual response may be affected by Pro12Ala polymorphism of PPARG gene. This study shows that carriers of Ala genotype whilst comparatively rare among NASH patients are much less sensitive to PPARG agonists' therapy. Our data partially explain the nature of failure of several thiazolidinediones use and their risk of side effects (bladder cancer or hepatitis).

Disclosure of Interest: None declared

P0627 HEPATIC GRANULOMAS: THE EXPERIENCE OF A TERTIARY CENTRE

R. M. Gaspar¹, P. Andrade¹, M. Silva¹, A. Peixoto¹, J. Lopes², F. Carneiro², G. Macedo¹

¹Gastroenterology, ²Centro Hospitalar São João, Porto, Portugal

Contact E-mail Address: ruilopesgaspar@gmail.com

Introduction: Hepatic granulomas have been reported in 2-15% of unselected liver biopsies.

Aims & Methods: The aim of our study was to evaluate the prevalence and the aetiology of granulomas in patients who underwent liver biopsy.

A retrospective review of hepatic biopsies performed in our Department between 2010 and 2015. Medical records, biochemistry tests as well as imaging and molecular studies that were relevant for the diagnosis were also reviewed.

Results: Over the study period, 1629 liver biopsies were performed. Hepatic granulomas were identified in 86 (5.3%). Of those, NASH accounted for the majority of cases (26.7%), followed by primary biliary cirrhosis (PBC) (17.4%), autoimmune hepatitis (AIH) (14%) and sarcoidosis (5.8%).

Infectious causes were less common, representing 16.5% of all cases: 4 cases of Hepatits C virus (HCV) infection, 1 case of Hepatits B virus (HBV) infection, 1 case of HBV/HCV coinfection, 1 case of Schistosomiasis, 1 case of Enterobiasis, 2 cases of Tuberculosis, 1 case of Q fever, 1 case of hepatosplenic candidiasis and 1 case of parasitic infection with no agent identified.

Two cases of drug toxicity were found, which were associated with antiretrovirals and etanercept use. Finally, 7 idiopathic cases were also reported.

Conclusion: In accordance with what has been described in previous studies, the prevalence of hepatic granulomas was 5.3%. Our study showed that NASH was the most common cause of granuloma formation, followed by PBC and AIH.

Differently to what has been reported in developing countries, infectious causes represented a small fraction of hepatic granulomas in our series.

Disclosure of Interest: None declared

P0628 PREVALENCE AND ETIOLOGY OF ELEVATED AMINOTRANSFERASES IN PORTUGAL

S. Carvalhana¹², J. Leitão³, A. C. Alves⁴, A. P. Silva⁵, F. Velasco⁶, I. Medeiros⁷, A. Carvalho³, M. Bourbon⁴, H. Cortez-Pinto¹²

¹Gastroenterology, Hospital de Santa Maria, ²Laboratorio Nutrição e Metabolismo, FML, Lisbon, ³Internal medicine, CHUC, Coimbra, ⁴INSA, Lisbon, ⁵Gastroenterology, CHVNG, Vila Nova de Gaia, ⁶CHA, Faro, ⁷Gastroenterology, HES, Évora, Portugal

Contact E-mail Address: sofiacarvalhana@msn.com

Introduction: Serum aminotransferases are often used in screening for liver disease. However, the prevalence and causes of elevated aminotransferases have geographic variations and there are no population-based data in Portugal.

Aims & Methods

Aims: determine the prevalence and factors associated with elevated aminotransferases in the general Portuguese population.

Methods: We conducted a nationwide, population-based cross-sectional study of adults resident in mainland Portugal. Serum biochemical liver tests (AST, ALT, GGT), serological markers for hepatitis B and C, as well as metabolic risk factors and alcohol consumption were assessed. Elevated aminotransferases (AST and/or ALT) was defined in women as ≥30 IU/L and in men ≥40 IU/L. The diagnostic criteria of NAFLD included hepatic steatosis (fatty liver index (FLI) >60), without excessive alcohol consumption (<20g/day).

Results: From 1688 individuals studied, 50.4% were men, mean age 50.2 ± 18.3 years and mean BMI was 27.0 ± 4.9 Kg/m², with 40.4% overweight and 22.8% obese. Insulin resistance (HOMA-IR>=3), hepatic steatosis (FLI > 60) and metabolic syndrome (MS) were 27%, 14% and 19%, respectively.

Prevalence of elevated aminotransferases was 10.7% (95% CI: 10.0-11.4). The probable cause of this elevation was NAFLD in 45%, excessive alcohol consumption (>20g/day) in 9.3%, HCV in 1.7%, HBV in 0.6% and unexplained cause in 43.4%.

Patients with elevated aminotransferases were mainly men (70%), overweight/obese (81%), with insulin resistance (47%), hepatic steatosis (42.6%) and MS (38.5 %), p < 0.05.

There was a significant positive correlation between aminotransferases and the following variables: FLI (r=0.29), NAFLD (r=0.18), BMI (r=0.17), HOMA-IR (r=0.14), gender (r=0.13), and MS (r=0.12). In multivariate analysis only FLI and BMI were independent risk factors for elevated aminotransferases. No correlation was found among aminotransferases and age, smoking and physical activity.

Conclusion: The prevalence of elevated aminotransferases was 10.7%. Fatty liver and the metabolic risk factors, namely MS and obesity, were the most frequent cause of their increase. These results emphasize the need for considering metabolic risk factors in the presence of elevated aminotransferases.

Disclosure of Interest: None declared

P0629 THE APPLICATION OF FATTY LIVER INDEX AND LIPID ACCUMULATION PRODUCT TO PREDICT METABOLIC SYNDROME IN SUBJECTS WITHOUT FATTY LIVER

W.-Y. Hsieh¹, C.-W. Su¹², Y.-C. Wang²³, M.-C. Hou²⁴, H.-C. Lin¹²

¹Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, ²Faculty of Medicine, School of Medicine, National Yang-Ming University, ³Healthcare Center, ⁴Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei City, Taiwan, Province of China

Contact E-mail Address: weiyaohsieh@gmail.com

Introduction: Fatty liver has shown strong association with metabolic syndrome in previous cross-sectional studies. Fatty liver index (FLI) is an algorithm to identify fatty liver while lipid accumulation product (LAP) which represents cardiometabolic disorders is used to predict liver steatosis as well. However their predicative value of metabolic syndrome in subjects without fatty liver is still obscure.

Aims & Methods

Aims: To explore the association between LAP and FLI, and metabolic syndrome in subjects without fatty liver.

Method: We enrolled consecutive subjects who received health check-up services at the Taipei Veterans General Hospital from 2002 to 2009. Ultrasonography was applied to diagnose fatty liver. The ability of the FLI and LAP to predict metabolic syndrome was assessed by analyzing the area under the receiver operating characteristic (AUROC) curve.

Results: Among the 29,797 subjects enrolled in this study, fatty liver was diagnosed in 44.5% of the population and it had the highest association with metabolic syndrome by multivariate analysis with an odds ratio of 2.499 (95% confidence interval 2.339-2.670, p< 0.001). Moreover, LAP and FLI are better than other serum markers to predict metabolic syndrome (AUROC: 0.884 and 0.875, respectively). Among the 16542 subjects without fatty liver, male gender, larger body mass index, older in age, higher serum alanine aminotransferase, and higher gamma-glutamyl transferase levels were correlated with metabolic syndrome by multivariate analysis. LAP and FLI are still better than other serum markers to predict metabolic syndrome in subjects without fatty liver (AUROC: 0.871 and 0.879, respectively).

Conclusion: FLI and LAP could accurately predict metabolic syndrome among subjects without fatty liver disease in a large-scale population in Taiwan. Accordingly, non-fatty liver patients with a high FLI or LAP may need intensified lifestyle modification and counseling.

Disclosure of Interest: None declared

P0630 PROGNOSTIC SIGNIFICANCE OF SYSTEMIC INFLAMMATORY AND IMMUNE BALANCE IN ALCOHOLIC LIVER DISEASE WITH A FOCUS ON GENDER-RELATED DIFFERENCES

B. Kasztelan-Szczerbińska¹, K. Celiński¹, A. Surdacka², J. Roliński², S. Miącz³, M. Szczerbiński¹, H. Cichoż-Lach¹

¹Dept. of Gastroenterology with Endoscopy Unit, ²Department of Clinical Immunology, Medical University of Lublin, Poland, ³Deptartment of Gastroenterology, Provincial Specialist Hospital in Lublin, Lublin, Poland

Contact E-mail Address: beata.szczerbinska@op.pl

Introduction: Mechanisms of inflammation in alcoholic liver disease (ALD) are still unclear. Th17 and regulatory T (Treg) cells are critically linked to inflammatory immune response. While Th17 lymphocytes exert pro-inflammatory effects, Treg cells are potent immune suppressors, and they may reciprocally control their function. Human Th17 differentiation is IL-1beta1, IL-6, IL-23 and IL-17A- dependent and suppressed by TGF-beta1. On the other hand TGF-beta1 enhances the differentiation of human Treg cells. To date, the Th17/Treg balance has not been explored in patients with ALD yet. Moreover, women develop more severe alcohol-associated liver injury at lesser ethanol intake and fewer years of exposure. They seem to respond stronger in comparison to males after inflammatory induction. It may result from different hormone patterns (estrogens are immune stimulators, testosterone is rather immunosuppressive).

Aims & Methods: The aim of our study was to determine an impact of the Th17 / regulatory T (Treg) cells balance and its corresponding cytokine profile on the ALD outcome. Possible gender-related differences in the alcohol-induced inflammatory response were also assessed. 147 patients with ALD were prospectively recruited, assigned to subgroups based on their gender, severity of liver dysfunction and presence of ALD complications at admission, and followed for 90 days. Peripheral blood frequencies of Th17 and Treg cells together with IL-1beta, IL-6, IL-17A, IL-23, and TGF-beta1 levels were investigated.

Flow cytometry was used to identify T cell phenotype and immunoenzymatic ELISAs for the corresponding cytokine concentration assessments. Multivariable logistic regression was applied in order to select independent predictors of advanced liver dysfunction and the disease complications.

Results: IL-17A, IL-1beta, IL-6 levels were significantly increased, while TGF-beta1 decreased in ALD patients. The imbalance with significantly higher Th17 and lower Treg frequencies was observed in non-survivors. IL-6 and TGF-beta1 levels differed in relation to the patient gender in ALD group. Concentrations of IL-6 were associated with the severity of liver dysfunction, development of ALD complications, and turned out to be the only independent immune predictor of 90-day survival in the study cohort.

Conclusion: IL-6 revealed the highest diagnostic and prognostic potential among studied immune biomarkers and was related to the fatal ALD course. Gender-related differences in immune regulation might influence the susceptibility to alcohol-associated liver injury.

Disclosure of Interest: None declared

P0631 A RETROSPECTIVE STUDY COMPARING SURVIVAL, RECIDIVISM AND COMPLICATIONS AFTER LIVER TRANSPLANTATION IN PATIENTS WITH ALCOHOLIC AND HCV-RELATED CIRRHOSIS

G. Vassallo¹, A. Mirijello², C. Tarli¹, M. Antonelli¹, F. Bernardini¹, L. Sestito¹, A. Gasbarrini¹, G. Addolorato¹

¹Institute of Internal Medicine, Catholic University of Rome, Rome, ²IRCSS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

Contact E-mail Address: g.addolorato@rm.unicatt.it

Introduction: Alcohol represents the most common cause of liver cirrhosis in the Western countries. Total alcohol abstinence represents the cornerstone in the management of alcoholic cirrhosis (AC). When liver function fails to improve with abstinence, liver transplantation (LT) is the treatment of choice. However LT in patients with AC remains controversial for the risk of alcohol recidivism after LT, and the perception of AC as a “self-inflicted disease”. Actually, HCV-related cirrhosis is the leading indication for LT.

Aims & Methods: The aim of this study was to evaluate the differences in terms of survival, recidivism and complications between patients who underwent LT for AC and HCV-related cirrhosis. A total of 297 patients who underwent LT at the Gemelli Hospital were retrospectively evaluated. In particular 66 (22.2%) patients underwent LT for alcoholic cirrhosis, and 52 (17.5%) patients for HCV-related cirrhosis. The survival rate was evaluated according to the Kaplan-Meier model. Recidivism for patients with AC was defined as any alcohol intake after LT. Recidivism for HCV-related cirrhosis was defined as histological evidence of chronic hepatitis C within 3 years of LT. Moreover post-surgery complications, chronic and acute rejection, onset of cancer, infectious, cardiovascular and metabolic disease was evaluated.

Results: Patients who underwent LT for AC showed a higher, however not significant, rate of survival than patients who underwent LT for HCV-related cirrhosis. Patients with HCV-related cirrhosis showed a significant higher prevalence of recidivism after LT (p=0.02). Patients transplanted for AC presented a significantly higher prevalence of cancer, in particular of upper digestive tract (p=0.04). No differences were found in the prevalence of cardiovascular, metabolic and infectious disease, rejection, and post-surgery complications between the two groups.

Conclusion: This study shows that our patients who underwent LT for AC have a higher survival rate and a lower recidivism rate than patients who underwent LT for HCV-related cirrhosis. No differences in terms of complications after LT were found between two groups, with the except of the higher prevalence of cancer in the AC group. These data are in line with previous literature data

Disclosure of Interest: None declared

P0632 ONE YEAR EFFECTIVENESS OF BACLOFEN TREATMENT IN 100 ALCOHOL-DEPENDENT PATIENTS

H. Lison¹, C. Barrault², A. Garioud¹, F. Roudot-Thoraval³, V. Behar², M. Medmoun¹, I. Rosa-Hezode⁴, C. Fourny², G. Pulwermacher⁵, H. Hagege⁴, J.-F. Cadranel¹

¹Hepatology Unit, Groupe Hospitalier Public du Sud de l’Oise, Creil, ²Addiction and Hepatology Unit, Centre Hospitalier Intercommunal de Créteil, ³Public health unit, CHU Henri Mondor, APHP, ⁴Hepatology Unit, Centre Hospitalier Intercommunal de Créteil, Créteil, ⁵Addiction and hepatology Unit, Groupe Hospitalier Public du Sud de l’Oise, Creil, France

Contact E-mail Address: armand.garioud@ghpso.fr

Introduction: Several studies have suggested efficacy of Baclofen (BAC) at low or high dose in reducing alcohol consumption. Since March 2014, Temporary Recommendation for Use of BAC has been allowed by the French drug agency (ANSM) in this indication.

Aims & Methods: The aim of the study was to assess effectiveness and safety of BAC at 12 months in alcohol-dependent patients with or without liver cirrhosis.

Between June 2010 and September 2013, 100 consecutive patients from 2 liver and alcohology units were included in this prospective open label study. Patients provided written consent before treatment initiation. BAC was orally administered at a dose of 15mg/day and weekly increased until alcohol indifference was obtained. The treatment was associated to social-psychological support and medical care.

Results: BAC was started in 100 patients (75 males, mean age 53 ± 9 years): 65 were cirrhotic and 16 had a chronic pancreatitis. After 1 year, 86 patients were still involved in the follow up, 83 were treated with BAC, 9 were lost of follow-up, 4 were dead and 1 had been transplanted. At a mean BAC dosage of 40mg/day [30–210], mean daily alcohol consumption (DAC) was reduced from 106 to 18g/day (p < 0.001). A decrease of the DAC > 50% was observed in 77 patients. Among them, a « low consumption » group of 64 patients was identified: 44 were completely abstinent and 20 drunk less than 30g/day. No predictive factor of response was identified. In this group, a significant improvement of consumption biomarkers was observed: decrease of mean gGT activity from 4.8N to 2N (p < 0.001), mean ASAT activity from 2.6N to 1.1N (p < 0.001) and mean erythrocyte globular volume from 100.6 to 92.8m3 and increase of mean platelets count from 171,000 to 193,000/mm3 (p=0.032). In the 39 cirrhotic patients of the « low consumption » group, total bilirubin serum concentration significantly decreased from 34.2 to 19.5mmol/L (p=0.026), prothrombin time increased from 69 to 77% (p < 0.001) and albuminemia increased from 34.2 to 37.2g/L (p=0.07). Twenty patients (20%) reported minor side effects leading to a treatment withdrawal in 2 cases. No liver or renal function deterioration occurred in cirrhotic patients.

Conclusion: In our cohort, baclofen treatment associated to a global care led to a dramatic reduction of alcohol consumption. This effective treatment is well tolerated and associated with a significant improvement of consumption biomarkers and of liver function tests in cirrhotic patients.

Disclosure of Interest: None declared

P0633 ABLATION OF THE SYMPATHETIC NERVOUS SYSTEM ATTENUATES CARBON TETRACHLORIDE-INDUCED OXIDATIVE STRESS IN LIVER: KEY ROLES FOR ALPHA-ADRENERGIC SIGNALING, HEPATIC INFLAMMATORY RESPONSE, AND HEME OXYGENASE-1 EXPRESSION

J.-C. Lin¹², S.-Y. Wang³⁴, Y.-J. Peng²⁴, M.-J. Lai⁴, T.-H. Young⁵, H.-S. Lee²³

¹Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, ²Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, ³Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, ⁴Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, ⁵Division of Gastroenterology, Department of Internal Medicine, Cardinal Tien Hospital, Fu Jen Catholic University, New Taipei City, Taiwan, Province of China

Contact E-mail Address: doc10506@gmail.com

Introduction: In addition to being the primary organ involved in redox cycling, the liver is also one of the most highly innervated tissues in mammals [1]. Although the sympathetic nervous system (SNS) is known to modulate both liver regeneration [2] and hepatic fibrosis [3], less is known regarding the role of the SNS in modulating the hepatic response to oxidative stress.

Aims & Methods: Our aim was to investigate the role of the SNS in healthy and oxidatively stressed liver parenchyma, theorizing that sympathectomized animals would be protected against oxidative stress. C57Bl/6JNarl male mice were treated with 6-hydroxydopamine hydrobromide to cause chemical sympathectomy or with either the α-adrenergic antagonist phentolamine or the β-adrenergic antagonist nadolol. Thereafter, carbon tetrachloride (CCl₄) injection was used to induce acute oxidative liver injury. Development of liver injury, oxidative stress, hepatocyte ultra-structural damage, and inflammatory responses were investigated.

Results: Sympathectomized animals were protected from acute CCl₄-induced liver injury as measured by an increase in lipid peroxidation as assessed by 4-hydroxy-2-nonenal (4-HNE) levels; elevation of serum alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) levels; DNA oxidative damage; and morphological features of cell damage. In addition, chemical sympathectomy modulated the CCl₄-induced inflammatory response within the liver. Attenuated injury in sympathecomized mice was associated with raised heme oxygenase-1 expression. CCl₄-induced lipid peroxidation and hepatotoxicity were suppressed by administration of an α-adrenergic antagonist.

Abstract number: P0633 Table.

Hepatic Lipid Peroxidation and Liver Function Tests in Mice after 24 Hours of CCl₄ Treatment.

Parameter	Saline + Olive oil	6-OHDA + Olive oil	Saline + CCl4	6-OHDA + CCl4	Phentolamine + CCl4	Nadolol + CCl4
4-HNE (μg/μg protein)	0.23 ± 0.02	0.18 ± 0.02**	0.33 ± 0.07*	0.23 ± 0.03##, ††	0.25 ± 0.01#	0.28 ± 0.02
ALT (IU/L)	40 ± 11	51 ± 28	15,519 ± 4,678***	7,809 ± 2,527##	7,318 ± 3,799#	10,830 ± 4,381

The results are presented as mean ± S.D.; * and ** Denote significant differences compared with the Saline + Olive oil group (p < 0.05 and 0.01, respectively); ^# and ^## Denote significant differences compared with the Saline + CCl₄group (p < 0.05 and 0.01, respectively)

Conclusion: We conclude that the SNS provides a permissive microenvironment for hepatic oxidative stress and injury indicating the possibility that targeting the hepatic α-adrenergic signaling could be a viable strategy for improving outcomes in patients with acute hepatic injury.

Disclosure of Interest: None declared

P0634 MECHANISTIC INSIGHT INTO CHLORPROMAZINE-INDUCED HEPATIC TIGHT JUNCTION DISRUPTION USING A HUMAN HEPARG-BASED LIVERBIOCHIP IMPEDANCE BIOSENSOR

A. Kozlowska¹, W. Gamal², K. Morgan¹, P. Treskes¹, P. C. Hayes¹, J. N. Plevris¹, P. O. Bagnaninchi², L. J. Nelson¹

¹Hepatology, ²Centre for Biomedical Engineering, University of Edinburgh, Edinburgh, United Kingdom

Contact E-mail Address: l.nelson@ed.ac.uk

Introduction: Chlorpromazine (CPZ) is an antipsychotic that can cause severe liver injury including intrahepatic cholestasis (jaundice). Preclinical in vitro models such as rat hepatocyte couplets or primary rat and human hepatocytes sandwich cultures have been the used to analyze hepatic transport processes. Dysregulation of the hepatobiliary transporter, bile salt export pump, is now recognized as a molecular initiating event in cholestasis. However existing models, including animal models, do not accurately predict cholestasis in humans. Therefore, new methods of detecting cholestatic liver injury caused by candidate compounds under development is critical. Cholestatics can also have profound effects on tissue architecture. For example, CPZ and cyclosporine-A have recently been shown to destabilize intercellular tight junctions (TJs) via oxidative stress-mediated effects on TJ-associated cytoskeletal pericanalicular F-actin distribution in a 2D human hepatic HepaRG cell model^1-2. HepaRG cells correctly localize hepatobiliary transporters to canalicular structures, comparable with primary human hepatocytes, and exhibit functional polarity³.

Aims & Methods: We aimed to develop a HepaRG-based LiverBioChip, as a preclinical test system for CPZ-mediated cholestatic liver injury, using impedance-based biosensing. Differentiated HepaRGs were cultured to confluence on 8-well (8W10E+) gold micro-electrode arrays. On day 8, CPZ time-/dose-response [0-100 μM] was monitored with quantitative impedance, |Z|, measurements (180s intervals; multiple frequencies: 4-64kHz) for 24h; to detect the TJ parameter (Rb), using |Z|-spectra modeling. Correlative hepatotoxicity/ phenotypic assays were performed: i) ATP-depletion; Prestoblue (PB: live-cell viability); and i) F-actin/phalloidin fluorescent staining.

Results: Real-time |Z| monitoring showed highly-sensitive/ temporal dose-response to CPZ; with a decrease of impedance at all frequencies, indicating a global decline in cellular health. Subsequent |Z|-spectra modelling reflected significant early (1h) disruption of TJ, and the cell-substrate adhesion parameter (z-alpha), at all CPZ doses [25, 50, 100 μM]. Endpoint ATP-depletion and PB assays (24h) correlated with |Z| changes only at the lethal [100 μM] dose. Fluorescent F-actin/phalloidin staining confirmed disruption to bile canalicular- [50-100 μM CPZ] and TJ-associated hepatic structures (ZO-1 TJ protein).

Conclusion: LiverBioChip provides a continuous/ quantitative real-time indicator of hepatic TJ integrity; revealing early, dose-dependent disruption of TJs even at sub-toxic CPZ levels (25 μM). This non-invasive platform may provide mechanistic insight into effects of putative cholestatic compounds for pre-clinical drug discovery.

Disclosure of Interest: None declared

P0635 DOPAMINE TRANSPORTER AVAILABILITY IN ALCOHOL-DEPENDENT PATIENTS BEFORE AND AFTER DEEP REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION: A 123I-FP-CIT STUDY

M. Antonelli¹, A. Ferrulli², G. Vassallo¹, A. Mirijello³, C. Tarli¹, F. Bernardini¹, L. Sestito¹, A. Gasbarrini¹, G. Addolorato¹

¹Institute of Internal Medicine, Catholic University of Rome, Rome, ²IRCCS Policlinico San Donato, San Donato Milanese, ³IRCSS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

Contact E-mail Address: g.addolorato@rm.unicatt.it

Introduction: Experimental and neuroimaging studies suggest a striatal dopaminergic dysfunction in alcohol dependence. Repetitive transcranial magnetic stimulation (rTMS) is a new promising treatment for substance addiction. Preliminary data in alcohol-dependent patients showed that rTMS of the dorsolateral prefrontal cortex increases dopamine release in the striatum, reducing craving.

Aims & Methods: The aim of this study is to assess DAT availability in actively drinking alcoholics before and after deep rTMS by 123I-FP-CIT SPECT, exploring changes in DAT levels and clinical parameters. We enrolled 14 untreated patients (12 M, mean age: 49 ± 10 years) with a DSM-IV diagnosis of alcohol dependence and a current alcohol drinking phase and without a major psychiatric disorder. After baseline SPECT scan, 11/14 patients were randomised to a real rTMS (n=5) or a sham stimulation (n=6). Each patient underwent 12 rTMS sessions for one month and a second SPECT scan was carried out at the end of treatment. Severity of alcohol dependence and craving were assessed before and after rTMS through the Alcohol Dependence Scale, Penn Alcohol Craving Scale and Obsessive Compulsive Drinking Scale. Anxiety and depression were evaluated by the State-Trait Anxiety Inventory and Zung Depression Self-Rating Scale. The alcohol Timeline Follow-back (TLFB) was used to estimate daily drinking. A ¹²³I-FP-CIT template was created with images of 20 healthy subjects (HS, 12 M, mean age: 47 ± 16 years). Patient scans were spatially normalised to the ¹²³I-FP-CIT template by SPM8. Analysis was performed using VOIs selected from a digital atlas; VOI mean activity concentration was obtained through Marsbar toolbox and Specific Binding Ratios (SBR) were calculated in the caudate nuclei and putamina.

Results: At baseline, alcoholics showed higher SBR in caudate nuclei and putamina (p < 0.05) in comparison with HS. An inverse correlation was found between SBR in the left caudate and anxiety levels (p < 0.05). After treatment, patients submitted to real rTMS had a reduction in SBR and no differences were any longer detected in comparison with HS. Conversely, patients submitted to sham stimulation showed higher SBR as compared with HS (p < 0.05) also at SPECT examination after treatment. When considering TLFB data, a significant reduction in alcohol intake (p < 0.05) was detected only in patients submitted to real rTMS.

Conclusion: Our preliminary data show that striatal DAT availability is increased in alcohol-dependent patients, supporting the assumption of a dysfunctional dopaminergic system. The finding of a SBR “normalization” as well as a reduction in alcohol intake after real rTMS, although obtained in a small sample, could suggest a clinical usefulness of deep rTMS.

Disclosure of Interest: None declared

P0636 INCIDENCE OF DRUG INDUCED LIVER INJURY AMONG GOVERNMENT TERTIARY HOSPITAL PATIENTS ON ANTI-KOCH’S TREATMENT

M. A. Malbog¹, M. Naval¹, F. Domingo¹, M. Chu¹

¹Section of Gastroenterology, Department of Internal Medicine, East Avenue Medical Center, Quezon City, Philippines, Quezon City, Philippines

Contact E-mail Address: milben473@yahoo.com

Introduction: Tuberculosis (TB) remains a major global health problem. Anti-TB drugs have proven efficacy against TB, however, they can induce various adverse events of which hepatoxicity is the most serious. Anti-tuberculosis drug induced liver injury (ATLI) is emerging as a significant threat to TB control, though limited data is available at present. This study aims to estimate the incidence of ATLI and understand its clinical features.

Aims & Methods: This was a single-center, prospective study which consisted of cohort of TB patients who received DOTS treatment at EAMC from December 2013 to May 2014. Only 285 patients who were at least 18 years of age were included. Clinical and laboratory features of ATLI were monitored for the treatment duration.

Results: We monitored 240 TB patients, 52 were dropped from the study while 188 continued. Nine patients developed ATLI with cumulative incidence of 4.8 % (95% CI, 2.4 – 7.19%). Nausea, abdominal pain were the most frequently observed signs and symptoms. Three (33.33%) ATLI patients had severe hepatotoxicity, 7 (77.77 %) recovered, 1 (11.11%) failed to respond to treatment with continued elevation of aminotransferases and 1 (11.11%) died as a result of ATLI.

Conclusion: For this cohort, ATLI incidence was higher compared to data from China and Canada, comparable with Hongkong, and Singapore but lower than Taiwan. Presence of comorbidities showed trend to increase ATLI, however, further analysis only showed those with liver and biliary diseases to be statistically significant. Larger cohort of patients is suggested.

Disclosure of Interest: None declared

P0638 BOVINE COLOSTRUM PLUS CORTICOSTEROIDS IN THE TREATMENT OF SEVERE ALCOHOLIC HEPATITIS: A PROSPECTIVE, PROOF OF CONCEPT, PHASE I TRIAL

S. S. Sidhu¹, O. Goyal¹, H. Kishore¹, A. Gupta¹

¹Gastroenterology, D.M.C. and Hospital, Ludhiana, India

Contact E-mail Address: goyalomesh@yahoo.co.in

Introduction: Severe Alcoholic Hepatitis (SAH) is defined by modified Maddrey’s Discriminant Function (mDF) ≥32 and is associated with very high short-term mortality. Corticosteroids reduce mortality in SAH patients but not to the desired extent. Bovine Colostrum is a biologic, food supplement and has immunomodulatory functions (1). Its effector constituents are immunoglobulins, growth factors (Insulin Like Growth Factor 1, 2; Transforming Growth Factor Beta), Lactoferrin and Lactoperoxidase. Lactoferrin is converted to Lactoferricin B in the stomach by pepsin which is bactericidal. Immunoglobulin G (IgG) interacts with mucosa associated lymphoid tissue, to maintain a healthy mucosal barrier and prevents gram negative bacteria and endotoxins from entering the porto-systemic circulation. Decreased endotoxemia dampens the pro-inflammatory cytokine cascade (IL 1β, IL 6, α TNF). Thus hepatocyte death and development of multisystem organ failure is averted. We aimed to study the efficacy of combination therapy of Corticosteroids and Bovine colostrum in improving mDF and reducing short-termmortality in patients with SAH.

Aims & Methods: Seventeen patients with SAH were prospectively evaluated, and 10 out of these were included. Bovine Colostrum (20 grams thrice in a day for eight weeks) and Prednisolone (40 mg once a day for four weeks, tapered over next four weeks) were administered to these patients. Serum Cytokines IL6, IL8, IL10 and TNFα were measured at 0 and 8 weeks. Paired t Test was used for analyzing the data. Data are expressed as mean ± SD. Trial was registered at Clinical Trial.gov -NCT02265328.

Results: The mean age was 41.6 ± 7.9 years and 100% were males. There was a significant improvement in mDF level from 78.1 ± 14.2 at baseline to 43.6 ± 23.8 at 8 weeks; p=0.001]. Also there was a significant change in IL6 and IL8 levels at 8 weeks (table). The survival at one month and three months was 90% and 70% respectively.

Table: Test of difference: baseline versus 8 weeks in patients with severe alcoholic hepatitis after treatment with bovine colostrum and corticosteroids.

		Paired Differences
		Mean	Std. Deviation	Std. Error Mean	95% Confidence Interval of the Difference		T	p value
	IL 8			0.09443	0.06111	0.02310		0.03791		0.01509	4.088	0.0064
	IL 6			0.05014	0.02284	0.008634		0.1620		0.1119	5.808	0.0011
	α –TNF			-0.0064	0.02964	0.01326		-0.04320		0.03040	0.4827	0.6545
	mDF			34.714	14.829	5.605		21.000		48.429	6.194	0.001

Conclusion: In patients with SAH, treatment with combination therapy of Bovine Colostrum plus Prednisolone lead to significant improvement in the liver biological functions. The 3 month survival of 70% in this study was much better than 30% survival reported prevoiusly with the use of corticosteroids alone in SAH patients (2). Therefore, this combination could be a better option for treatment of patients with SAH. Larger randomized controlled trials are required to confirm these findings.

Disclosure of Interest: None declared

P0639 CLIF-ORGAN FAILURE SCORE IS A PREDICTOR OF MORTALITY IN PATIENTS WITH ACUTE ALCOHOLIC HEPATITIS

P. Andrade¹, M. Silva¹, S. Rodrigues¹, S. Lopes¹, G. Macedo¹

¹Gastroenterology Department, Centro Hospitalar São João, Porto, Portugal

Contact E-mail Address: anapatriciarandrade@gmail.com

Introduction: Acute alcoholic hepatitis (AAH) is a distinct clinical entity in the spectrum of alcoholic liver disease and is associated to high short-term mortality. Different score systems have been used to assess the severity and predict the prognosis of patients with AAH.

Aims & Methods: Evaluate the ability of seven different score systems to predict 90-day mortality and analyse other potential predictors of mortality.

Retrospective analysis of patients admitted to our department due to AAH, between November 2009 and October 2014. The following score systems were analysed: Child-Pugh (CP), Maddrey discriminant function (MDF), model for end-stage liver disease (MELD), Glasgow alcoholic hepatitis score (GAHS), Age-Bilirubin-INR-Creatinine (ABIC), Lille score (LS) and CLIF consortium-organ failure score (CLIF-OF).

Results: We included 59 cases of AAH (78% men, mean age 47 ± 8 years). The mortality rate at 90 days was 22% (n = 13). Forty-nine percent of patients (n = 29) initiated therapy with corticosteroids. Only 28% (n = 8) of patients were complete responders (LS <0.16) while 38% (n = 11) were non-responders (LS> 0.56). Encephalopathy (p = 0.038), ascites (p = 0.013), CP score> B (p = 0.034), LS> 0.56 (p = 0.002), and a higher GAHS (p = 0.009) and CLIF-OF (p <0.001) score were significantly associated with higher 90-day mortality. In multivariate analysis, CLIF-OF score was the only one independently associated with higher mortality at 90 days (OR 2.99, 95% CI: 1.63-5.50, p <0.001).

Conclusion: AAH was associated with a 90-day mortality of 22%. The CLIF-OF score was the only score significantly associated with higher mortality at 90 days, with an OR of 2.99.

Disclosure of Interest: None declared

P0640 LIVER INJURY IN TREATED INFLAMMATORY BOWEL DISEASE PATIENTS: PREVALENCE, SEVERITY, EVOLUTION AND IMPLICATIONS FOR FURTHER TREATMENT

T. Koller¹, M. Galambosova¹, S. Filakovska¹, M. Kubincova¹, T. Hlavaty¹, J. Toth¹, A. Krajcovicova¹, J. Payer¹

¹5th Department of Internal Medicine, Sub dept. of Gastroenterology & Hepatology, Comenius University Faculty of Medicine, University Hospital Bratislava, Bratislava, Slovakia

Contact E-mail Address: koller.tomas@gmail.com

Introduction: Drug-induced liver injury (DILI) is the most common cause of acute liver injury. IBD patients might have an increased risk of DILI due to long-term treatment, multiple therapies and altered nutritional status. Any liver injury during IBD treatment might further compromise treatment choices, efficacy and overall health.

Aims & Methods: First, prospectively evaluate on-treatment prevalence, severity and evolution of liver injury in IBD patients for 6 months. Second, evaluate the impact of IBD treatment with azathioprine and/or anti- TNF on the prevalence of liver injury. Third, evaluate liver injury implications for further IBD therapy.

From 1/1/2014 to 1/6/2014 all IBD cases visiting a single center were included. Demographics, IBD status, IBD therapy and possible PSC were recorded. Liver blood tests were measured at three time points 3 months apart. Liver injury was defined as elevated ALT, GGT and ALP above 1.5 times the upper limit of normal (ULN). Two types of liver injury were predefined: transient elevation (once or twice) and persisting elevation (at all three time points). Severe liver injury was defined as ALT> 5xULN at any time. The prevalence of hepatotoxicity was compared among 4 treatment groups (no azathioprine, no anti-TNF (1), azathioprine (AZA) solo (2), anti-TNF solo (3), and combination therapy (4). Finally, we evaluated the need for change of IBD therapy caused by liver injury.

Results: 205 IBD patients were included, with median age of 40, male/female ratio 102/103, Crohn's/UC ratio 127/78, 27% with prior GI resection, 2 cases with PSC. IBD was treated with no AZA and no anti-TNF in 40 cases, azathioprine solo in 40 cases, anti-TNF solo in 63 cases and combination therapy in 62 cases. For 6 months, transient ALT elevation was observed in 18 cases (8.78%), GGT in 21 cases (10.24%) and ALP in 5 cases (2.44%). Persisting ALT elevation was observed in 3 cases (1.46%), GGT in 3 cases (1.46%) and none of ALP. Severe liver injury was observed in 1 case (0.49%) with bilirubin < ULN. The prevalence of transient liver injury among the 4 treatment groups was 5 vs. 10 vs. 12.7 vs. 9,6% for ALT and 12.5 vs. 17.5 vs. 15.9 vs. 3.2% for GGT and was not statistically different. Liver injury did not result in any change of IBD therapy.

Conclusion: Liver injury in treated IBD patients was relatively common (∼10%). However, it was mostly transient, non-severe and rarely (∼1.5%) persisted for 6 month. IBD therapy with azatioprine and/or anti-TNF did not increase the risk of liver injury. No changes of IBD treatment resulting from liver injury were needed.

Disclosure of Interest: None declared

P0641 LIPOCALIN 2 DRIVES NEUTROPHILIC INFLAMMATION IN ALCOHOLIC LIVER DISEASE

V. Wieser¹, P. Tymoszuk², C. Grander¹, M. Drach³, B. Enrich¹, L. Lichtmannegger¹, A. Bichler¹, R. Gerner¹, A. Moschen¹, T. Adolph¹, H. Tilg¹

¹Department for Internal Medicine I, ²Department for Internal Medicine VI, ³Institute of Pathology, Medical University Innsbruck, Innsbruck, Austria

Contact E-mail Address: herbert.tilg@i-med.ac.at

Introduction: Alcoholic steatohepatitis (ASH) is a severe condition in the spectrum of alcoholic liver disease (ALD) that is histologically characterised by neutrophil infiltration which correlates with mortality.¹ The underlying mechanisms of neutrophilic inflammation in the development of ALD are poorly understood and treatment options are rare.² Lipocalin-2 (LCN2) was originally found in granules of neutrophil granulocytes and termed neutrophil gelatinase-associated lipocalin (NGAL). Recently, it was shown that the liver is the predominant source of LCN2 during infections and that LCN2 is essential in liver homeostasis and experimental hepatic injury.^3,4

Aims & Methods: Our aim was to investigate the role of LCN2 in the pathogenesis of ASH. Hepatic and systemic LCN2 elevation was measured in patients with histologically ensured ASH. Furthermore, 6- to 8-week-old female C57BL/6 WT and Lcn2-deficient (Lcn2^-/-) mice were fed a Lieber-DeCarli diet containing 5% (vol/vol) ethanol or a control diet for 2 weeks ad libitum. ASH was determined by liver-to-body-ratio, GPT-elevation, steatosis and hepatic inflammation. Adoptive transfer experiments of wild-type and Lcn2^-/- neutrophils were performed to dissect the role of hepatic and neutrophil-derived LCN2 in ASH.

Results: We found a systemic and hepatic upregulation of LCN2 in patients with ASH compared to NAFLD controls, which we similarly observed in wild-type mice on a Lieber-deCarli diet. Immunocytes in hepatic tissue were the predominant source of Lcn2 expression. Lcn2^-/- mice were protected from ASH as demonstrated by diminished GPT elevation, steatosis and neutrophil infiltration. Mechanistically, we found in adoptive transfer experiments of WT and Lcn2^-/- neutrophils that cell-intrinsic (rather than hepatic) LCN2 is required for neutrophilic inflammation in ASH.

Conclusion: LCN2 drives neutrophilic inflammation in ASH in a neutrophil-intrinsic manner. Our study suggests that pharmacologic neutralisation of Lcn2 blocks neutrophil migration and protects from ASH.

Disclosure of Interest: None declared

P0642 SODIUM BENZOATE AND RIFAXIMIN ARE ABLE TO RESTORE BLOOD-BRAIN BARRIER INTEGRITY IN HE CIRRHOTIC RATS

D. Thabut¹, on. behalf of Brain Liver Pitie-Salpetriere Study Group (BLIPS), S. Mouri¹, H. EL Mourabit¹, C. Rey¹, R. Morichon¹, D. Wandum², E. Lasnier², C. Housset³, N. Weiss⁴, on behalf of Brain Liver Pitie-Salpetriere Study Group (BLIPS)

¹Hepatological ICU, La Pitie-Salpetriere Hospital, Assistance Publique - Hopitaux de Paris, ²Anatomopathological department, ³CDR Saint Antoine, Saint Antoine Hospital, Assistance Publique - Hôpitaux de Paris, ⁴Neuro-ICU, La Pitie-Salpetriere Hospital, Assistance Publique - Hopitaux de Paris, Paris, France

Contact E-mail Address: dthabut@gamil.com

Introduction: Hepatic encephalopathy (HE) is a severe complication of cirrhosis which independently influences prognosis. We previously showed an increase in blood-brain barrier (BBB) permeability in cirrhotic rats with HE. The aim of the present work was to assess the effects of sodium benzoate (Bna), a drug removing ammonia through non-urea cycle pathway, and Rifaximin (RFX), a non adsorbable antibiotic, on BBB permeability in cirrhotic rats with HE.

Aims & Methods: Three groups of rats were considered: SHAM, Bile Duct Ligation (BDL), BDL + hyperammonic dietary (BDL-NH3). In each group, rats were treated by BNa or RFX. HE was assessed using neurocomportemental testing (6 minutes tail suspension test assessing the time of immobility). NH3 levels were assessed before sacrifice. BBB permeability was assessed by IV injection of a fluorochrome (Texas Red 10kDa) before transcardial washing. Brain fluorescence was estimated by fluorimetry after right hemisphere squeezing.

Results: Mean time of immobility was longer in BDL-NH3 and BDL rats than in SHAM (p=0.0004). Ammonemia was significantly higher in the BDL-NH3 than in BDL rats, and higher in the BDL than in SHAM rats (p < 0.0001). Intra-cerebral fluorescence was significantly higher in BDL-NH3 than in BDL group, and higher in BDL than in SHAM group (p=0.029) confirming the passage of the fluorochrome through the BBB. BNa treatment significantly decreased ammonemia levels and intra-cerebral fluorescence in the BDL and BDL-NH3 rats (p < 0.04 for all) but did not modify the mean time of immobility. On the contrary, RFX treatment did not modify ammonemia levels but significantly decreased intra-cerebral fluorescence (p < 0.05) and the mean time of immobility (p=0.0004).

Conclusion: In cirrhotic rats displaying HE, BBB permeability is increased, through different mechanisms dependent and independent of hyperammonemia. BNa and RFX are effective in restoring BBB integrity in HE cirrhotic rats but only RFX is able to decrease HE in this model.

Disclosure of Interest: None declared

P0643 EVALUATION OF 13C-AMINOPYRINE BREATH TEST IN LIVER CIRRHOSIS AND HEPATOCELLULAR CARCINOMA

E. A. Abdelatti¹, I. Baghdady¹

¹Internal Medicine, Hepatology, Gastroenterology, Endoscopy, Faculty of Medicine, Menoufia University, Alexandria, Egypt

Contact E-mail Address: ehab_abdelatty@hotmail.com

Introduction: ¹³C- aminopyrine breath test (¹³C-ABT) is a simple, sensitive tool to evaluate liver function, and its results may discriminate between patients with or without cirrhosis. Also, it was previously reported that, in patients suffering from chronic liver disease of various etiologies, ¹³C-ABT can discriminate between those with chronic hepatitis and those with cirrhosis. It was reported that breath test can be used as a prognostic index in liver metastases even if concurrent biochemical liver tests are normal or only slightly disturbed.

Aims & Methods

The aim of this study: The aim of this study was to compare ¹³C-ABT results between normal subjects, patients with liver cirrhosis with and without hepatocellular carcinoma in order to identify function differences between various chronic liver diseases and to evaluate different methods of expressing ¹³C-ABT results and to maximize the information obtained from the test.

Patients and Methods: This study was carried out on 60 patients with cirrhosis and 15 normal subjects divided into three groups: group I (30 patients with liver cirrhosis), group II (30 patients with liver cirrhosis and hepatocellular carcinoma) and group III (15 healthy volunteers of matched age and sex to patient groups as a control group). ¹³C-ABT was done to all subjects of this study.

Results: The mean aminopyrine % dose/hour after 60 minutes was significantly lower in cirrhosis group and HCC group compared to control group, and it was significantly lower in HCC group compared to cirrhosis group.

The mean aminopyrine % cumulative dose after 120 minutes was significantly lower in cirrhosis group and HCC group compared to control group, and it was significantly lower in HCC group compared to cirrhosis group.

Conclusion: ¹³C-ABT is non-invasive test and easy to perform in identifying quantitatively different degrees of liver cirrhosis. ¹³C-ABT correlates well to Child classification and degree of chronic liver diseases. Liver biopsy remains the gold standard technique for the evaluation of patients with cirrhosis, its causes, and presence of hepatocellular carcinoma. ¹³C-ABT will not replace liver biopsy in diagnosing causes of cirrhosis or diagnosing of HCC. However, in patients in whom biopsy is not safe or in whom an etiologic diagnosis has been established, the aminopyrine breath test may replace serial biopsies.

Disclosure of Interest: None declared

P0644 ASSOCIATION OF GENETIC VARIANTS IN PNPLA3, MERTK, PCSK7 AND RNF7 WITH LIVER CIRRHOSIS

I. Valantiene¹², J. Kupčinskas¹², G. Varkalaitė², J. Šumskienė¹, V. Petrenkienė¹, J. Kondrackienė¹, G. Kiudelis¹, L. Kupčinskas¹²

¹ Department of Gastroenterology, Medical Academy, Lithuanian University of Health Sciences, ²Institute for Digestive Research Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania

Contact E-mail Address: irenavalantiene@yahoo.com

Introduction: Liver cirrhosis(LC) is a progressing disease commonly caused by alcohol consumption, infections of chronic hepatitis B and C and many other causes. Time period of fibrosis progression to cirrhosis varies in individual patients despite of etiology of liver cirrhosis. The search for genetic factors that could help to select patients at higher risk of developing LC is necessary. Current data indicate role of PNPLA3 gene product in lipid homeostasis and genome-wide association studies (GWAS) revealed PNPLA3 (rs738409) single-nucleotide polymorphism (SNP) association with liver diseases and fibrosis risk. A recent GWAS suggest a possible relationship between the clearance of apoptotic cells and liver fibrosis, revealing impact of MERTK (rs4374383) and RNF7 (rs16851720) SNPs. Other GWAS demonstrated that PSCK7 (rs236918) is a risk factor of cirrhosis in hereditary hemochromatosis (HH) patients. The role of these SNPs for the risk of developing LC needs to be evaluated in independent replication studies.

Aims & Methods: The aim of this study was to determine the association between the presence of PNPLA3, MERTK, PCSK7 and RNF7 SNPs and the risk of developing LC. We included 244 individuals with LC of different etiology and 498 healthy controls. The diagnosis of cirrhosis was confirmed by clinical features, liver biopsy and radiological imaging tests. PNPLA3, MERTK, PCSK7 and RNF7 SNPs in cirrhotic patients and control group were detected using real-time PCR TaqMan® method. Statistical analysis was performed using statistical software PLINK for genetic association studies. Odds ratio was adjusted for age and sex.

Results: MERTK and PCSK7 SNPs were not associated with the risk of developing liver cirrhosis (adjusted odds ratio (OD_a)-1.2, 95% confidence interval (CI₉₅) 0.96-1.52, p=0.109; OD_a-0.79, CI₉₅ (0.56-1.11), p=0.169, respectively). RNF7 SNP showed no significant association in allelic association analysis (OD_a-0.75, CI₉₅ (0.56-1.28), p=0.074), but showed lower risk of developing LC in recessive model when comparing CC vs. AA + CA genotype (OD_a-0.18, CI₉₅ (0.04-0.79), p=0.023). PNPLA3 SNP showed allelic association with higher risk of developing LC (OD_a -1.91, CI₉₅ (1.47-2.50), p=1.812*10^-8), genotypic association analysis in a recessive model GG vs. GC + CC revealed higher risk of developing LC when compared to GG genotype (OR_a-5.01, CI₉₅ (2.52-9.94), p=4.158*10^-6) and dominant model GG + GC vs. CC genotype (OR_a-1.61, CI₉₅ 1.13-2.29, p=0.09).

Conclusion: PNPLA3 and RNF7 SNPs were associated with the risk of developing LC and these genetic alterations might contribute to progression to end stage liver disease. MERTK, PCSK7 SNPs were not linked with the risk of LC.

Disclosure of Interest: None declared

P0645 EFFECT OF THE AT1 RECEPTOR ANTAGONISTS: LOSARTAN AND TELMISARTAN ON THIOACETAMIDE-INDUCED LIVER FIBROSIS IN RATS

K. Celinski¹, G. Czechowska¹, A. Korolczuk¹, G. Wójcicka², J. Dudka³, A. Bojarska⁴

¹Gastroenterology, ²Clinical Pathophysiology, ³Medical Biology, ⁴Clinical Immunology, Medical University of Lublin, Lublin, Poland

Contact E-mail Address: celinski.krzysztof@gmail.com

Introduction: Antifibrotic effects on the drugs used in the study were assessed by determining activity of biochemical parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP) and concentration of proinflammatory cytokines: interleukin 6( Il-6), interleukin beta 1( Il-beta1), tumour necrosis factor alpha ( TNF-alfa), transforming growth factor beta (TGF-beta1) and platetet-derived growth factor (PDGF-AB). Oxidative stress was evaluated by oxidised (GSSG) and reduced glutathione (GSH) levels. Moreover, activity of paraoxonase1 (PON-1), an antioxidative enzyme as well as histological inflammatory changes and fibrosis extent in the liver were evaluated.

Aims & Methods: The aim of the present study was to determine the effects of the selected AT₁ receptor antagonists (losartan, telmisartan) on liver fibrosis induced by chronic administration of thioacetamide (TAA) in rats.

Results: The experiments were performed on Wistar rats. Animals were divided into 6 groups, 8 individuals each: Control (received water, ad libitum” for 12 weeks), TAA (thioacetamide-treated rats in a dose of 300 mg/L, ad libitum” for 12 weeks), losartan (30 mg/kg bw) or telmisartan (10 mg/kg bw, intraperitoneally (ip.) once a day for 4 weeks), TAA + L (thioacetamide- treated rats, 300 mg/L, ad libitum ' for 12 weeks followed losartan in a dose 30 mg/kg/bw ip. for 4 weeks), TAA + T (thioacetamide-treated rats, 300 mg/L, ad libitum” for 12 weeks followed telmisartan in a dose 10 mg/kg bw ip. for 4 weeks).

The immunoenzymatic findings revealed a significant decrease in concentrations of the following cytokines: TNF-alpha in groups: TAA + L (P < 0.01), TAA+ T (P < 0.01), TGF-beta1 in the groups: TAA+ T (P < 0.01), TAA + L (P < 0.05) and Il-6 in group: TAA+ T (P < 0.05), as compared to the TAA group. Analysis of oxidative stress indices (GSH and GSSG) in the liver homogenates revealed statistically significant improvement: concentration of GSH in groups: TAA+ L and TAA+ T increases (P < 0.001) and concentration of GSSG in groups: TAA+ L (P < 0.05) and TAA + T (P < 0.001) decreases compared to the TAA group.

Conclusion: The present study suggest that both used drugs: losartan and telmisartan significantly inhibited the progression of hepatic fibrosis induced by TAA. Inhibitory effect of losartan and telmisartan might be associated with ability to inhibit the production of profibrotic cytokines such as TNF-alfa, TGF-beta1, IL-6 and improvement concentration parameters of oxidative stress.

Disclosure of Interest: None declared

P0646 FECAL CALPROTECTIN, SEVERITY OF LIVER CIRRHOSIS AND HEPATIC ENCEPHALOPATHY - A PROSPECTIVE SINGLE-CENTER ROMANIAN STUDY

M. A. Badea¹, C. Mihai¹, M. Dranga¹, O. Gavrilescu¹, I. Popa¹, C. Cijevschi Prelipcean¹

¹Gastroenterology, Institute of Gastroenterology and Hepatology, Iasi; University of Medicine and Pharmacy “Grigore T. Popa", Iasi, Romania

Contact E-mail Address: badea.mircea.alexandru@gmail.com

Introduction: Bacterial translocation from the gut and inflammation play an important role in the pathogenesis and complications of liver cirrhosis, including hepatic encephalopathy (HE). Calprotectin is a protein derived from neutrophilic granulocytes and it is used as an indirect marker of intestinal inflammation.

Aims & Methods: We aimed to study the correlations between fecal calprotectin (FC) concentration, the severity of liver cirrhosis and hepatic encephalopathy. We performed a prospective study which included 92 patients with liver cirrhosis between April 2014 – September 2014. Cantitative FC (by fluorescent-enzyme imuno-assay) was measured in all subjects. Patients with gastrointestinal bleeding or diarrhea, who were given proton pump inhibitors, antiplatelet therapy or antibiotics, were excluded. HE grading was measured by West Heaven criteria and the degree of liver insufficiency was assessed according to the Child-Pugh classification and Model for End Stage Liver Disease (MELD).

Results: 64.5% of patients were female and the mean age was 54.34 ± 8.72 years. The major cause for liver cirrhosis was virus C infection (65%) and the most common precipitating factors for HE were infections (51%) and constipation (42%). There were no significant differences in values of FC between the patients with different stages of liver cirrhosis according to Child-Pugh classification and MELD score (p < 0.05). The mean concentrations of FC significantly increased with aggravating hepatic encephalopathy as it follows: 84 ± 32μg/g (without HE), 144 ± 43μg/g (Grade I HE), 196 ± 56μg/g (Grade II HE), 238 ± 48μg/g (Grade III HE) and 291 ± 45μg/g (Grade IV HE), p < 0.05.

Conclusion: FC was not associated with the severity of liver disease. FC concentrations increased with aggravating HE grade. FC could be used as a simple, non-invasive and rapid test for the diagnosis and evaluation of HE severity in patients with liver cirrhosis.

Disclosure of Interest: None declared

P0647 L-CARNITINE PREVENTS LIVER FIBROSIS AND PRENEOPLASTIC LESIONS IN RAT LIVER CIRRHOSIS MODEL INDUCED BY A CHOLINE-DEFICIENT L-AMINO ACID-DEFINED DIET (CDAA) AND DIETHYLNITROSAMINE (DEN)

N. Yamamoto¹², T. Takami¹, T. Matsumoto¹, K. Fujisawa¹³, I. Saeki¹, K. Uchida¹⁴, I. Sakaida¹³

¹Gastroenterology & Hepatology, Yamaguchi University Graduated School of Medicine, ²Health Administration Center, Yamaguchi University, ³Center of Research and Education for Regenerative Medicine, Yamaguchi University Graduated School of Medicine, UBE, ⁴Human Nutrition Faculty of Nursing and Human Nutrition, Yamaguchi Prefectural University, Yamaguchi, Japan

Contact E-mail Address: nao-yama@yamaguchi-u.ac.jp

Introduction: Non-alcoholic steatohepatitis (NASH) can progress to advanced liver fibrosis and ultimately make hepatocellular carcinoma. L-carnitine is synthesized in the body from the amino acids and was proposed as the antioxidant for kidney disease and many body conditions.

Aims & Methods: The aim of this study is to investigate whether L-carnitine has any effects on the enlargement of liver fibrosis as well as preneoplastic lesions.

Methods: The effects of L-carnitine were examined using the choline-deficient L-amino acid-defined (CDAA) diet-induced NASH model. Diethylnitrosamine (DEN) 10 mg/kg was injected intraperitoneally once a week. The total study periods were 16 and 20 weeks. One group received a CDAA diet containing L-carnitine (200mg/kg/day) and DEN injection, the other group received a CDAA diet and DEN injection without L-carnitine as controls. Liver fibrosis was analyzed by Azan, Sirius–red, a-SMA, ED-1 expression. Development of preneoplastic lesions was assessed by glutathione S-transferase placental form (GST-P) expression. The change of laboratory data was analyzed. Type I procollagen, TIMP-2, aSMA,TGF-b, AFP, TNF-a, MCP-1,IL-6,EpCAM mRNA expression were analyzed using real-time RT-PCR system.

Results: After 16, 20 weeks, L-carnitine prevented liver fibrosis in a dose-dependent manner by Azan, Sirius-red expression (p < 0.05). Furthermore, L-carnitine reduced the area of GST-P positive lesions known as preneoplastic lesions (p < 0.05). Administration of L-carnitine significantly reduced levels of serum alanine aminotransferase (AST) (mean value: L-carnitine 239.3 vs Control 391.3 IU/l, p < 0.05), serum albumin (mean value: L-carnitine 4.2 vs Control 3.9 g/dl, p < 0.05). L-carnitine significantly inhibited Type 1 procollagen, TNF-a, IL-6, AFP mRNA expression (all of p < 0.05).

Conclusion: Our results indicated that L-carnitine prevented liver fibrosis and inflammation. We suggested that L-carnitine will be the new drug for NASH.

Disclosure of Interest: None declared

P0648 HEPATIC ENCEPHALOPATHY IN ICU: CEREBROSPINAL FLUID METABOLOMICS HIGHLIGHTS ALTERATION OF MULTIPLE METABOLIC PATHWAYS REPRESENTING NEW POTENTIAL THERAPEUTIC TARGETS

N. Weiss¹, B. Colsch², F. Isnard², S. Attala², M. D. M. Amador², F. Lamari³, F. Sedel⁴, C. Junot², D. Thabut⁵, on behalf of Brain Liver Pitie-Salpetriere Study Group (BLIPS)

¹Neuro-ICU, La Pitie-Salpetriere Hospital, Assistance Publique - Hopitaux de Paris, PARIS, ²iBiTec-S, Service de Pharmacologie et d’Immunoanalyse, Laboratoire d’Etude du Métabolisme des Médicaments, CEA, Saclay, ³Biochemestry, ⁴Neurology, ⁵Hepatological ICU, La Pitie-Salpetriere Hospital, Assistance Publique - Hopitaux de Paris, Paris, France

Contact E-mail Address: nic.weiss@wanadoo.fr

Introduction: Hepatic encephalopathy (HE) is a neurological complication of cirrhosis, impairing survival and quality of life. Its incidence is growing because of the improved prognosis of other complications of cirrhosis, and of the widespread use of TIPS. However, besides hyperammonemia which is often pointed out as a cause of HE, the pathophysiological mechanisms of HE remains poorly understood, which prevents the development of therapeutic strategies. To address this issue, metabolomics was used to identify dysfunction of metabolic pathways in cerebrospinal fluid (CSF) samples of cirrhotic patients suffering from HE.

Aims & Methods: The aim of this study was to detect new therapeutic targets for HE associated with cirrhosis.

Cerebrospinal Fluid (CSF) samples were collected on 14 cirrhotic patients admitted in ICU for HE, in whom infection of central nervous system has to be ruled out, and were compared to CSF of 27 control patients without any proven neurological disease. Metabolomic analysis was performed using 3 liquid chromatographies coupled to high resolution mass spectrometry methods (LC-HRMS). Informatic data processing tools were used.

Results: LC-HRMS methods led to the characterization of 150 metabolites in CSF samples of HE patients, which were mainly amino acids and organic acids. Interestingly, according to human metabolome database, 40% of those metabolites had never been retrieved were not reported as present in CSF before. HE patients could be easily discriminated from controls on the basis of metabolomicic information. Concentrations of 102 metabolites were found to be significantly altered in HE patients: metabolotypes displayed alterations in several major metabolite classes such as ammoniac, bile acids, but also amino-acids, acylcarnitines, and nucleosides. Accumulations of acetylated compounds, which could be due to a defect of the Krebs cycle, were reported for the first time in HE patients, and could constitute interesting therapeutic targets.

Conclusion: By enabling the simultaneous monitoring of a large set of metabolites in cirrhotic patients with HE, CSF metabolomics highlighted several altered metabolite pathways linked to ammonia metabolism, neurotransmission and energy metabolism. The pharmacological relevance of our findings has to be explored on animal models, as they could constitute interesting new therapeutic targets.

Disclosure of Interest: None declared

P0649 FREQUENCY OF HEPATIC HYDROTHORAX AND ITS RELATIONSHIP WITH SERUM ALBUMIN IN LIVER CIRRHOSIS PATIENTS

D. A. Kalhoro¹

¹Medicine, Dow University of Heailth Sciences Karachi, Karachi, Pakistan

Contact E-mail Address: draman_ullah2000@yahoo.com

Introduction: Cirrhosis is defined as the development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury, which leads to portal hypertension and end-stage liver disease¹. Patients with cirrhosis can develop several pulmonary conditions related to portal hypertension, including hepatopulmonary syndrome, porto pulmonary hypertension, spontaneous bacterial empyema and hepatic hydrothorax². Hepatic hydrothorax (HH) is defined as the accumulation of significant pleural effusion (>500ml) in patients with cirrhosis without primary pulmonary or cardiac disease³.

Aims & Methods: All patients with established diagnosis of decompensated chronic liver disease were included in study after getting a written informed consent.

After detailed history, thorough physical examination and routine laboratory investigations, chest X-ray chest and abdominal ultrasound were carried out in all patients to find out the presence of pleural effusion and ascites respectively. Fifty milliliters of pleural fluid was aspirated in all patients with pleural effusion using the transthoracic approach, taking ultrasound guidance wherever required. Fluid was sent for microscopic, biochemical, microbial analysis. SBEM defined when if pleural fluid with polymorphonuclear (PMN) cell count >500 cells/mm3 or positive culture with PMN cell count >250 cells/mm3 with exclusion of a parapneumonic effusion.

Results: Two hundred and six patients who met the inclusion criteria were included in the study with mean age of 41.25 ± 13.593 years. Among those 149 (72.3%) were males and 57 (27.7%) were females. Twenty three (11.2%) had hydrothorax; with right sided involvement was in 18 (78.3%) subjects, 3 (13%) had left sided while bilateral pleural effusion was found in 2 (8.7%) cases. SBEM was found in 07 (30.43%) cases. Mean serum albumin 3.125 ± 0.718 gram/dl. There was lack of correlation between serum albumin levels and hydrothorax but significant association with Child Pugh scoring system.

Conclusion: Our study highlighted the high frequency of hepatic hydrothorax having a significant association with hepatic function as assessed by Child Pugh scoring system but lack of correlation with serum albumin.

Disclosure of Interest: None declared

P0650 COMPARATIVE EVALUATION OF MELD AND CHILD-PUGH SCORES IN PROGNOSIS OF CIRRHOSIS

M. Fragaki¹, D. Sifaki-Pistolla², A. Afgoustaki¹, A. Voumvouraki¹, M. Koulentaki¹, D. Samonakis¹, E. Kouroumalis¹

¹Gastroenterology, ²Social Medicine, University of Crete Medical School, Heraklion, Greece

Contact E-mail Address: kouroum@med.uoc.gr

Introduction: The existence of reliable prognostic indices is of paramount importance in the management of cirrhosis. The MELD score and its modifications are widely used. However there have been reports that the older Child-Pugh scores are equally effective and due to their simplicity they should be used instead.

Aims & Methods: The aim therefore was to compare the prognostic accuracy of MELD,MELDNa, Child-Pugh and the corrected for Creatinine Child-Pugh score in a genetically homogeneous Cretan cirrhotic population. 195 cirrhotics (127 males, Median age 66 years) hospitalized in the past 2 years were studied and MELD, MELDNa, Child-Pugh (CP-I) and Child-Pugh adding 0-4 points according to Creatinine value (CP-II) was calculated. 142 were presented with decompensated cirrhosis.

Results: Median values were: MELD 14 (range 6-30), MELDNa 17 (range 6-33), CP-I 7 (range 5-13) and CP-II 8 (range 5-17). ROC curves for 6 and 12 months mortality showed that MELD and MELDNa were significantly better (p < 0.001) for prognosis. Areas under the curve for 6 and 12 month mortality were 0.776 and 0.766 for MELD and 0.798 and 0.786 for MELDNa. There was no difference between the two. MELD and MELDNa were also superior to CP-I and CP-II when only decompesated cirrhosis was evaluated.

Conclusion: MELD and MELDNa are better prognostic indicators of mortality in cirrhosis and should be preferred to the Child-Pugh scores.

Disclosure of Interest: None declared

P0651 KIDNEY DISFUNCTION: MAIN MARKER OF INTRA-HOSPITAL MORTALITY ASSOCIATED WITH SPONTANEOUS BACTERIAL PERITONITIS

E. Gravito-Soares¹, M. Gravito-Soares¹, C. Lérias¹, C. Sofia¹

¹Gastroenterology, Centro Hospitalar e Universitário Coimbra, Coimbra, Portugal

Contact E-mail Address: es18497@gmail.com

Introduction: Liver cirrhosis is often complicated by spontaneous bacterial peritonitis (SBP), being the kidney dysfunction common and associated with elevated mortality. Risk stratification improves prognosis. Some studies assessed predictors of severity in SBP, with controversial results.

Objective: To evaluate the predictive factors and prognosis scores in SBP.

Aims & Methods: A retrospective study of 143 consecutive episodes of SBP, between 2009 and 2014. It was evaluated the association between intra-hospital mortality and clinical and analytical variables (serum and ascitic fluid) in the diagnosis of SBP and prognostic scores: the modern acute kidney injury network (Akin) criteria, Akin progression in the first 48 hours, the simplified model of prognosis (PCR >6, age >6years and Platelet <100000) and the Model 11/22 (White blood cell >11000 and MELD >22).

Results: At admission, kidney dysfunction (Cr > 1.5 and/or urea > 30) was presented in 55.9% of patients (oligoanuric in 38.8%). The progression of kidney dysfunction in first 48 hours occurred in 50.0% of patients. The intra-hospital fatal outcome occurred in 35.0% of the cases and 80.0% in the first 30 days. The mortality associated with Akin 0, 1, 2, and 3 was respectively 10.1%, 33.3%, 57.1% and 66.7%. Oligoanuria at admission (OR 4.950; p=0.008), lower serum sodium (OR 1.094; p=0.031), higher total bilirubin (OR 1.166; p=0.002), higher serum urea (OR 1.042; p=0.001), higher Akin at admission (OR 3.144; p=0.009) and Akin progression (OR 3.607; p=0.010) were independent predictors of poor prognosis. Of prognostic scores, the progression of Akin (AUROC 0.779; p < 0.001) and Akin at admission (AUROC 0.672; p=0.001) had more accuracy to prognosis assessment of SBP, followed by the Model 11/22 (AUROC 0.641; p=0.006).

Conclusion: Kidney dysfunction is common in liver cirrhosis complicated by SBP, being the main predictor of intra-hospital mortality. The Akin has good applicability in the selection of patients with severe SBP. Therapy with albumin, vasopressors and admission in the intensive care unit should be early started in cases of kidney dysfunction at admission and progression of that within the first 48 hours.

Disclosure of Interest: None declared

P0652 SECONDARY BACTERIAL PERITONITIS IN CIRRHOSIS LIVER: A RARE OR UNDERDIAGNOSED CONDITION?

E. Gravito-Soares¹, M. Gravito-Soares¹, C. Lérias¹, C. Sofia¹

¹Gastroenterology, Centro Hospitalar e Universitário Coimbra, Coimbra, Portugal

Contact E-mail Address: es18497@gmail.com

Introduction: Secondary bacterial peritonitis (SeBP) in liver cirrhosis represents an often underdiagnosed entity with high morbidity and mortality. It early recognition improves the prognosis. Studies about this clinical condition are scarce.

Objective: To determine the frequency, clinic and prognosis of SeBP in liver cirrhosis.

Aims & Methods: A retrospective study of 250 cirrhotic patients admitted for bacterial peritonitis, between 2006 and 2014. These were selected all patients with SeBP (G1: 19patients) and compared with patients with spontaneous bacterial peritonitis (SBP) (G2: 143patients).

Results: The secondary etiology of bacterial peritonitis occurred in 7.6% of patients (male: 63.2%, mean age 60.58 ± 12.06 years). This condition was not recognized in 26.3% of cases. At admission, 47.4% showed signs of peritoneal irritation. Relatively to Runyon’s criteria, 73.3% had ≥2 criteria and 40.0% all criteria, with a sensitivity of 73.3% and specificity of 86.9%. The culture of ascitic fluid was polymicrobial in 69.2%(vs 14.3%; p < 0.001). The factors associated to SeBP were an increased LDH and Glucose < 50 in ascitic fluid (1219.79 ± 185.47 and 1632.02 vs 168.05 ± 46.7% vs 8.04%; p < 0.001). For patients with SeBP undergoing surgery (42.1%) appears to be a tendency to lower mortality (62.5% vs 72.7%; p=0.275), with a surgical timing higher in patients who did not survive (18.00 ± 23.43 vs 3.83 ± 13.91; p=0.047). The intra-hospital mortality associated with SeBP was 68.4%(vs 34.96%; p=0.005). The corticosteroids (30.0% vs 0.0%; p=0.035), higher serum LDH (292.70 ± 297.38 vs 165.33 ± 48.24; p=0.048), ascitic glucose <50 (77.8% vs 0.0%; p=0.012), higher INR (2.33 ± 1.28 vs 1.48 ± 0.33; p=0.022), higher MELD-Na (27.31 ± 8.46 vs 20.50 ± 4.23; p=0.037) and higher CLIF-SOFA (11.15 ± 4.52 vs 6.17 ± 1.60; p=0.012) were associated with higher risk of mortality. The CLIF-SOFA and MELD-Na scores were good predictors of intra-hospital mortality by SeBP (AUROC 0.859[0.000;1.000]; p=0.014 and 0.750[0.531;0.969]; p=0.047).

Conclusion: Although infrequent, the SeBP have the double mortality of SBP. The Runyon’s criteria and polymicrobial culture are good indicators of presence of intra-abdominal infection. Corticosteroid therapy, elevated INR, MELD-Na >22.5 and CLIF-SOFA >6.5 allows identify the patients at higher risk of mortality, that will benefit from more timely combined approach (medical and surgical).

Disclosure of Interest: None declared

P0653 EFFECT'S EVALUATION OF THE TREATMENT WITH CARVEDILOL VERSUS PROPRANOLOL PLUS LOSARTAN ADMINISTRATION ON HEPATIC HAEMODYNAMIC PARAMETERS IN PATIENTS WITH LIVER CIRRHOSIS

E. Tcaciuc¹, S. Matcovschi¹, D. Medvetchi-Munteanu¹, A. Tcaciuc¹, N. Nacu¹, L. Vlasov¹

¹Chair of Internal Medicine, State University of Medicine and Pharmacy “Nicolae Testemitanu", Chisinau, Moldova, Republic of

Contact E-mail Address: eugentcaciuc@yahoo.com

Introduction: Primary prevention of variceal bleeding is an important and long-debated topic in the management of patients with cirrhosis and portal hypertension. Non-selective β-blockers are recommended for primary prophylaxis of variceal bleeding in patients with oesophageal varices. Carvedilol appears to be more effective than propranolol in the treatment of portal hypertension in cirrhotic patients [1,2]. Losartan, a specific angiotensin II receptor antagonist, has beneficial effects on splanchnic hemodynamics and liver fibrosis [3].

Aims & Methods: We have examined the efficacy of the treatment with Carvedilol versus combination therapy with Propranolol plus low dose Losartan on hepatic haemodynamic parameters in patients with liver cirrhosis. The study included 64 patients with liver cirrhosis of viral HBV or HCV etiology with different cirrhotic stage. We evaluated the portal system and hepatic artery before and after 6 months of treatment using duplex Doppler ultrasonography. 34 patients (gr. 1) received Carvedilol (6.25 - 25 mg/day) and 30 patients (gr. 2) received Propranolol (30 - 120 mg/day) plus Losartan (12.5 - 25 mg/day).

Results: Administration of Carvedilol, such as administration of Propranolol and Losartan improves hepatic haemodynamics parameters in cirrhotic patients. The diameter of portal vein the same decreased in gr. 1 and gr. 2 (15.1 ± 0.6% vs 15.8 ± 0.7%, p > 0.05). Portal blood flow velocity significantly increased in gr. 2 versus gr. 1 (15.3 ± 0.8% vs 11,2 ± 0.6%, p < 0.05) and hepatic artery resistance index significantly decreased in gr. 2 versus gr. 1 (16.1 ± 0.9% vs 10.7 ± 0.8%, p < 0.05). The mean arterial pressure insignificantly decreased in both groups (p > 0.05).

Conclusion: Our study indicates that the combination treatment with Propranolol and Losartan in patients with liver cirrhosis significantly improve portal blood flow velocity and hepatic artery resistance index, probably, because Losartan contributes to decrease the intrahepatic vascular resistance in cirrhotic patients more than Carvedilol.

Disclosure of Interest: None declared

P0654 HOW TO PREDICT NONINVASIVELY THE PRESENCE OF OESOPHAGEAL VARICES?

F. Dias De Castro¹, P. Boal Carvalho¹, C. Marinho¹, J. Cotter¹²

¹Gastroenterology, Centro Hospitalar do Alto Ave – Guimarães, Portugal, Guimarães, ²Life and Health Sciences Research Institute, Universidade do Minho, Braga/Guimarães, Portugal

Contact E-mail Address: franciscadcastro@gmail.com

Introduction: Upper gastrointestinal endoscopy, despite being an invasive diagnostic procedure, is yet the gold-standard to evaluate the presence oesophageal varices in cirrhotic patients. Non-invasive methods are currently being developed in order to obviate the need for endoscopy.

Aims & Methods: The aim of our study was to assess the diagnostic accuracy of non-invasive methods that quantify hepatic fibrosis in predicting the presence of oesophageal varices.

Retrospective study including 150 patients with compensated cirrhosis of various aetiologies who performed upper endoscopy to assess the presence of oesophageal varices. Clinical, laboratorial, ultrasonography and endoscopic features were analyzed. The non-invasive methods evaluated were APRI score (AST/ platelet ratio index), SPRI score (spleen size/ platelets ratio), Fib-4 score (based on patients' age, platelet count, AST and ALT) and FibroQ (based on patients' age, platelet count, AST, ALT and INR).

The ability of the scores to predict oesophageal varices was assessed by the area under the ROC curve (AUROC).

Results: 150 patients included, 75% male with mean age 59 ± 10 years. On upper endoscopy, 120 patients (80%) had oesophageal varices. The APRI score better predicted oesophageal varices (AUROC 0.737; CI 95% 0.628-0.847), followed by Fib-4 (AUROC 0.709; CI 95% 0.606-0.813), SPRI (AUROC 0.706; CI 95% 0.596-0.816) and finally FibroQ (AUROC 0.678; CI 95% 0.572-0.785). For APRI score the best cut-off values were 0.87 with a sensitivity of 71%, specificity of 80%, positive predictive value of 93% and negative predictive value of 41%.

Conclusion: Among the studied scores, the APRI score proved to be a non-invasive method with good ability to predict the presence of oesophageal varices - an APRI value greater than 0.87 predicts the identification of oesophageal varices on endoscopy in 93% of the cases. This score, easy to use and readily accessible in clinical practice, may be valuable in a careful selection of patients with cirrhosis for early referral to upper gastrointestinal endoscopy.

Disclosure of Interest: None declared

P0655 DEVIATIONS IN PERIPHERAL BLOOD CELL POPULATIONS ARE ASSOCIATED WITH THE STAGE OF PRIMARY BILIARY CIRRHOSIS

H. Cichoż-Lach¹, E. Grywalska², A. Kowalik¹, J. Roliński², K. Celiński¹, B. Kasztelan-Szczerbińska¹

¹Department of Gastroenterology, ²Department of Clinical Immunology, Medical University of Lublin, Lublin, Poland

Contact E-mail Address: lach.halina@wp.pl

Introduction: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by progressive destruction of small size intrahepatic bile ducts leading to cirrhosis. Among genetic, environmental, also immunological factors have conclusively been shown to contribute to the pathogenesis of PBC. The role of peripheral blood cell subpopulations, particularly Treg and Th17 in PBC pathogenesis remains still uncertain.

The aim of this research was to describe the percentages and absolute counts of Th17, Treg in patients with newly diagnosed PBC and the relationships between analyzed cell subsets and selected clinical parameters (itching and the degree of PBC severity).

Aims & Methods: The frequencies of Treg and Th17 were measured by flow cytometry in 40 previously untreated female patients with PBC. The control group consisted of 20 healthy age- and sex-matched volunteers.

The diagnosis of PBC was based on the common known criteria. The degree of severity of PBC was evaluated in each patient by histologic examination.

Results: Significantly lower frequencies and absolute counts of CD4(+)CD25(+)FoxP3(+) Treg cells were found in the study group in comparison with controls (p < 0.0001).

Higher percentages and absolute counts of IL-17A(+)CD3(+)CD4(+) Th17 lymphocytes were found in the PB of PBC patients than in the control group (p < 0.0001).

Among 40 patients with PBC, 7 showed the I stage of severity- portal stage, 16 patients the II stage- periportal stage, 11 the III - septal stage, and 6 patients the IV stage – cirrhosis. Itching of the skin was observed in 18 patients with PBC.

The frequencies and absolute counts of CD4(+)CD25(+)FoxP3(+) Treg cells correlated with the degree of severity of PBC however not with itching. The correlation between frequencies and absolute counts of IL-17A(+)CD3(+)CD4(+) Th17 lymphocytes and histological stage of PBC and/or presence of itching was not observed.

Conclusion: The study demonstrates that both Treg and Th17 cells might play an important role in the pathogenesis of PBC. The reduced number of Treg cells and higher levels of Th17 cells in PBC could be responsible for the loss of immune tolerance and development of inflammatory and autoimmune process in PBC. The counts of Treg cells correlates with the degree of severity of PBC but no with presence of itching. Th17 cells did not show association between histologic stage of PBC and presence of itching.

Disclosure of Interest: None declared

P0656 RELIABILITY OF SERUM VONWILLBRAND FACTOR ANTIGEN IN PREDICTION OF ESOPHAGEAL VARICES IN PATIENTS WITH LIVER CIRRHOSIS

H. Mahmoud¹, A. Gweil¹, S. Bazeed¹, H. Fayed², M. Abdel Meguid²

¹Tropical Medicine and Gastroenterology, ²Clinical Pathology, South Valley University, Qena, Egypt

Contact E-mail Address: hassan_sedeek@yahoo.com

Introduction: Bleeding esophageal varices (OV) due to portal hypertension is one of the major complications with high mortality in liver cirrhosis. So, early detection and management is mandatory.

Aims & Methods

Aim: To evaluate the role of Vonwillbrand factor in predicting the presence of OV.

Patients and methods: 62 patients with liver cirrhosis representing different Child-Pugh classes were included. The diagnosis of liver cirrhosis was based on the combination of clinical, laboratory and US examinations. All included patients were underwent the following investigations: complete blood count, liver function tests (ALT, AST, serum bilirubin, albumin and total protein, prothrombin time (PT) and concentration (PC), INR and serum alkaline phosphatase), serum creatinine, Vonwillbrand factor antigen measurement and abdominal US. Upper endoscopic evaluation was done to detect presence or absence of varices (oesophageal or gastric) and/or PHG.

Results: 38 males and 24 females with their main age 46± 12 years old were included. Absence of OV (NO) was found in 22(35.5%) patients and presence of OV were found in 40(64.5%) patients; whom were as follow: 12(19.3%) patients were G1, 14(22.6%) were G2 and 14(22.6%) were G3. Gastric varices were found in 5(8%) patients and portal hypertensive gastropathy in 40(64.5%) patients. Serum Vonwillbrand factor-Ag level was significantly higher in patients with O.V than those without varices (p value = 0.000). Also, its level was significantly higher in patients with higher grade of OV; G3 than those with G1 or G2 (p value = 0.000). Patients with large OV including those with G2 and G3 showed statistically significant higher values of Vonwillbrand factor than those with small OV (NO and G1) (p value = 0.000). Vonwillbrand factor was independent predictor for detecting the presence of OV with good sensitivity (90), specificity (77.3) and accuracy (85.5) when its cutoff value was at 1.74. Also it was independent predictor for detecting the presence of large OV with good sensitivity (91.2), specificity (85.7) and accuracy (88.7 when its cutoff value was at 2.16.

Conclusion: Vonwillbrand factor antigen could be used as non invasive laboratory independent predictor for the presence of esophageal varices.

Disclosure of Interest: None declared

P0657 THE EFFECT OF NON-SELECTIVE BETA-BLOCKERS ON SURVIVAL IN DECOMPENSATED LIVER CIRRHOSIS PATIENTS

I. Girleanu¹, A. Trifan¹, C. Cojocariu¹, A. M. Singeap¹, A. Rohozneanu¹, S. Chiriac¹, C. Stanciu¹

¹Gastroenterology, University of Medicine and Pharmacy Iasi, Romania, Iasi, Romania

Contact E-mail Address: gilda_iri25@yahoo.com

Introduction: Recent studies evaluating outcomes associated with nonselective beta-blockers (NSBB) in cirrhosis have yielded mixed results (1). Due to their effect on cardiac output and on intestinal permeability, NSBB have been hypothesized to increase the risk of mortality especially in advanced liver disease (2). The aim of this study was to assess the effect of NSBBs on survival in decompensateted liver cirrhosis patients.

Aims & Methods: Liver cirrhosis patients who were admitted to our tertiary center from January 2005 to December 2005 were enrolled, and survival data until December 2014 was measured. Stratified randomization according to the Child–Pugh class and age was done and a total of 702 patients were divided into beta-blocker group (Propranolol, 40 mg/day) and non beta-blocker group. Overall survival and predictors of mortality were evaluated.

Results: There were 702 cirrhotic patients included in the study, mean age 55.82 ± 11.52 years, 392 (55.8%) males. Out of these 340 patients (48.8%) received NSBB treatment. There was no significant difference of survival (P = 0.321) and infection free survival (P = 0.910) between two groups. Two subgroups analyses according to the Model of End Life Disease (MELD) (MELD < 15, and MELD ≥ 15) also showed no significant difference of survival and infection free survival. Significant univariate predictors of death were age, Child–Pugh score, MELD score, prothrombin time, total bilirubin, albumin, and aspartate aminotransferase. The independent predictors of mortality were Child–Pugh score, and MELD score. Presence of esophageal varices was not predictor of mortality.

Conclusion: Non-selective beta-blockers have no effect on survival and infection free survival in cirrhotic patients. That means that NSBBs may not be used for the purpose of improving survival in decompensated liver cirrhosis patients.

Disclosure of Interest: None declared

P0658 TERLIPRESSIN-INDUCED HYPONATREMIA IN CIRRHOTIC PATIENTS WITH VARICEAL BLEEDING

I. Girleanu¹, A. Trifan¹, O. C. Stoica¹, C. Cojocariu¹, A. M. Singeap¹, C. Sfarti¹, C. Baluta¹, C. Stanciu¹

¹Gastroenterology, University of Medicine and Pharmacy Iasi, Romania, Iasi, Romania

Contact E-mail Address: gilda_iri25@yahoo.com

Introduction: Terlipressin is frequently used in acute variceal bleeding due to its important effect on vasopressin V1 receptors. Terlipressin has agonistic effects on the V1 receptor and partial agonistic effects on renal vasopressin V2 receptors. However, its effects on serum sodium concentration are controversial. The aim of this study was to examine the effects of terlipressin on serum sodium concentration in cirrhotic patients with variceal bleeding.

Aims & Methods: All consecutive cirrhotic diagnosed with variceal bleeding treated with terlipressin were investigated Terlipressin induced hyponatremia was defined as a decrease in serum sodium (Na) level of >5 mEq/L from the baseline level. Main outcome measure was fall in Na level during and up to 5 days post therapy.

Results: The study included 214 patients (mean age, 54.3 ± 10.7 y) with male predominance (60.7%). Median Na pretreatment was 130.0 ± 6.5 mmol/L and 126/214 (58.87%) had existing hyponatraemia. Serum sodium level was at the baseline 130.0 ± 6.5 mmol/L and 131.4 ± 6.2 mmol/L after 5 days of terlipressin treatment (P =0.758) in all patients. Changes in serum Na levels from baseline were 0.2 ± 1.2 whereas the frequencies of terlipressin-indiced hyponatremia was 6.07% (13 patients). Occurrence of hyponatremia was related neither to duration or dosage of terlipressin treatment but with the severity of the underlying chronic liver disease. No complications of hyponatremia were observed.

Conclusion: Terlipressin-induced hyponatremia was uncommon in cirrhotic patients with variceal bleeding. Hyponatremia was related with the severity of the underlying liver cirrhosis.

Disclosure of Interest: None declared

P0659 ANTIVIRAL THERAPY IMPROVES POST-TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT SURVIVAL IN PATIENTS WITH HEPATITIS B VIRUS-RELATED LIVER CIRRHOSIS

J. Lin¹, B. Wei¹, C. Tang¹

¹Department of Gastroenterology, West China Hospital, Sichuan University, P. R. China, Chengdu, China

Contact E-mail Address: shcqcdmed@163.com

Introduction: Antiviral treatment has been shown to be effective in patients with hepatitis B virus (HBV)-related decompensated cirrhosis. However, the effect of antiviral therapy in the subset of post-transjugular intrahepatic portosystemic shunt (TIPS) patients with HBV-related decompensated cirrhosis is uncertain.

Aims & Methods: From January 2007 to December 2012, a total of 211 patients who underwent TIPS for variceal bleeding or refractory cirrhosis due to HBV-related cirrhosis were included in this prospective cohort study. Of these, 124 (58.7%) patients started antiviral therapy before or after TIPS foremed the antiviral group, and the remaining 87 (41.3%) patient formed untreated group. The primary endpoint was transplant-free survival. The secondary endpoints included recurrent variceal bleeding, occurrence of complications and shunt dysfunction.

Results: The baseline characteristics were comparable in the two groups. Antiviral used included adefovir (n=49), entecavir (n=36), lamivudine (n=29), telbivudine (n=2), combination of lamivudine and adefovir (n=7), and combination of lamivudine and telbivudine (n=1). Among the patients in antiviral group, 20 died during the study period, as compared with 33 patients in the untreated group. Patients in antiviral group had a significantly better transplant-free survival (P=0.004, by the log-rank test). The cumulative survival rates at 1, 2, and 3 year were 93.742%, 89.466% and 85.671% in the antiviral group, and 86.207%, 71.034% and 64.284% in the untreated group, respectively. Patients who started antiviral therapy before TIPS had better survival than post-TIPS antiviral patients. The use of antiviral therapy, age and MELD score were the independent predictors for survival. The incidence of HCC tend to be lower in the antiviral group, and the difference was borderline significant (P=0.053). The cumulative incidence of HCC at 1, 2, and 3 year were 2.639%, 6.291% and 9.836% in the antiviral group, and 3.949%, 14.970% and 19.118% in the untreated group, respectively. The incidence of variceal rebleeding and primary shunt patency were not significantly different between the two groups (P=0.126, P=0.330 respectively).

Conclusion: Antiviral interventions improves survival in post-TIPS patients with HBV-related decompensated cirrhosis, especially in those with early treatment. This result underscore the use of antivirals as a mandatory etiology treatment in patients who underwent TIPS.

Disclosure of Interest: None declared

P0660 HIGH INCIDENCE OF RESISTANCE TO THIRD-GENERATION CEPHALOSPORINS IN CIRRHOTIC PATIENTS IN A PORTUGUESE GASTROENTEROLOGY DEPARTMENT

J. Carmo¹, M. A. Túlio¹, S. Marques¹, M. Bispo¹, M. A. Pessanha², C. Toscano², C. Chagas¹

¹Gastroenterology, ²Microbiology, Hospital Egas Moniz, Lisboa, Portugal

Contact E-mail Address: joanavcarmo@gmail.com

Introduction: Bacterial infections are one of the main causes of decompensation in cirrhosis and contribute significantly for morbidity and mortality in cirrhotic patients.

Aims & Methods

Aims: Characterize the infections and microbiological agents in patients admitted for decompensated cirrhosis in a Gastroenterology Department in Portugal. Analyze the antibiotic therapy used in these patients and its effectiveness.

Methods: Retrospective analysis of incoming patients admitted for decompensated cirrhosis in 2013 in a Portuguese Gastroenterology Department. Clinical/demographic (cirrhosis’ etiology, Child-Pugh score, previous hospitalizations, antibiotic therapy, inpatient outcome) and microbiologic (infections’ focus, agents and its sensibility profile) data were analysed.

Results: 95 patients were admitted for decompensated cirrhosis. Bacterial infections were the cause of decompensation in 54% (n=51). Average age: 67 years; >50% with advanced (Child-Pugh C, 71%) and alcoholic cirrhosis; average time of hospitalization: 11 days. We diagnosed 30 cases of health care-associated infections, 16 community-acquired infections and 5 nosocomial infections. The most frequent infection was urinary tract infection (47%, n=24), followed by spontaneous bacterial peritonitis and respiratory tract infections, with the same incidence (22%, n=11). The most commonly used empirical antibiotic therapy was third-generation cephalosporins (35%, n=18), amoxicillin/clavulanic acid (22%, n=11) and quinolones (17%, n=9). In 45% of the patients, no agent was isolated. In the remaining patients, 36 agents were isolated. Two thirds were Gram negatives and E. coli was the most frequent. 40% of the agents were resistant to third-generation cephalosporins. Ten agents were multiresistant bacteria (four extended-spectrum β-lactamase-producing enterobacteriaceae and one vancomycin-resistant enterococcus). Hospitalization in the previous 90 days was related with infection by multiresistant agents (p <0.05).

Conclusion: The difficulty in obtaining a microbiological isolate, makes antibiotic choice more challenging. Although third-generation cephalosporins continue to be a first-line antibiotic in patients admitted for decompensated cirrhosis, we found a significant resistance rate to these antibiotics. In the choice of antibiotic therapy, hospitalization in the last 90 days should also be considered because multiresistant bacteria involvement is more probable.

Disclosure of Interest: None declared

P0661 LIVER CIRRHOSIS DOES NOT IMPAIR THE SHORT-TERM OUTCOME IN PEPTIC ULCER BLEEDING

J. M. Petersen¹, A. Krag¹, O. B. Schaffalitzky de Muckadell¹, S. B. Laursen¹

¹Department of Medical Gastroenterology, University of Southern Denmark, Odense, Denmark

Contact E-mail Address: jmpetersen@health.sdu.dk

Introduction: Variceal bleeding in patients with liver cirrhosis is associated with a considerable mortality around 10-20%. The outcome of peptic ulcer bleeding (PUB) in patients with liver cirrhosis compared to patients without cirrhosis has not been studied in detail.

Aims & Methods: Data were prospectively collected from consecutive patients admitted with PUB at our department through an 11-year period. We compared patient characteristics, bleeding episode, and outcome between patients with liver cirrhosis and patients without cirrhosis.

Results: A total of 1002 patients were admitted with PUB during the period of inclusion. Thirty-five (3.5%) patients had cirrhosis. Compared to patients without liver cirrhosis patients with cirrhosis were younger (mean age: 58 vs 73 years; p < .001), were more often males (74% vs 54%; p=.02), more frequently had hemodynamic shock at time of admission to hospital (46% vs 29%; p=.039), a higher ASA-score (p=.005), high intake of alcohol (79% vs 12%; p<.0001), high frequency of daily smokers (78% vs 32%), and a longer duration of admission to hospital (mean: 7.5 vs 5.6 days; p=.018). However, patients with cirrhosis was only rarely diagnosed with cardiac disease (5.7% vs 42%; p<.0001) and only few had intake of aspirin (14% vs 50%; p=.001). There were no differences in B-hemoglobin (5.1 vs 5.4mmol/L), duodenal ulcer location (71% vs 57%), high-risk stigmata of bleeding (37% vs 39%), rate of rebleeding (20% vs 16%), or in-hospital mortality (8.6% vs 5.3%).

Conclusion: Patients with PUB and cirrhosis are younger and only rarely diagnosed with cardiac comorbidity compared with PUB-patients without cirrhosis. Nevertheless, patients with cirrhosis and PUB have a high level of non-cardiac comorbidity and negative lifestyle factors that may explain the lack of difference in short-term mortality. Beside a difference in rate of hemodynamic shock, that may be explained by impaired cardiac response in cirrhotics, the character and severity of PUB seem similar in both groups of patients.

Disclosure of Interest: None declared

P0662 THE PREVALENCE, PROGNOSIS AND OUTCOME OF SIRS, SEPSIS AND SEVERE SEPSIS IN PATIENTS WITH CIRRHOSIS OF THE LIVER

S. Sheetal¹, K. T. Shenoy²

¹Neurology, Pushpagiri Medical College and Hospital, Tiruvalla, ²Gastroenterology, Sree Gokulam Medical College and Research Foundation, Venjaramoodu, India

Contact E-mail Address: drktshenoy@gmail.com

Introduction: Cirrhotic patients are particularly susceptible to bacterial infections. Once an overt infection occurs, it may lead to systemic inflammatory response syndrome (SIRS)/sepsis which can precipitate hypotension (severe sepsis), renal dysfunction, encephalopathy, and coagulopathy, that is, multi organ failure. We studied sepsis and severe sepsis in a tertiary hospital in S India.

Aims & Methods

Aims: To estimate the prevalence of SIRS, sepsis and severe sepsis in patients with cirrhosis of liver and to study the pattern of clinical presentation; to assess the correlation between CRP and clinical outcomes in these patients and to elucidate the prognostic factors related to progression of disease and/ or death.

Methods: 70 patients with cirrhosis were prospectively evaluated at baseline, 3, 6, 9 and 12 months of follow up for sepsis, severe sepsis and septic shock and complications related to cirrhosis such as SBP, hepatorenal syndrome and mortality. Sepsis was diagnosed by CRP levels and culture of blood and urine. Data were analysed for study variables and survival.

Results: 70 patients (64 males and 6 females)in the age group of 30 -80 years were studied. 32.9% belonged to the 40-50 year age group. The mean age was 55.6 ± 10.1 years.The clinical presentation of patients with cirrhosis were as follows: melena in 57.1%; hematemesis and abdominal distension in 39 patients (55.7%). Alcohol consumption accounted for cirrhosis in 72.9%, Hepatitis B infection and concomitant alcohol intake in 11.4%, isolated Hepatitis B infection in 2.9% and Hepatitis C infection in 1.4%. No cause could be identified 10%.2 patients (2.9%) had SIRS, 12 patients had sepsis (17.1%), 6 had severe sepsis (8.6%), and 7 had septic shock (10%). Spontaneous bacterial peritonitis accounted for 48% of infections, followed by equal percentage of urinary tract infection, pneumonia and cellulitis (16% each), bacteremia was seen in 4%. CRP was positive in 25 patients (35.7%) and negative in 45 (64.3%). 29 patients (41.4%) hepatic encephalopathy; 18 had hepato renal syndrome (25.7%) and a total of 24 patients expired (34.3%). A statistically significant correlation was noted between CRP positivity and sepsis ( p value- 0.000), severe sepsis (p value -0.001) and septic shock (p value -0.007), SBP (p value 0.000), UTI (p value -0.014) pneumonia (p value -0.014), hepatic encephalopathy (p value 0.000), hepatorenal syndrome (p value 0.000) and death (p value 0.000). A statistically significant correlation with mortality was established for severe sepsis (p 0.016), septic shock (p-0.000), SBP (P value 0.000), UTI (p 0.012), hepatic encephalopathy and hepatorenal syndrome. (p value- 0.000). 12 patients had SBP during their initial presentation. The prevalence of SBP at 3, 6,9,12 months was 7(10%), 8(11.4%), 3(4.3%), 5(7.1%). 24 patients had expired at the end of 1 year and 4 were lost to follow up.malaena was the presenting feature in 40 patients.

Conclusion: There was high prevalence of sepsis and severe sepsis with a high mortality at 1 year of follow up.

Disclosure of Interest: None declared

P0663 THE EFFECT OF LACTULOSE, RIFAXIMIN, L-ORNITHINE L-ASPARTATE, THEIR COMBINATION ON MINIMAL HEPATIC ENCEPHALOPATHY TREATMENT

K. Elnoemany¹, A. Alghoraieb¹, N. shebl¹, T. salman¹, E. reweisha¹, on behalf of National Liver Institute

¹Hepatology, National Liver Institute, Shebin Elkom, Egypt

Contact E-mail Address: dr_kareemn@yahoo.com

Introduction: Minimal hepatic encephalopathy (MHE) is observed in 84% of patients with liver cirrhosis without the presence of overt HE. It adversely affects health-related quality of life (HRQOL).

Aims & Methods

Aim: to compare lactulose, rifaximin, L-Ornithine L-Aspartate (LoLa), their combination on MHE treatment and HRQOL.

Methods: After screening for MHE, 126 patients with MHE were assigned for the following treatment regimens; 30-60 ml lactulose twice daily (n=31), 200 mg rifaximin thrice daily (n=32), 6 g LoLa thrice daily (n=32), and combined therapy (n=31). All patients were assessed by critical flicker frequency (CFF), number connection test (NCT), serial dotting test (SDT), ammonia and sickness impact profile (SIP) questionnaire at baseline and two consecutive months.

Results: By repeated measure ANOVA test, there was favorable treatment induced changes in all groups concerning the three consecutive values of CFF (36.6 vs. 31.33 vs. 38.09 Hz; p=0.001 except LoLa; p=0.167), NCT (-2.5 vs. -1.15 vs. -0.9 SD; p=0.001), SDT (-2.6 vs -1.27 vs. -1.07 SD; p=0.001), ammonia (85.75 vs. 76.93 vs. 69.65 mmol/l; p=0.001 except rifaximin; p=0.50) and SIP questionnaire score (24.75 vs. 16.1 vs. 16.31; p=0.001). The overall comparison of all groups was insignificant (p > 0.05). The predictors of MHE were age (odds =1.069), bilirubin (odds =5.254), albumin (odds =0.163), INR (odds =73.816) and Child-Pugh score (odds =2.459).

Conclusion: Lactulose, rifaximin, LoLa, their combination are the same on MHE treatment and HRQOL.

Disclosure of Interest: None declared

P0664 NUTRITIONAL STATUS OF CIRRHOTIC PATIENTS IN A REFERRAL CENTRE FOR LIVER DISEASE IN CRETE GREECE

D. Sifaki-Pistolla¹, A. Markaki², J. Galanos², M. Christodoulaki², A. Mantaka³, A. Augoustaki³, V. Zafiropoulos², E. Kouroumalis³, M. Koulentaki³

¹Clinic of Family and Social Medicine, Faculty of Medicine University of Crete, Heraklion, ²Nutrition & Dietetics, Technological Educational Institute of Crete, Sitia, ³Gastroenterology, University Hospital Heraklion Crete, Heraklion, Greece

Contact E-mail Address: mkoulentaki@yahoo.gr

Introduction: Prognosis of cirrhotic patients is related to their nutritional status even in the compensated stages. Protein-energy malnutrition is not always recognized by attending physicians.

Aims & Methods: We aimed to assess the nutritional status of Greek cirrhotic patients, followed at the Department of Gastroenterology and Hepatology of the University Hospital of Heraklion (Crete, Greece).

We studied 101 cirrhotic patients (48 compensated, 52 females), median age 67.07 (31-88) years and 71 healthy controls (35 females), median age 66.04 (37-94) years. Cirrhosis etiology was viral hepatitis 43 pts. (23 HCV, 20 HBV), 20 non alcoholic steatohepatitis (NASH), 14 primary biliary cirrhosis (PBC), 5 autoimmune hepatitis (AIH), 14 alcoholic and 3 cryptogenic. Patients with hepatic encephalopathy or active alcohol drinking were not included in the study. MELD score was calculated to assess the severity of liver disease. Nutritional assessment included Body mass index (BMI), anthropometry, handgrip strength, bio-impedance analysis (BIA), the mini nutritional assessment (MNA) questionnaire, the Subjective Global Assessment (SGA) and the Malnutrition Universal Screening Tool (MUST) evaluation.

Comparisons were made by Student’s T-test for continuous variables. Fisher’s exact probability test and the χ2 test for the analysis of categorical variables. Spearman’s rank coefficient was used for correlations. All tests were made at a 0.05 level of significance.

Results: Median MELD score was 14.6 (SD 2.43),

Parameters with significant differences between groups are shown in the table.

MUST score and SGA score also differ significantly between groups (p < 0.001). A strongly positive correlation between MELD & MNA (rho=0.87, p=0.01) and strongly negative correlations between MELD and phase angle (ϕ) (rho= -0.80, p=0.01) and MELD & handgrip (rho=-0.79, p < 0.001) were found.

Parameters	PatientsMean (SD)	ControlsMean (SD)	p value
BMI	29.85 (5.93)	28.08 (5.68)	0.04
MAMC	21.68 (3.29)	23.11 (3.44)	0.007
Handgrip (kg)	27.26 (11.61)	42.90 (10.34)	0.002
Handgrip <85%	70%	30%	<0.001
(BIA) ICW%	45.41 (10.58)	48.93 (9.81)	0.04
(BIA) BCM%	46.21 (11.74)	51.61 (11.55)	0.01
(BIA)Muscle mass%	37.13 (8.71)	42.90 (10.34)	0.02
(BIA) Phase angle (ϕ)	4.9 (1.15)	5.67 (1.22)	<0.001
MNA	21.78 (3.94)	23.39 (3.91)	0.01

Conclusion: BMI and most anthropometric measurements, except MAMC, did not detect the protein malnutrition of Greek cirrhotic patients. MUST, SGA, MNA, BIA, and handgrip were found all sensitive tools for its detection, the last three also correlating with the severity of liver disease.

Disclosure of Interest: None declared

P0665 TERLIPRESSIN AND ALBUMIN IS AN EFFECTIVE TREATMENT IN PATIENTS WITH CIRRHOSIS AND HEPATORENAL SYNDROME TYPE 2

M. Nguyen-Tat¹², J. Jäger¹, E. Götz¹, J. Ahrens¹, J. Rey³, V. Sivanathan¹, M. Wörns¹, A. Hoffman³, P. R. Galle¹, J. U. Marquardt¹

¹Cirrhosis Center Mainz (CCM), ²Department of Medicine I, University Medical Center, Mainz, ³Internal Medicine II, Horst-Schmidt-Kliniken, Wiesbaden, Germany

Contact E-mail Address: marquarj@uni-mainz.de

Introduction: Untreated hepatorenal syndrome (HRS) is associated with a very bad prognosis in patients with advanced liver cirrhosis. Hepatorenal syndrome is subdivided into a HRS type 1 with a rapid-progressive loss of renal function and a HRS type 2, characterized by chronic ascites and persistently but moderately elevated renal parameters. While treatment with terlipressin and albumin improves renal function in patients with type 1 HRS, it is less clear if this treatment is effective in type 2 HRS.

Aims & Methods: Aim of this study was to examine the effect of treatment with terlipressin and albumin on renal function and survival in patients with HRS type 2.

All patients who presented to our center between April 2013 and February 2015 with a first episode of HRS type 1 or type 2 and who were treated with terlipressin and albumine were included in this observational study. Relevant clinical and laboratory parameters were prospectively examined – e.g. HRS type, baseline liver function, patient characteristics, side effects, renal function and overall survival as well as survival free of renal replacement therapy or liver transplantation.

Results: Overall 80 patients with liver cirrhosis and a first episode of HRS were prospectively followed over a median of 76 days. Most patients had advanced liver disease (Child-Pugh C: 67; 84%). 29 patients had HRS type 1, while 51 patients were diagnosed with a type 2 HRS (36%; 64%). Baseline patient characteristics such as etiology of cirrhosis, Child-Pugh stage, degree of ascites or hepatic encephalopathy grade were similar in both subgroups. As expected, median serum creatinine concentration was significantly higher in patients with HRS type 1 (3.1 vs. 2.4 mg/dl; p=0.0003). Complete or partial response to terlipressin treatment was observed in 38 and 4 of 80 patients (CR: 48%; PR: 5%). Overall response rates were not significantly different between patients with HRS type 2 and type 1 (52% vs. 53%; p=0.92). Overall survival and survival free of renal replacement therapy or liver transplantation was comparable too. Response to terlipressin treatment in HRS type 2 was associated with a significantly improved median survival (p < 0.0001).

Conclusion: Terlipressin in combination with albumine is effective in HRS type 2 – a response to treatment can be expected in approximately 50% of patients. Response to treatment is an important prognostic indicator as it is associated with improved survival.

Disclosure of Interest: None declared

P0666 SCREENING FOR HEPATOPULMONARY SYNDROME IN CIRRHOTIC PATIENTS: DIAGNOSTIC APPROACH AND CLINICAL CORRELATIONS

M. Fragaki¹, D. Samonakis¹, S. Koukouraki², D. Sifaki-Pistolla³, M. Koulentaki¹, E. Matrella¹, E. Kouroumalis¹

¹Department of Gastroenterology & Hepatology, ²Department of Nuclear Medicine, University Hospital of Heraklion, ³Department of Social Medicine, University of Crete, Heraklion, Greece

Contact E-mail Address: mgfragaki@yahoo.gr

Introduction: Hepatopulmonary syndrome (HPS) affects 10-30% of patients with cirrhosis and/or portal hypertension, but is frequently underdiagnosed. It is characterized by the triad of advanced liver disease, arterial hypoxemia and intrapulmonary arteriovenous shunting in absence of primary cardiopulmonary disease. The aim of the study was to screen cirrhotics with arterial blood gases and albumin perfusion scan, identify those fulfilling the classic HPS criteria and correlate with clinical parameters.

Aims & Methods: Data on 102 patients presenting to the Liver Clinic or hospitalized in the Gastroenterology wards within one year and were analyzed. Clinical, metabolic and biochemical variables were measured, as well as MELD MELDNa, and Child-Pugh score, arterial blood gases, alveolar-arterial oxygen gradient [P(A-a)O2] were recorded. All patients underwent Technetium 99m-macroggregated albumin perfusion lung scan (Tc-MAA) and a subset of those had contrast-enhanced transthoracic echocardiography with saline (microbubbles >10μm in diameter). Diagnosis of HPS was based on the presence of the quantitative index Tc-MAA ≥ 6% and a [P(A-a)O₂] ≥ 15mmHg ( ≥20 mmHg for patients over > 64 years).

Results: 61 were male (59.8%) .Median age 66.5 years (range, 31-84). Mean BMI was 27.5 (SD 4.7) and median MELD was 12 (range, 6-22). 66 patients presented with decompensated cirrhosis, 10 with HCC. The mean P(A-a)O2 and P02 were 24 (SD14.1) and 81.3 (SD13.6) mmHg respectively. Patients with concomitant respiratory disease had all P(A-a)O2 > 20mmHg and were not evaluated further for HPS. Average P(A-a)O2 did not differ according to decompensation status (P=0.6).

Quantitative median index in the Tc-MAA was 6% (range, 1-17). Diagnosis of HPS was made on 24/94 patients. In 8 patients the Tc-MAA scintigraphy could not be interpreted. In the multivariate analysis only the quantitative index was significant for the diagnosis of HPS. ( p= 0.001, OR; 95% CI: 7,05; 2,27-21,87)

Three patients with positive bubble echo had all quantitative index > 9% in Tc-MAA. The latter index was not statistically correlated with P(A-a)O2, PO2, or MELD score (p=n.s). Five patients died over the short follow-up period with no significant differences in survival time according to P(A-a)O2 or the results of Tc-MAA.

Conclusion: Tc-MAA is a useful screening tool in patients with arterial hypoxemia for complications as HPS which is a frequent complication of cirrhosis. Qualitative analysis is not reliable with false negative and positive results. Quantitative analysis should always be performed.

Disclosure of Interest: None declared

P0667 SOLUBLE CD163 (SCD163) IS A MARKER OF INFECTION IN PATIENTS WITH CIRRHOSIS AND ACUTE DECOMPENSATION AND AN INDEPENDENT PREDICTOR OF THE SHORT-TERM MORTALITY

T. Tornai¹, D. Tornai², Z. Vitalis¹, I. Tornai¹, P. Antal-Szalmas², M. Papp¹

¹Institute of Medicine, Department of Gastroenterology, ²Department of Laboratory Medicine, University of Debrecen, Clinical Center, Debrecen, Hungary

Contact E-mail Address: papp.maria@med.unideb.hu

Introduction: sCD163 is shed from macrophages in response to inflammatory stimuli and suggested to modulate the inflammatory response. We aimed to determine the predictive potential of sCD163 levels in the determination of disease phenotype and disease course in a prospective referral cirrhotic cohort.

Aims & Methods: 378 consecutive patients with cirrhosis(LC) of different etiology (54.0% males, 70.6% alcoholic) and severity (ChildA/B/C: 39.2/38.1/22.7%, acute decompensation[AD]: 48.9%) were enrolled and followed until death or last attendance. Serum levels obtained at enrollment were assayed for sCD163 by ELISA. Detailed clinical phenotypes regarding first decompensation event (ascites formation, variceal bleeding[VB], hepatic encephalopathy or systemic bacterial infection[INF]), development of hepatocellular carcinoma[HCC] and mortality were determined prospectively during the follow-up (median[IQR], 778[182-1720] days). Control group comprised 150 healthy subjects (HC).

Results: Serum levels of sCD163 were significantly higher in patients with LC compared to HC (median, 3724 vs. 1104 ng/ml,p < 0.001). In LC, sCD163 levels were associated to disease severity, as rated by the Child-Pugh stage (p < 0.001) but not to the presence of varices or prior VB. In non-AD patients, sCD163 levels were not able to predict the advent of the first decompensation events, development of HCC and also not the long-term mortality. In patients with AD episodes, sCD163 levels were significantly higher compared to non-AD patients but only in the presence of INF (AD-INF: 4969, AD-NON-INF: 3497 and NON-AD: 3471 ng/ml, p < 0.001 for both). Furthermore, during INF episodes (n=119), sCD163 levels were significantly higher in those complicated with organ failure (31%) and increased gradually according to ACLF grade (No-ACLF: 4121, ACLF gr1: 7335, gr2: 7490, gr3: 12610 ng/ml, p=0.001). Rate of 28-day mortality was higher among patients with sCD163 level > 7110 ng/ml compared to those with ≤ 7110 ng/ml (46.5% vs. 15.8%, p < 0.001). This cut-off level of sCD163 was associated with a shorter time to death (pLogRank < 0.001) in Kaplan-Meier analysis and was identified as an independent predictor in multivariate Cox- regression model (HR:2.91, 95%CI:1.34–6.32,p=0.007) comprising age, gender, etiology, co-morbidity and MELD score as covariates.

Conclusion: Admission sCD163 levels may be an additional help in rapid identification of patients with high-risk for death during AD epsiodes complicated with INF in LC.

Disclosure of Interest: None declared

P0668 SUSTAINED VIROLOGIC RESPONSE RATE OF 96% IN HCV GENOTYPE 1A-INFECTED PATIENTS TREATED WITH OMBITASVIR/PARITAPREVIR/R AND DASABUVIR WITH RIBAVIRIN

H. Wedemeyer¹, P. Pockros², S. S. Lee³, E. Gane⁴, C. Moreno⁵, S. Strasser⁶, V. De Ledinghen⁷, A. Maieron⁸, W. Xie⁹, R. Trinh⁹, Y. Luo⁹, F. Tatsch⁹, V. Rustgi¹⁰

¹Medizinische Hochschule Hannover, Hannover, Germany, ²Scripps Clinic, La Jolla, United States, ³University of Calgary, Calgary, Canada, ⁴Liver Unit, Auckland City Hospital, Auckland, New Zealand, ⁵CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium, ⁶AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown NSW, Australia, ⁷Hopital Haut Leveque, CHU Bordeaux, Pessac, France, ⁸Elisabeth Hospital, Linz, Austria, ⁹AbbVie Inc., North Chicago, ¹⁰Thomas E. Starzl Transplantation Institute, Pittsburgh, United States

Contact E-mail Address: fernando.tatsch@abbvie.com

Introduction: The interferon-free 3 direct-acting antiviral (3D) regimen of ombitasvir (an NS5A inhibitor), paritaprevir (an HCV NS3/4A protease inhibitor identified by AbbVie and Enanta, boosted with ritonavir [r]) and dasabuvir (a non-nucleoside NS5B RNA polymerase inhibitor) is approved to treat patients infected with HCV genotype (GT) 1. Using pooled data from four phase 3 studies in treatment-naïve and prior pegIFN/RBV-experienced patients with GT1a infection, with or without cirrhosis, we report the safety and efficacy in patients who received the label-recommended 3D regimen plus ribavirin (RBV).

Aims & Methods: Genotype 1a-infected patients from the PEARL-IV, SAPPHIRE-I, SAPPHIRE-II, and TURQUOISE-II studies were included in this post-hoc analysis. Efficacy was assessed by the proportion of patients achieving sustained virologic response (HCV RNA <25 IU/mL) 12 weeks after completion of treatment (SVR12). Per the US Prescribing Information and European SmPC, the label-recommended regimen for GT1a infection is 3D + RBV for 12 weeks in non-cirrhotic patients, and 3D + RBV for 24 weeks in patients with cirrhosis. Adverse events (AEs) and laboratory measures are reported for all patients receiving the label-recommended regimen.

Results: Among 714 HCV GT1a-infected patients treated with the label-recommended 3D + RBV regimen, 64% were male, 33% were treatment-experienced, 17% had cirrhosis, and 85% had baseline viral loads ≥800,000 IU/mL. Sustained virologic response was achieved in 96% (95% CI, 94-97%) of patients (Table). Response rates were similar regardless of the presence or absence of cirrhosis (95 versus 96%, respectively). Virologic failure was observed in 18 (2.5%) patients, 5 (0.7%) with on-treatment breakthrough and 13 (1.8%) with post-treatment relapse. Seven patients (1.0%) discontinued treatment due to AEs, 4 of whom subsequently achieved SVR12. The most common AEs were fatigue (41%), headache (33%), nausea (23%), and insomnia (17%). Grade 3+ laboratory abnormalities were infrequent for ALT (0.9%), AST (0.6%), haemoglobin (0.3%), and total bilirubin (2.8%).

Abstract number: P0668

SVR12 by baseline factors, n/N (%)	GT1a with no cirrhosis 3D + RBV for 12 weeks	GT1a with cirrhosis 3D + RBV for 24 weeks	Overall
Overall	569/593 (96)	115/121 (95)	684/714 (96)
Sex Male Female	353/370 (95) 216/223 (97)	84/89 (94) 31/32 (97)	437/459 (95) 247/255 (97)
Treatment-naïve	403/420 (96)	53/56 (95)	456/476 (96)
Prior PegIFN/RBV non-response Relapse Partial response Null response	47/50 (94) 36/36 (100) 83/87 (95)	13/13 (100) 10/10 (100) 39/42 (93)	60/63 (95) 46/46 (100) 122/129 (95)
IL28B genotype CCCTTT	157/163 (96) 323/338 (96) 89/92 (97)	24/25 (96) 72/75 (96) 19/21 (90)	181/188 (96) 395/413 (96) 108/113 (96)

Conclusion: In HCV GT1a-infected patients, the label-recommended 3D regimen with RBV achieved high SVR12 rates, including historically difficult-to-cure subgroups of patients with prior PR null response and/or cirrhosis.

Disclosure of Interest: H. Wedemeyer Financial support for research: Abbott, Bristol-Myers Squibb, MSD, Novartis, Roche, Consultancy: Abbott, AbbVie, Achillion, BMS, Boehringer Ingelheim, Gilead, GSK, ITS, Janssen, Merck, Novartis, Roche, Roche Diagnostics, Siemens, Transgene, P. Pockros Financial support for research: Gilead, AbbVie, Janssen, Bristol-Myers Squibb, Merck, Conatus, Roche Molecular, Consultancy: Gilead, AbbVie, Janssen, Bristol-Myers Squibb, S. Lee Financial support for research: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead, Idenix, Janssen, Merck, Roche, Vertex, Lecture fee(s): Bristol-Myers Squibb, Gilead, Merck, Roche, Vertex, Consultancy: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead, Idenix, Janssen, Merck, Roche, Vertex, E. Gane Consultancy: AbbVie, Gilead, Achillion, Idenix, Novartis, Roche, Merck, Janssen, C. Moreno Financial support for research: Merck, Janssen, Gilead, Novartis, Roche, Lecture fee(s): MSD, Janssen, Gilead, AbbVie, Bristol-Myers Squibb, Consultancy: MSD, Janssen, Gilead, AbbVie, Bristol-Myers Squibb, S. Strasser Lecture fee(s): AbbVie, Janssen, MSD, Bristol-Myers Squibb, Gilead, Roche, Consultancy: AbbVie, Janssen, MSD, Bristol-Myers Squibb, Gilead, Roche, V. De Ledinghen Consultancy: AbbVie, Bristol-Myers Squibb, Gilead, Merck, Janssen, Echosens, A. Maieron Financial support for research: Roche, MSD, Consultancy: MSD, Janssen Therapeutics, AbbVie, Boehringer Ingelheim, Gilead, Bristol-Myers Squibb, Rottapharm-Madaus, W. Xie Shareholder: AbbVie, Conflict with: AbbVie, R. Trinh Shareholder: AbbVie, Conflict with: AbbVie, Y. Luo Shareholder: AbbVie, Conflict with: AbbVie, F. Tatsch Shareholder: AbbVie, Conflict with: AbbVie, V. Rustgi Financial support for research: AbbVie, Gilead, Hyperion, Inovio, Consultancy: AbbVie, Bristol-Myers Squibb, Gilead, Merck

P0669 99.7% SUSTAINED VIROLOGIC RESPONSE RATE IN 369 HCV GENOTYPE 1B-INFECTED PATIENTS TREATED WITH LABEL-RECOMMENDED REGIMEN OF OMBITASVIR/PARITAPREVIR/R AND DASABUVIR WITH OR WITHOUT RIBAVIRIN

J.-F. Dufour¹, H. Wedemeyer², D. E. Bernstein³, M. Colombo⁴, M. Romero-Gomez⁵, N. Reau⁶, R. Trinh⁷, W. Xie⁷, J. V. Enejosa⁷, D. E. Cohen⁷, M. Martinez⁷, I. M. Jacobson⁸

¹University Clinic for Visceral Surgery and Medicine, Inselspital, Bern, Switzerland, ²Medizinische Hochschule Hannover, Hannover, Germany, ³North Shore University Hospital, Manhasset, United States, ⁴Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy, ⁵Hospital Universitario de Valme, Universidad de Sevilla, Sevilla, Spain, ⁶University of Chicago Medical Center, Chicago, ⁷AbbVie Inc., North Chicago, ⁸Weill Cornell Medical College, New York, United States

Contact E-mail Address: marisol.martinez@abbvie.com

Introduction: The 3 direct-acting antiviral (3D) regimen of ombitasvir (an NS5A inhibitor), paritaprevir (an HCV NS3/4A protease inhibitor identified by AbbVie and Enanta, boosted with ritonavir) and dasabuvir (a non-nucleoside NS5B RNA polymerase inhibitor) is approved to treat patients infected with HCV genotype (GT) 1. We report the safety and efficacy of the label-recommended 3D regimen with or without ribavirin (RBV) in treatment-naïve and prior pegIFN/RBV-experienced patients with GT1b infection, with or without cirrhosis, using pooled data from three phase 3 studies.

Aims & Methods: Genotype 1b-infected patients from the PEARL-II, PEARL-III, and TURQUOISE-II studies were included in this post-hoc analysis. Efficacy was assessed by the proportion of patients achieving sustained virologic response (HCV RNA <25 IU/mL) 12 weeks after completion of treatment (SVR12). Per the US Prescribing Information and European SmPC, the label-recommended regimen for GT1b infection is 3D for 12 weeks in non-cirrhotic patients, and 3D + RBV for 12 weeks in patients with cirrhosis. Adverse events (AEs) and laboratory measures are reported for all patients receiving the label-recommended regimen.

Results: Among 369 HCV GT1b-infected patients treated with the label-recommended 3D ± RBV regimen, 50% were male, 37% were treatment-experienced, 18% had cirrhosis, 83% had an IL28B non-CC genotype, and 78% had baseline viral loads ≥800,000 IU/mL. Sustained virologic response was achieved in 368/369 (99.7%; 95% CI, 98.2-99.9%). One patient experienced post-treatment relapse, a 56 year-old white male with cirrhosis who received 3D + RBV. The majority of AEs were mild to moderate in severity, and most common AEs were headache (24%), fatigue (22%), and asthenia (9%). Grade 3 laboratory abnormalities were infrequent for ALT (0.3%), AST (0.3%), and total bilirubin (2.2%). No patient experienced a grade 3 haemoglobin decline and no patient discontinued treatment prematurely due to an AE.

Abstract number: P0669

SVR12 by baseline factors, n/N (%)	GT1b without cirrhosis 3D for 12 weeks	GT1b with cirrhosis 3D + RBV for 12 weeks	Overall
Overall	301/301 (100)	67/68 (98.5)	368/369 (99.7)
Sex Male Female	141/141 (100) 160/160 (100)	44/45 (97.8) 23/23 (100)	185/186 (99.5) 183/183 (100)
Treatment-naïve	210/210 (100)	22/22 (100)	232/232 (100)
Prior PegIFN/RBV non-response Relapse Partial response Null response	33/33 (100) 26/26 (100) 32/32 (100)	14/14 (100) 6/7 (85.7) 25/25 (100)	47/47 (100) 32/33 (97.0) 57/57 (100)
IL28B Genotype CC CT TT	51/51 (100) 197/197 (100) 53/53 (100)	9/10 (90.0) 45/45 (100) 13/13 (100)	60/61 (98.4) 242/242 (100) 66/66 (100)

Conclusion: Patients with HCV GT1b infection treated with the label-recommended 3D regimen, with or without RBV, achieve very high SVR12 rates, including those with historically difficult-to-cure disease characteristics such as prior pegIFN/RBV null response and cirrhosis.

Disclosure of Interest: J.-F. Dufour Lecture fee(s): Bayer, Boehringer-Ingelheim, Novartis, and Roche, Consultancy: Bayer, Bristol-Myers Squibb, Gilead, Janssen Cilag, Jennerex, Merck, Novartis, Roche, H. Wedemeyer Financial support for research: Abbott, Bristol-Myers Squibb, MSD, Novartis, Roche, Lecture fee(s): Abbott, AbbVie, Achillion, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead, GSK, ITS, Janssen, Merck, Novartis, Roche, Roche Diagnostics, Siemens, Transgene, Consultancy: Abbott, AbbVie, Achillion, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead, GSK, ITS, Janssen, Merck, Novartis, Roche, Roche Diagnostics, Siemens, Transgene, D. Bernstein Financial support for research: AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Vertex, Merck, Genentech, Lecture fee(s): AbbVie, Gilead, Janssen, Vertex, Merck, Consultancy: AbbVie, Gilead, Janssen, Vertex, Merck, M. Colombo Financial support for research: Merck, Roche, Bristol-Myers Squibb, Gilead, Lecture fee(s): Tibotec, Roche, Novartis, Bayer, Bristol-Myers Squibb, Gilead, Vertex, Consultancy: AbbVie, Merck, Roche, Novartis, Bayer, Bristol-Myers Squibb, Gilead Sciences, Tibotec, Vertex, Janssen Cilag, Achillion, Lundbeck, Abbott, Boehringer Ingelheim, GSK, GenSpera, M. Romero-Gomez Lecture fee(s): AbbVie, Roche, Gilead, MSD, Janssen, Merz, Bristol-Myers Squibb, Boehringer Ingelheim, GSK, Consultancy: AbbVie, Roche, Gilead, MSD, Janssen, Merz, Bristol-Myers Squibb, Boehringer Ingelheim, GSK, N. Reau Financial support for research: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Merck, Consultancy: AbbVie, Bristol-Myers Squibb, Gilead, Merck, R. Trinh Shareholder: AbbVie, Conflict with: AbbVie, W. Xie Shareholder: AbbVie, Conflict with: AbbVie, J. Enejosa Shareholder: AbbVie, Conflict with: AbbVie, D. Cohen Shareholder: AbbVie, Conflict with: AbbVie, M. Martinez Shareholder: AbbVie, Conflict with: AbbVie, I. Jacobson Financial support for research: AbbVie, Achillion, Bristol-Myers Squibb, Gilead, Janssen, Merck, Lecture fee(s): AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Consultancy: AbbVie, Achillion, Bristol-Myers Squibb, Enanta, Gilead, Janssen, Merck, Roche

P0670 HEPATITIS C VIRUS–ASSOCIATED B-CELL NON-HODGKIN LYMPHOMAS – AN ALTERNATIVE THERAPEUTIC APPROACH?

J. Castela¹, P. Sousa¹, C. Leitão¹, S. Mão de Ferro¹, S. Ferreira¹, M. Cunha¹, M. Silva¹, A. Dias Pereira¹

¹Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal

Contact E-mail Address: joanarocastela@gmail.com

Introduction: The most compelling argument for a causal relationship between hepatitis C virus (HCV) infection with B-cell non-Hodgkin Lymphoma (B-NHL) results from the demonstration of regression of some indolent B-NHL with the eradication of HCV. The role of HCV treatment as a first line therapy remains to be defined, particularly with the availability of new antivirals.

Aims & Methods: Clinical and demographic characterization of population with B-NHL and hepatitis C. Evaluation of eligibility for HCV therapy as the first line treatment for B-NHL.

Retrospective study of patients with B-NHL anti-HCV+, followed in a clinical center for 11 years. The clinical and demographic characteristics were analysed. Eligibility criteria for HCV therapy: indolent lymphomas, unless bulky or symptomatic disease.

Results: Of 2826 patients with B-NHL 37 were anti-HCV+, 17 men, mean age 60 ± 16 years. Viral load determined in 21 patients, detected in 16 (HCV-RNA +).

Fifteen patients had indolent lymphomas (non-classifiable-5, extranodal marginal-2, chronic lymphocytic leukemia-4, lymphoplasmacytic lymphoma-2, follicular lymphoma-2). Eleven were HCV-RNA+. According to the eligibility criteria, one would be excluded for being bulky and the remaining 10 would be candidates for primary therapy of HCV (only 7 eligible for INFpeg and ribavirin: 2 non responders to prior treatment and 1 anemia). No patient was treated for HCV as first-line therapy for lymphoma. 10/15 patients received chemotherapy (CT). Two patients had elevated transaminases during chemotherapy that did not require dose reduction.

Conclusion: Given the low prevalence of HCV infection, the number of patients who could benefit from anti-HCV therapy as primary treatment for B-NHL is reduced. However, given the possibility of regression of indolent lymphomas and the availability of new drugs for HCV with fewer side effects and greater efficiency, this therapy should be offered to eligible patients before chemotherapy.

Disclosure of Interest: None declared

P0671 "EARLY” SUBCLINICAL LEFT VENTRICULAR DISFUNCTION IN HEPATITIS C VIRUS INFECTION

A. Rocco¹, M. Sanduzzi Zamparelli¹, D. Angrisani¹, D. Compare¹, P. Coccoli¹, C. Santoro², M. Galderisi², G. Nardone¹

¹Department of Clinical Medicine and Surgery, Gastroenterology, ²Hypertension Research Center and Department of Medical Translational Sciences, Federico II University, Naples, Italy

Contact E-mail Address: marcosanduzzizamparelli@yahoo.it

Introduction: Hepatitis C virus (HCV) infection has been associated with several extrahepatic manifestations in a variety of tissues and organs, including the myocardium. Reduced myocardial perfusion or increased pro-B-type natriuretic peptide (NT-proBNP) have been described in HCV-infected individuals but, until now, no study clearly demonstrated the occurrence of myocardial dysfunction in the early stages of HCV-related liver diseases

Aims & Methods: Aim was to evaluate the impact of HCV infection on ventricular geometry and function by a standard 2D and 3D echocardiography.

50 out of 125 consecutive genotipe 1 HCV infected patients with histologically proved HCV-related chronic hepatitis and 30 Healthy Controls (HCs), comparable for age and gender prevalence were enrolled in the study. Laboratory tests, abdominal utrasonography, liver biopsy or FibroScan and ecocardiography were performed in all the patients. The echocardiography protocol consisted of: standard echo Doppler plus LV volumetric and systolic function analysis through 3D echocardiography. Left ventricular systolic function thorough 3D echo was evaluated by Speackle tracking echocardiography (STE) derived global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS) and global radial strain (GRS).

Results: Overall we enrolled 28 males and 22 females with HCV (genotype 1) related chronic liver disease. Mean age was 59.8 ± 6.9yrs. Age, gender distribution, body mass index, heart rate and blood pressure did not significantly differ between patients and controls. In HCV infected subjects standard 2D echocardiography point out a transmitral E/A ratio marginally lower (0.84 ± 0.2) compared to HC (1.01 ± 0.3) (p=0.04). Moreover, more detail 3D STE showed in 38 (76%) of the cases a subclinical alteration of LV function, documented by lower GCS (HCV=-15.3 ± 2.2%, HC=-17.6 ± 3.9%, p=0.02), GAS (-25.2 ± 2.6%, HC -29.9 ± 5.2%, p=0.03), and GRS (37.6 ± 4.6% vs 44.9 ± 12%, p=0.04) whereas HCV-releated changes of GLS were not significant. Interestingly, myocardial impairment was independent of viral load and staging of liver biopsy.

Conclusion: HCV infected patients show a subclinical myocardial dysfunction independently of viral load and liver fibrosis; circumferential fibers of the left ventricular mid wall are primarily involved in LV subclinical dysfunction.

Disclosure of Interest: None declared

P0672 USEFULNESS OF LIVER FIBROSIS ASSESSMENT IN PATIENTS WITH CHRONIC HEPATITIS C (CHC) USING GLYCO-ISOMER OF SERUM MAC-2-BINDING PROTEIN

M. Hamano¹, M. Naito¹, Y. Kawasaki¹, T. Tokuda¹, M. Matsushita¹, Y. Sato¹, A. Sakai¹, A. Kusakabe¹, C. Hibino¹, H. Saiki¹, M. Kato¹, Y. Tokuda¹, A. Ishimi¹, T. Kawai¹, M. Chiba¹, K. Maeda¹, K. Yamamoto¹, T. Ito¹

¹Japan Community Healthcare Organization Osaka Hospital, Osaka, Japan

Contact E-mail Address: mina-hamano@okn.gr.jp

Introduction: The degree of liver fibrosis is a major issue for making decision of therapeutic strategies on chronic liver diseases. Recently glyco-isomer of serum Mac-2-binding protein (M2BPGi) could be supposed to be a novel and useful biomarker to assess liver fibrosis. However little is known about its usefulness for diagnosis of CHC patients.

Aims & Methods: In this study, we were trying to reveal the significance of serum M2BPGi for assessment of liver fibrosis. One hundred twenty seven CHC patients (male/female=67/60, mean age 58 y.o.) scheduled for the anti-viral therapy were enrolled. Liver biopsies were undertaken in all of the patients. We evaluated the relation between liver fibrotic degrees and the serum levels of M2BPGi, and the correlation between the serum levels of M2BPGi and examined liver function tests, i.e. T-Bil, AST, ALT, GGT, platelet, AFP, γ-globulin and hyaluronic acid (HA). Additionally we evaluated the ability of M2BPGi by Receiver Operating Characteristic (ROC) analysis compared with the serum levels of HA and Fib4 index.

Results: The patients were classified into two groups according to liver fibrosis stage, F0 (n=34) and F1/2 (n=93). The serum levels of M2BPGi were significantly higher in F1/2 group (median=1.73C.O.I.) than in F0 group (median=0.85C.O.I.), (p<.0001). Among the other serum liver tests, the levels of serum HA were strongly related with liver fibrosis stage (F0=23.0ng/ml vs F1/2=93.5ng/ml, p<.0001), and the serum levels of AST (F0=32IU/L vs F1/2=50IU/L, p<.0005), ALT (F0=36IU/L vs F1/2=59IU/L, p<.01), platelet (F0=21.0 × 10⁴/μl vs F1/2=16.9 × 10⁴/μl, p<.001) and γ-globulin (F0=18.6% vs F1/2=21.1%, p<.001) also indicated significant difference between the two groups. The serum levels of M2PBGi showed the positive correlation with the serum levels of AST (R=0.32), ALT (R=0.26), GGT (R=0.29), γ-globulin (R=0.38) and HA (R=0.70), and the negative correlation with the serum levels of platelet (R=-0.28), respectively. ROC analysis showed that both serum HA (AUC=0.830) and the Fib4 index (AUC=0.809) were the most useful determinants of liver fibrosis comparing between the two groups. The serum levels of M2BPGi (AUC=0.759) showed the possible indicator for liver fibrosis staging as well.

Conclusion: In this study, we could demonstrate that the serum M2BPGi was a potentially significant biomarker for liver fibrosis, even in minimal or mild liver fibrosis. The serum M2BPGi could be one of the most useful tools for assessment of liver fibrosis in CHC patients.

Disclosure of Interest: None declared

P0673 RESPONSE TO HEPATITIS B VACCINE IN CHRONIC HEPATITIS C EGYPTIAN PATIENTS

E. M. Said¹, M. A. Metwally¹, D. M. Abd El Hassib², R. M. Elsawi³, M. M. E. Atta¹

¹Hepatology, Gastroenterology, and Infectious Diseases, ²Clinical and Chemical pathology, ³Pathology, Benha University, Benha, Egypt

Contact E-mail Address: mohamed.metwally@fmed.bu.edu.eg

Introduction: Egypt is cursed with the highest worldwide prevalence of chronic hepatitis C (CHC). Patients with CHC are advised to be vaccinated against hepatitis B virus (HBV) infection. Response to vaccination and risk factors for weak response are not clearly identified.

Aims & Methods

Aim: To assess response to hepatitis B vaccination in CHC patients and identify predictors of weak response.

Patients and methods: This prospective study included 112 consecutive adult, treatment- naive patients with CHC (cases group) and 54 non HCV subjects (control group). Demographic and laboratory variables including HCV-viral load and antischistosomal antibody beside histopathological examination were all collected. Three doses (0, 1 & 6 months) of HBV-vaccine (Euvax B, LG Life Sciences, Korea) were given and hepatitis B surface antibody (HBs-Ab) titre was evaluated 1.5 - 2 months after the 3rd dose.

Results: Out of 112 patients with CHC, 5 (4.5%) had HBs Ab titre less than 10 IU, 20 (17.9%) had less than 100 IU, and 50 (44.6%) had more than 1000 IU. In comparison, out of 54 controls, one (1.9%) had less than 10 IU, 2 (3.8%) had less than 100 IU, and 41 (75.9%) had more than 1000 (P= 0.001). CHC patients had highly significant lower mean antibody titre than controls (P < 0.001). In univariate regression analysis, HBs Ab titre was negatively associated with age (P< 0.001), ALT (P=0.03), AST (P=0.03), FIB4 score (P=0.008), and antischistosomal antibody titre (P= 0.007) and positively associated with platelet count (P=0.01). There was no association with gender, body mass index, viral load or other variables (including METAVIR grade or stage). Multivariate regression analysis in CHC patients showed that age (P= 0.02) and antischistosomal antibody titre (P= 0.04) were the independent predictors for HBs Ab titre response.

Conclusion: CHC patients have a significantly weak response to HBV-vaccine, particularly those with older age and schistosomiasis.

Disclosure of Interest: None declared

P0674 DIFFERENT SERUM FIBROSIS BIOMARKERS AS MONITORING TOOLS FOR DETECTING FIBROSIS REGRESSION IN TREATED HCV PATIENTS

M. Alboraie¹, M. El Kassas², A. Sweedy³, M. Nour⁴, on behalf of Egyptian Liver Fibrosis Study Group

¹Department of Internal Medicine, Al-Azhar University, ²Department of Endemic Medicine and Hepatology, Helwan University, Cairo, ³Damietta Cardiology and Gastroenterology Center, Damietta, Egypt, ⁴Faculty of Public Health & Health Informatics, Umm Al-Qura University, Makkah, Saudi Arabia

Contact E-mail Address: m.alboraie@gmail.com

Introduction: Treating chronic hepatitis C (CHC) is associated with improving long-term outcomes and health-related quality of life. Monitoring fibrosis regression in response to treatment is important to identify patients with residual cirrhosis after CHC cure as they need long-term surveillance for hepatocellular carcinoma (HCC). Due to limitations of repeating liver biopsy after treatment; surrogate biomarkers can be an alternative to monitor fibrosis regression and to identifying patients with residual cirrhosis.

Aims & Methods: We aimed at monitoring regression of fibrosis in a group of CHC patients in response to treatment by calculating six different panels (APRI, FIB-4, PLASA, FRT, Fibro-alpha and BRC) used as non-invasive markers of hepatic fibrosis. Data of 363 CHC patients (140 males) were retrospectively analyzed. Data included pretreatment and post treatment laboratory parameters according to the national guidelines for treating CHC in Egypt (2007-2014). Patients were classified into 4 groups according to treatment response; patients who had sustained virologic response (group 1; n =90), relapsers after treatment (group 2; n =65), patients who had breakthrough during treatment (group 3; n =12) and null responders (group 4; n =71) in addition to a control groups (group 5; n = 125) of CHC patients whom were in eligible or refusing to receive standard of care treatment. All treated patients received pegylated interferon and ribavirn combination. APRI, FIB-4, PLASA, FRT, Fibro-alpha and BRC were calculated at weeks 0 and 72 for all groups and correlated to fibrosis stage by METAVIR and to treatment outcome in different groups.

Results: APRI, FIB-4, PLASA, FRT, Fibro-alpha and BRC could predict significant hepatic fibrosis (≥F2 METAVIR), advanced hepatic fibrosis (≥F3 METAVIR) and cirrhosis (F4 METAVIR) accurately. All panels showed significant decrease of their values in group 1 (sustained virologic response) in response to treatment. On the contrary; APRI, PLASA, FRT and BRC showed significant increase of their values in the control group (table 1). FIB-4 and Fibro-alpha had increase in their values in the control group but this was not significant. There were no other significant changes in the values of the studied panels in other treatment groups.

Abstract number: P0674 Table 1.

Week zero and week 72 values of different biomarker panels among group 1 (SVR) and groups 5 (control) patients.

Biomarker panels	Week zero(95 % CI)	Week 72(95 % CI)	P-value
APRI (mean ±SD)- SVR- Control	1.14±1.160.9 ±0.92	0.44± 0.41.14±1.27	<0.0010.004
FIB-4 (mean ±SD)- SVR- Control	2.13±1.462.52±2.25	1.52±0.892.86± 2.5	<0.0010.058*
PLASA(mean ±SD)- SVR- Control	0.53±1.180.53±1.04	-0.29±0.630.71±1.19	<0.0010.008
FRT(mean ±SD)- SVR- Control	10.0± 3.511.8± 6.5	8.4 ±1.913.6±10.1	<0.0010.034
Fibro-alpha(mean ±SD) - SVR- Control	1.33±0.131.38±0.25	1.36±0.131.42± 0.3	<0.0010.057*
BRC(mean ±SD)- SVR- Control	7.5 ±3.110.0± 6.8	6.9 ±2.511.7± 9.9	0.0160.038

*Non -significant difference. SVR: Sustained virologic response

Conclusion: All of the studied biomarker panels for liver fibrosis assessment were useful in monitoring regression of fibrosis in treated CHC patients and most of them were useful in monitoring progression of fibrosis in untreated patients.

Disclosure of Interest: None declared

P0675 31PHOSPHORUS MAGNETIC RESONANCE SPECTROSCOPY OF THE LIVER IDENTIFIES INFLAMMATION IN AUTOIMMUNE HEPATITIS

L. Puustinen¹², A. Hakkarainen³, U. Nieminen⁴, R. Kivisaari³, N. Lundbom³, P. Arkkila¹

¹Clinic of Gastroenterology, Helsinki University Hospital, ²Helsinki University, ³Department of Radiology, HUS Helsinki Medical Imaging Center, Helsinki University Hospital, ⁴Clinic of Gastroenterology, Helsinki University Central Hospital, Helsinki, Finland

Contact E-mail Address: lauri.puustinen@helsinki.fi

Introduction: Remission in autoimmune hepatitis (AIH) is defined as normal aminotransferases and normal IgG levels and no or only slight inflammation in liver biopsy. Transient elastography (TE) has become a useful method in measuring fibrosis, but biopsy has remained the gold standard in revealing both fibrosis and inflammation of the liver. Liver biopsy is invasive, costly, and subject to complications and sampling variability. The information about inflammation in addition to fibrosis is important in clinical decision of continuing or stopping the treatment. Thus, a non-invasive and accurate test for diagnosis of inflammation would be of great value and we have tested ³¹phosphorus magnetic resonance spectroscopy (³¹P MRS) in this setting.

Aims & Methods: Twelve consecutive AIH patients (mean age 42.8 years, eleven women) who underwent liver biopsy for disease staging, were evaluated with TE and ³¹P MRS. Inflammation and fibrosis in liver biopsy were categorized according to Metavir score. ³¹P-MRS of liver was performed on a 3 Tesla clinical imager (Philips, Achieva). A 125-216 cm3 voxel was placed in the center of right liver lobe and proton decoupled 31P-MR spectra were obtained using image selective in vivo spectroscopy (ISIS) with TR of 6000 ms and 128 acquisitions. 31P-MRS data was collected with a circular 31P transmit receive loop coil. Body coil was used for obtaining localizer images and for proton decoupling.

Phosphoenolpuryvate (PEP)/phosphatidylcholine (PtdC), phosphoethanolamine (PE), glyserophosphoethanolamine (GPE), total phosphomonoester level (PME), total phosphodiester level (PDE), and PE/PC, PE/GPE, and PC/(PME + PDE) ratios were compared to Metavir grade and stage, stiffness in TE and alanine aminotransferase (ALT), aspartate aminotransferase (AST), immunoglobulin-G (IgG), alkaline phosphatase (ALP), thrombolastin time (TT), and albumin (Alb). Spearman's and Pearson correlations were used to assess statistical relationships. p<.05 was considered statistically significant.

Results: PEP/PtdC correlated with inflammation grade (r=.663, p=.019) and ALP (r=.598, p=.040). PE/PC (r=.764, p=.006), PE/GPE (r=.618, p=.043), and PC/(PME + PDE) (r=-.636, p=.035) correlated with inflammation, as measured with IgG (r=.764, p=.006; r=.618, p=.043; and r=-.636, p=.035), respectively. There was no correlation between phosphorus metabolites and TE, histological fibrosis and aminotransferase levels.

The histological inflammation correlated with ALT and AST (r=.800, p=.002 and r=.673, p=.023 respectively) and IgG (r=.604, p=.049). TE did not correlate with phosphorus metabolites, liver histology, or laboratory parameters.

Conclusion: ³¹P MRS measures inflammatory activity in AIH patients. TE and MRS were not effective in fibrosis quantification.

Disclosure of Interest: None declared

P0676 THE ROLE OF POINT SHEAR WAVE ELASTOGRAPHY TECHNIQUE (ELASTPQ) IN THE NON-INVASIVE ASSESSEMENT OF LIVER FIBROSIS IN VARIOUS LIVER DISEASES

M. Garcovich¹, M. Pompili¹, E. Di Stasio¹, L. Riccardi¹, M. E. Ainora¹, A. Grieco¹, G. L. Rapaccini¹, M. Siciliano¹, A. Gasbarrini¹, M. A. Zocco¹

¹Catholic University of Sacred Heart, Rome, Italy

Introduction: Point shear wave elastography (PSWE) is a novel non-invasive technique that assesses liver fibrosis by measuring liver stiffness (in kPa) with few studies published so far. The aim of this study was to determine the accuracy and the feasibility for the assessment of liver stiffness in comparison to the fibrosis stage in patients undergoing liver biopsy (LB) for various etiologies.

Aims & Methods: Consecutive patients scheduled for LB were studied by using the iU22 Philips ultrasound system with ElastPQ technique. The correlations between laboratory findings, liver stiffness and the Metavir score were analyzed using Spearman correlation and ROC curve analyses were performed to calculate AUC for F ≥ 2, F ≥ 3 and F=4.

Results: We enrolled 217 patients (140/77 males/females) who underwent LB for viral or non-viral chronic hepatitis (HCV 44%; NASH 21%; AIH/PBC 18%; other 17%). Liver stiffness measurements performed on the right lobe were reliable in all cases but two (due to morbid obesity and narrow intercostal spaces). After univariate and multiple regression analysis PSWE showed a strong correlation with the fibrosis stage; no significant correlation was found with the degree of necroinflammation or steatosis. Mean kPa values in the whole cohort were 4.01 (range 2.30–5.69) for F0, 4.89 (range 2.62-9.68) for F1, 8.00 (2.81-20.79) for F2, 10.98 (3.88-21.44) for F3 and 18.61 (9.51-31.34) for F4 in the right lobe. AUROCs were 0.90 (±0.02), 0.91 (±0.02) and 0.97 (±0.01), when comparing F0-F1 vs F2-F4, F0-F2 vs F3-F4 and F0-3 vs F4, respectively. The optimal cut-off values for different levels of fibrosis were 6.03, 7,63 and 9.47 kPa for F ≥ 2, F ≥ 3 and F4, respectively. When analyzing PSWE values according to different etiologies, AUROCs were 0.85 (±0.04), 0.97 (±0.29) and 0.94 (±0.03) for F ≥ 2; 0.88 (±0.04), 0.95 (±0.03) and 0.95 (±0.03) for F ≥ 3; 0.98 (±0.01), 0.99 (±0.01) and 0.99 (±0.01) for F4 in HCV, NASH and AIH/PBC patients, respectively.

Conclusion: PSWE with ElastPQ appears to be a useful tool for non-invasive evaluation of fibrosis not only in patients with viral chronic hepatitis, but also for patients with different liver diseases. In order to validate such a non-invasive technique these findings need to be confirmed in larger studies.

Disclosure of Interest: None declared

P0677 PHARMACOKINETICS, RADIATION DOSIMETRY AND TOXICOLOGY STUDIES OF 111IN-DTPA HEXA-LACTOSIDE IN NORMAL MICE

M. H. Wang¹, C.-Y. Chien¹, H.-M. Yu¹, W.-J. Lin¹

¹Isotopes, Institute of Nuclear Energy Research, Taoyuan, Taiwan, Province of China

Contact E-mail Address: mhwang@iner.gov.tw

Introduction: Asialoglycoprotein receoptors residing on hepatocyte membrane has been known to specifically bind with GalNAc or Gal terminal glycoligands. ¹¹¹ In-DTPA hexa-lactoside with Gal termini were developed as a biomarker for liver reserve measurement. In previous study, 111In-DTPA hexa-lactoside has been validated as a specific imaging biomarker for asialoglycoprotein receptors on hepatocyte membrane.

Aims & Methods: To advance ¹¹¹ In-DTPA hexa-lactoside to first-in-human trial, pharmacokinetics, radiation dosimetry and toxicology studies of ¹¹¹In-DTPA hexa-lactoside in normal mice were performed to meet the requirements of regulatory approval for Investigational new drug (IND). The pharmacokinetic parameters were calculated according to the radioactivity elimination curve with the assistance of PK-Solver 2.0 software. The radiation exposure dose was measured by the OLINDA/EXM program on the basis of residence time of radioactivity in each organ, radiation energy of radionuclide, radionuclide type and tissue-weighting factor of International Commission on Radiological Protection (ICRP). A 14-day GLP extended acute toxicity was evaluated in male Sprague-Dawley (SD) rats via single intravenous injection administration of DTPA-hexa-lactoside.

Results: ¹¹¹In-DTPA hexa-lactoside exhibited biexponential elimination from the blood in normal mice following tail vein i. v. administration. The distribution half-life (α-phase) was 0.42 min. The elimination phase half-life (β-phase) was 11.46 min. The highest concentration of radioactivity was mostly found in liver (up to 55.48 ± 8.19 %ID/g) within 30min p. i. The mean residence time in blood and liver were 8.22 min and 22.44 h, respectively. The estimated total body dose was 2.86E-05 mSv/MBq which corresponds to a whole body dose of 1.0582 mSv per 1 mCi administered dose, i.e. 1/10 exposure dose of Chest X ray. No significant differences were observed for hematology and serum biochemistry parameters. The physiological functions of all animals were remaining normal during the study period. All parameters of clinical pathology were within the range of historical data.

Conclusion: Our data indicates ¹¹¹In-DTPA hexa-lactoside is suitable for advancement to a first-in-humans clinical trial.

Disclosure of Interest: None declared

P0678 NEAR INFRARED FLUORESCENCE DYE LABELED MULTIVALENT DEOXYGLUCOSE AS AN IMAGING AGENT FOR DETECTION OF LIVER CANCER

M. H. Wang¹, Y.-F. Chiang¹, R.-Y. Chen¹, C.-Y. Chien¹, W.-J. Lin¹

¹Isotopes, Institute of Nuclear Energy Research, Taoyuan, Taiwan, Province of China

Contact E-mail Address: mhwang@iner.gov.tw

Introduction: According to the statistics of American Cancer Society, one-fourth quarter of deaths are due to cancer in US. There is still a lot of unmet need in medical technology, especially in early diagnosis and therapeutic monitoring of liver cancer. Although F-18 FLT is very good as cell proliferation agent, we did not see good image in the orthotopic SK-HEP-1 bearing hepatoma mice in our preliminary experiment because the high unwanted interference in the abdomen.

Aims & Methods: In this study, we develop a fluorescent imaging biomarker with multivalent deoxyglucoside to see its feasibility for hepatoma targeting. Trivalent deoxyglucoside was made by a nitrile-triacetic acid linking three aminohexanoyl-deoxyglucoside. Hexa-deoxyglucoside was synthesized by dimerization of trivalent deoxyglucoside via amide bond formation with cy dye. The fluorescence imaging was performed in the Xtreme system. Biodistribution study was studied by imaging individual organ in vitro after sacrifice mice by cervical dislocation.

Results: Both Cy dye and cy dye-hexa-deoxyglucose performed accumulation in the tumor site bearing SK-HEP-1; however, cy dye-hexa-deoxyglucoside showed more specific for hepatoma targeting than cy dye only. The biodistribution imaging indicated there is highest absorption in the hepatoma region than normal region. Kidney was the next high accumulation organ, which revealed its water solubility property. There is low absorption in the other major organs such as heart, normal liver region, spleen and lung etc.

Conclusion: Our preliminary data indicated the cy dye-hexa-deoxyglucoside has hepatoma targeting property and was possible a good predictor for surgery-guided therapy.

Disclosure of Interest: None declared

P0679 PERCUTANEOUS SCLEROTHERAPY USING COMBINED ETHANOL AND TETRACYCLINE FOR TREATING SYMPTOMATIC SIMPLE HEPATIC CYSTS

H. Elalfy¹, T. Besheer¹, K. Farid¹, M. Elegezy¹, W. Elkashef², A. M. Elkhalek³, A. Elhawary¹, M. El-Bendary¹

¹Tropical Medicine, ²Pathology Department, ³Radiology, Mansoura University, Mansoura, Egypt

Contact E-mail Address: doc_mohamed_hashash@yahoo.com

Introduction: Simple hepatic cysts are benign congenital cysts with a prevalence of 2.5-4.25%. very few cases of simple hepatic cysts need treatment. Ethanol is the most commonly used agent for percutaneous sclerotherapy. Pain is a common complication with ethanol sclerotherapy and is related to the injected amount.

Aims & Methods: our aim is to evaluate the safety and efficacy of the combination of tetracycline and ethanol for percutaneous sclerotherapy of simple hepatic cysts. A total of 34 adult patients with symptomatic simple hepatic cyst underwent clinical evaluation, laboratory evaluation, radiological evaluation and diagnostic cyst aspiration. They were divided into 2 groups. The first group was treated by percutaneous ethanol sclerotherapy and the second was treated by combined ethanol and tetracycline sclerotherapy.

Results: Combined ethanol and tetracycline sclerotherapy was associated with fewer sessions than ethanol sclerotherapy(P= ≤0.001) and higher rate of sustained cyst size reduction on follow up (P= ≤0.001). There was no significant difference between the two procedures regarding the complications. Hepatitis C virus infected patients and those with hepatic steatosis had non-significant changes in the serum transaminases with the two procedures.

Conclusion: percutaneous sclerotherapy of simple hepatic cysts using tetracycline and ethanol is more effective than ethanol sclerotherapy.

Disclosure of Interest: None declared

P0680 FACTORS THAT INFLUENCE THE CONTROLLED ATTENUATION PARAMETER (CAP) VALUE IN CHRONIC LIVER DISEASE PATIENTS

P. Andrade¹, E. Rodrigues-Pinto¹, R. Gaspar¹, S. Lopes¹, G. Macedo¹

¹Gastroenterology Department, Centro Hospitalar São João, Porto, Portugal

Contact E-mail Address: anapatriciarandrade@gmail.com

Introduction: Controlled Attenuation Parameter (CAP) measured by transient elastography has been suggested as a non-invasive method for detection and quantification of hepatic steatosis. Factors that influence the assessment of steatosis by CAP are not well established.

Aims & Methods: To evaluate the factors influencing the CAP value in a group of patients with chronic liver disease (CLD). This study included CLD patients who underwent CAP measurement using the M probe of Fibroscan (Echosens, Paris, France).

Results: We included 159 patients (61% men, mean age 47.9 ± 12.9 years). CLD aetiology was non-alcoholic fatty liver disease (34.8%), viruses (28.3%), autoimmune hepatitis (10.7%), alcohol (8.7%) and others (17.5%). CAP value was related to the degree of steatosis in liver histology (p <0.001) and ultrasound (p <0.001). The value of CAP was significantly higher in patients with hypertension (267.5 vs. 234.8 dB/m, p=0.007), dyslipidaemia (273.5 vs. 212.1 dB/m, p < 0.001), type 2 diabetes mellitus (280.9 vs. 234.8 dB/m, p=0.001), body mass index (BMI) > 25 Kg/m² (277.8 vs 213.0 dB/m, p < 0.001) and non-alcoholic fatty liver (290.8 vs 212.6 dB/m, p < 0.001). In the multivariate analysis, BMI > 25 Kg/m² (OR 48.4, 95% CI: 23.78 - 72.95, p <0.001), serum cholesterol [OR 3.803, 95% CI: 2203-13889, p <0.008) and non-alcoholic fatty liver aetiology (OR 40.8, 95% CI: 15.01 - 66.66, p = 0.002) were independently associated with higher CAP values; CAP was not influenced by the degree of fibrosis (p = 0.794) or inflammatory activity (p=0.893) in histology, triglycerides (p = 0.104), glucose (p=0.871), ALT (p=0.817) or AST (p=0.372).

Conclusion: CAP mean value increases according to the degree of steatosis in histology and ultrassonography. NAFLD, BMI > 25 kg/m² and serum cholesterol were independently associated with higher values of CAP. The degree of fibrosis and inflammatory activity in histology, triglycerides, blood glucose and transaminases did not influence the value of CAP.

Disclosure of Interest: None declared

P0681 ALTERATIONS IN THE PORTAL VENOUS SYSTEM IN IDIOPATHIC NON-CIRRHOTIC PORTAL HYPERTENSION: A PROSPECTIVE LONG-TERM FOLLOW-UP STUDY

A. Krishnan¹

¹Department of Clinical Medicine, Windsor University School of Medicine, St.Kitts and Nevis, Saint Kitts and Nevis

Contact E-mail Address: dr.arunkumarpillai@gmail.com

Introduction: Idiopathic Non-Cirrhotic Portal Hypertension (INCPH) is a group of diseases that are characterized by an increase in portal pressure, due to intrahepatic or prehepatic lesions, in the absence of cirrhosis of the liver. INCPH includes Extra Hepatic Portal Vein Obstruction (EHPVO) and Non-Cirrhotic Portal Fibrosis (NCPF). The natural history of INCPH is still not clear.

Aims & Methods: Aim of the present was to determine prospectively the changes in the portal venous system in patients with NCPH. Patients with a diagnosis of NCPF and EHPVO registered since 2001 were serially followed at an yearly interval for changes in liver size, its echotexture, and in the intra and extrahepatic portal venous system. Baseline demographic details, LFT, and co-morbid illness including virological profile were noted. Patients with co-morbid illness and those with known etiology of cirrhosis were excluded from the study.

Results: There were 34 patients with NCPF (M: F 1:1.8) and 30 patients with EHPVO (M: F ratio 1.6:1). The mean age was 24.9 yrs and 41.2 yrs respectively. During follow up, 20 out of 34 and 16 out of 30 patients with NCPF and EHPVO respectively had no progression of disease. 14 patients with NCPF progressed to cirrhosis over a mean period of 5.21 years. Eight patients developed ascites and required diuretics. 14 patients with EHPVO progressed to NCPF over the mean period of 8.6 years, 12 patients further progressed to cirrhosis over a mean period of 5.1 years. Overall 40% of patients with EHPVO progressed to cirrhosis over a mean period of 13.7 years.

Conclusion: INCPH is a spectrum wherein EHPVO progresses to NCPF and further to cirrhosis over a period of 13.7 years at least in a proportion of patients. So our report clearly emphasizes that INCPH is a spectrum of disease, so this patients should monitored periodically to observer the changes in the portal venous system.

Disclosure of Interest: None declared

P0682 NON-ALCOHOLIC FATTY LIVER DISEASE RISK FACTORS ASSESSMENT AMONG THE GENERAL PRACTITIONER’S AND GASTROENTEROLOGIST’S PATIENTS FLOW

V. T. Ivashkin¹, O. M. Drapkina¹, I. V. Maev², A. S. Troukhmanov¹, U. V. Zimovina³, L. K. Palgova⁴, D. V. Blinov³, E. N. Shirokova¹, V. V. Tsukanov⁵

¹First Moscow State Medical University, ²MSMSU, ³Sanofi, Moscow, ⁴NWSMU, St Petersburg, ⁵Institute of Medical Problems of the North SB RAS, Krasnoyarsk, Russian Federation

Contact E-mail Address: blinov2010@gmail.com

Introduction: Prevalence of suspected Non-alcoholic fatty liver disease (NAFLD) has more than doubled over the past 20 years and currently affects nearly 11% of adolescents and one-half of obese males. In Russia prevalence of NAFLD is increasing from 26,1 to 37,3% during last 7 years. The rapid increase among those obese, independent of body mass index, suggests that other modifiable risk factors have influenced this trend. For a better understanding of the disease etiology and its correlations with risk factors it is necessary to conduct epidemiological studies in Russia. This study was funded and managed by Sanofi Russia.

Aims & Methods

Objective: To evaluate the hierarchy of risk factors of NAFLD in general and within the every age subgroups in GP’s and gastroenterologist’s patient flow.

Materials and methods: A total of 50145 patients meeting the inclusion/exclusion criteria in 16 Russian cities were enrolled in the Program. The investigators were 1031 qualified doctors (GPs \ therapists \ gastroenterologists \ pediatricians), providing outpatient care for the population. The epidemiological data were obtained, recorded during two routine patient visits to investigating centers.

Results: The patients with Non-cirrhotic non-alcoholic fatty liver disease (NANCFLD) had significant elevated weight, BMI and WC in both gender groups and in total. Among the adult population with NANCFLD, it is important to note a higher and significant value of glucose, insulin, total cholesterol, TG, and HDL cholesterol when compared with participants who had normal liver data. Additionally, patients with NANCFLD resulted in major and significant value of AST, ALT and GGT compared with patients without liver diseases.The more frequent risk factors for females with NANCFLD were: abdominal obesity, BMI ≥ 27kg/m2, menopause, hypertension and metabolic syndrome. The prevalence of reduced High Density Lipoprotein within NANCFLD female patients was 58,0%. The more frequent risk factors for males with NANCFLD were: BMI ≥ 27kg/m2, abdominal obesity, hypertension, hypertriglyceridemia and metabolic syndrome. The prevalence of reduced High Density Lipoprotein within NANCFLD male patients was 40,2%. The main 4 risk factors for NAFLD in males and females were the same and were ranged by odds ratio values as the following: hypertriglyceridemia, metabolic syndrome, BMI ≥ 27kg/m2, abdominal obesity.

Conclusion: NAFLD is closely associated with hypertriglyceridemia, metabolic syndrome, BMI ≥ 27kg/m2, abdominal obesity. It has been confirmed the hypothesis that for each studied risk factor the proportion of patients with NANCFLD is higher than the proportion of patients with the same risk factor in the population without liver diseases.

Disclosure of Interest: None declared

P0683 XRCC1RS1799782, RS25487, RS25489 AND HOGGR1052133 POLYMORPHISM ARE SUSCEPTIBILITY TO EXTRAHEPATIC CHOLANGIOCARCINOMA: A POPULATION-BASED CASE–CONTROL STUDY IN A MEXICAN POPULATION

A. Guitron¹, F. K. Segura-Lopez², J. Torres³, F. Lopez-Marquez⁴, F. Aviles-Jimenez³, H. Valdez-Salazar³, S. Leon-Carballo⁵, L. Guerrero-Perez⁶, J. Garcia-Correa⁷, A. Hernandez-Guerrero⁸, G. Alfaro-Fattel⁹, F. Canzian¹⁰

¹Gastrointestinal Endoscopy, ²Surgery Deprtment, Mexican Institute of Social Security, Torreon, ³Infectious Diseases Research Unity, Mexican Institute of Social Security, Mexico, DF, ⁴Molecular Immunobiology Department, Autonomous University of Coahuila, Torreon, ⁵Gastrointestinal Endoscopy, ISSSTECH, Tuxtla Gutierrez, Chiapas, ⁶Gastrointestinal Endoscopy, Mexican Institute of Social Security, Juarez, Chihuahua, ⁷Gastrointestinal Endoscopy, Mexican Institute of Social Security, Guadalajara, Jalisco, ⁸Gastrointestinal Endoscopy, National Cancer Institute, Mexico, DF, ⁹Gastrointestinal Endoscopy, Mexican Institute of Social Security, Oncology Hospital, Mexico, ¹⁰Genetic Epidemiology Department., DKFZ German Cancer Research Center, Heidelberg, Germany

Contact E-mail Address: aguitron@prodigy.net.mx

Introduction: Up to 90% of patients with extrahepatic cholangiocarcinoma (ECC) have no identifiable risk factors; genetic background (genes programmed to halt proliferation in damaged cells, involved in DNA repair), geographical and environmental factors are considered to play a role in carcinogenesis.

Aims & Methods: The aim was to establish if XRCC1rs1799782, rs25487, rs25489 and hOGG1rs1052133 SNP are susceptibility to ECC. Multicenter, case-control study performed in Mexico between May 2011- December 2013, included adults diagnosed with ECC (cases), benign pathology of the bile duct and asymptomatic patients (controls) matched by sex, age (± 5 years) and place of residence. Genomic DNA was extracted from peripheral blood using QIAamp DNA, quantified using the PicoGreen kit, and stored at -20º C. All SNPs were done with 10 ng genomic DNA in 384-well plates, using TaqMan technologie. The order of DNAs from cases and controls was randomized, for quality control duplicates 10% of the samples were done, PCR reactions were performed using a Hydrocycler instrument and the GeneAmpVR PCR System, PCR plates were read on a ViiA7 real time instrument, the ViiA7 RUO Software, version 1.2.2 was used to determine the genotypes. Hardy-Weinberg equilibrium was tested; logistic regression analyses were used for association between genetic polymorphisms and ECC. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated for each genotype under a codominant, dominant, recessive and additive inheritance model.

Results: Included 391 Mexican patients, 98 EEC: 63 common bile duct, 9 gallbladder and 26 of Vater´s papilla. Mean age of cases (62.2 ± 14.36), 40 men, 58 women. Controls; 92 benign biliary pathology (C1) and 201 asymptomatic blood donors (C2). XRCC1rs1799782_AG, rs25489_CT and hOGG1rs1052133_CG SNP no showed significant differences among groups. rs25487_CT was present in 18.36% of cases (18/98), 38.89 % of C1 (35/90), p= 0.0031, OR= 0.35 (0.17-0.72) and 34% of C2 (69/199), p= 0.056, OR=0.42 (0.23-0.79). XRCC1rs1799782 genotype A/A was observed in 7.94% of choledochal cancer (5/63) vs 1.54% of C2 (2/130) p=0.0385 OR=5.52 (0.91-42.4), genotype A/G was present in 88.89% of gallbladder cancer (8/9) vs 27.77% (5/18) of C2, p=0.0039 OR=20.80 (1.70-587.88) In choledochal cancer, rs25487_CT was observed in 15.87% (10/63) vs 40% of C1 (24/60), p=0.0052, OR=0.28 (0.11-0.71) and 36.92% of C2 (48/130), p=0.0047, OR=0.32 (0.14-0.73), while C/C genotype, 74.60% of (47/63) vs 57.69% of C2 (75/130), p=0.0335, OR=2.15 (1.06-4.43).

Conclusion: In Mexican population, our results suggest that XRCC1rs1799782 genotype A/A is risk factor in choledochal cancer, and SNP rs25487 is protective factor while in gallbladder cancer, SNP rs1799782 is a risk factor.

Disclosure of Interest: None declared

P0684 FREQUENCY OF MUTATIONS IN KRAS, MET AND PIK3CA IN EXTRAHEPATIC CHOLANCHIOCARCINOMA IN MEXICAN PATIENTS

A. Guitron¹, F. K. Segura-Lopez², J. Torres³, F. Lopez-Marquez⁴, S. Leon-Carballo⁵, L. Guerrero-Perez⁶, J. Garcia-Correa⁷, A. Hernandez-Guerrero⁸, G. Alfaro-Fattel⁹, F. Canzian¹⁰

¹Gastrointestinal Endoscopy, ²Surgery, Mexican Institute of Social Security, Torreon, ³Infectious Diseases Research Unity, Mexican Institute of Social Security, Mexico DF, ⁴Molecular Immunobiology Department, Autonomus University of Coahuila, Torreon, ⁵Gastrointestinal Endoscopy, ISSSTECH, Tuxtla Gutierrez, Chiapas, ⁶Gastrointestinal Endoscopy, Mexican Institute of Social Security, Juarez, Chihuahua, ⁷Gastrointestinal Endoscopy, Mexican Institute of Social Security, Guadalajara, Jalisco, ⁸Gastrointestinal Endoscopy, Cancer National Institute, ⁹Gastrointestinal Endoscopy, Mexican Institute of Social Security, Mexico DF, Mexico, ¹⁰Genetic Epidemiology Department, DKFZ German Cancer Research Center, Heidelberg, Germany

Contact E-mail Address: aguitron@prodigy.net.mx

Introduction: Extrahepatic cholangiocarcinoma (ECC) is a rare but a highly lethal malignancy due to difficulties of early diagnosis and lack of effective therapies. In Mexico endoscopic retrograde cholangiopancreatography (ERCP) still is considered a valuable tool for assessing biliary tract strictures because it allows obtain radiological images biliary tract, therapeutic interventions, and collection of brushing cytology specimens although highly specific, has low/moderate sensitivity (15%>68%). The progress in molecular biology of human cancers along with increased understanding of oncogenic mutations and cell signaling pathways, led to the successful application of mutation analysis as a part of diagnostic techniques as well as new targeted therapies in many solid tumors. The mass spectrometry technique, matrix-assisted laser desorption/ionization–time of flight, has been used to assess tumors for point mutations and small deletions in commonly altered oncogenes.

Aims & Methods: The goal was determine the frequency of somatic mutations in common oncogenes in ECC in epithelial cells obtained by scraping the biliary ducts. Multicenter study performed in Mexico between May 2012 December 2013, included adults with diagnosis of ECC by ERCP, plus endoscopic ultrasound, intraductal biliary ultrasound and direct cholangioscopy. All cases were confirmed by brush cytology, histopathology and clinical course. Epithelial cells were obtained by scraping the biliary ducts during ERCP and the brushes were suspended in buffer solution at -80°C until tested. DNA was extracted from brushed cells using the QIAamp DNA easy kit and quantified using the PicoGreen kit, and evaluated using the Sequenom MassARRAY and OncoCarta v1.0 Mutation Profiler Panel.

Results: Included 28 cases: 17 woman and 11 men, mean age 64.41 ± 14.74, the ECC was distributed; 14 (50%) choledocho, 4 (14.29%) gallbladder and 10 (35.71%) in ampulla of Vater. Mutations were identified in 39.29% (11/28) of ECC in follow genes KRAS 28.57% (8/28); G12D, MET 7.14% (2/28); T992I, M1250T and PIK3CA 3.57% (1/28); P539R. The highest mutation rate was observed in cancer of choledocho 42.86% (6/14), followed by ampulla of Vater 40% (4/10) and gallbladder 25% (1/4). Follow-up was 30 months. Survival in patients without mutations was 9.25 ± 6.56 months and 9.78± 3.73 months in patients with mutations without significance.

Conclusion: Mutations in oncogenes as KRAS, MET and PIK3CA decrese efficacy of specific chemotherapies and in our study this frequency was 39.29% of ECC. MassARRAY technology can be used to detect mutations in a wide variety of oncogenes using epithelial cells obtained by scraping biliary ducts during ERCP and could be used for molecular profile in ECC protocol as diagnosis tool and individualized therapy.

Disclosure of Interest: None declared

P0685 CHITOSAN NANOPARTICLES FOR THE DELIVERY OF A PHOTOSENSITIZER TO HUMAN CHOLANGIOCARCINOMA CELLS

O. Sook Kyoung¹, K. Dae Hwan¹, K. Hyung Wook¹, C. Cheol Woong¹, P. Su Bum¹, K. Su Jin¹, K. Tae Sung¹

¹Internal Medicine, Pusan National University, Yangsan Hospital, Yangsan, Republic of Korea

Contact E-mail Address: gon22gon@naver.com

Introduction: Chitosan is known as a natural and biocompatible polymer which has immune adjuvants and anticancer activities. Therefore, chitosan can be used in drug such as Ce6 that is adaptable to incorporate anionic drug because of the cationic properties of chitosan.

This study was produced using the water-soluble chitosan incorporated nanoparticles containing Ce6. Photodynamic potentials and physicochemical properties of Ce6-incorporated chitosan nanoparticles were studied against human cholangiocarcinoma cells in vitro and in vivo.

Aims & Methods: We purchased chitosan from Kittolife Co. Korea and Ce6 from Frontier Sci. Co. Ltd. USA.

We fabricated Ce6-incorporated nanoparticles using chitosan by dissolving 100mg of chitosan in 10ml of deionized water. Then 5-20 mg of Ce6 in 0.5ml DMSO was added to chitosan solution following sonication using bar-type ultrasonicator. To remove organic solvent and free drug, this solution was dialyzed against water.

Results: Ce6-incorporated nanoparticles was fabricated through ion-complexation formation between amine group of chitosan and carboxyl group of Ce6 using water-soluble chitosan. By simple mixing of Ce6 and chitosan, photosensitizer-incorporated were prepared following sonication and dialysis which has spherical shapes with less than 500nm. When Ce6-incorporated nanoparticles were treated to human cholangiocarcinoma cells with irradiation, they enhanced delivery of Ce6 to human cholangiocarcinoma cells and then enhanced ROS level in tumor cells rather than free Ce6. Futhermore, nanoparticles enhanced treatment efficiency. Photo-induced toxicity against human cholangiocarcinoma cells were increased compared to Ce6 only treatment. Nanoparticles enhanced delivery of Ce6 through bile duct in ex vivo study using porcine bile duct slice. Also, nanoparticles significantly enhanced delivery of Ce6 to tumor at in vivo animal study.

Conclusion: Ce6-incorporated nanoparticles using water-soluble chitosan were prepared. ChitoCe6 nanoparticles enhanced cellular uptake, phototoxicity, and ROS generation compared to Ce6i only. Also, Ce6-incorporated nanoparticles enhanced delivery to human cholangiocarcinoma cells in vivo animal study and ex vivo porcine bile duct slice experiment.

Disclosure of Interest: None declared

P0686 PROMISING CANDIDATE FOR VORINOSTAT-INCORPORATED NANOPARTICLES AGAINST HUMAN CHOLANGIOCARCINOMA CELLS

K. Su Jin¹, O. Sook Kyoung¹, K. Dae Hwan¹, K. Hyung Wook¹, C. Cheol Woong¹, P. Su Bum¹, K. Min Dae², R. Dae Gon¹

¹Department of Internal Medicine, Pusan National University, Yangsan Hospital, Yangsan, ²Department of Internal Medicine, Bong Seng Memorial Hospital, Pusan, Republic of Korea

Contact E-mail Address: gon22gon@naver.com

Introduction: This study evaluates the anticancer activity of vorinostat-incoporated nanoparticles (vorinostat-NPs) against cholangiocarcinoma cells.

Aims & Methods: By using a nanoprecipitation method, Vorinostat-NPs were fabricated and presented its spherical shapes with small particles size less than 100 nm. Also, Vorinostat-NPs were coated onto covered-stent. We observe the anticancer activity of Vorinostat-NPs and their coated stent in vitro and in vivo.

Results: Vorinostat and vorinostat-NPs have similar anticancer efficacy in terms of cytotoxicity, cell growth inhibition, and apoptosis of HuCC-T1 cholangiocarcinoma cells in vitro. Also, they have equal potency in inhibition of histone deacetylase (HDAC) expression, mutant type p53 suppression, increased p21expression, and PARP/cleaved caspase-3 expression. However, vorinostat-NPs and their coated stent showed improved antitumor activity against HuCC-T1 cancer cell-bearing mice compared to vorinostat itself, whereas empty nanoparticles had no effect on tumor growth. Vorinostat-NPs increased the expression of acetylated histone H3 in tumor tissue and suppressed HDAC expression in vivo. The improved anticancer efficacy of vorinostat-NPs was confirmed by molecular imaging studies using NIR-dye-incorporated nanoparticles.

Conclusion: This study shows the anticancer activity of vorinostat and vorinostat-NPs against HuCC-T1 cholangiocarcinoma cells by specific inhibition of HDAC expression. Therefore, vorinostat-NPs can be used in anticancer chemotherapy in cholangiocarcinoma.

Disclosure of Interest: None declared

P0687 PRE-EXPOSURE WITH SIMVASTATIN INHIBITS LIPOPOLYSACCHARIDE-INDUCED EPITHELIAL-MESENCHYMAL TRANSITION VIA DOWNREGULATION OF TLR4 AND NF-KB IN HUMAN BILIARY EPITHELIAL CELLS

S. M. Park¹, Y. Kim², B. Cho¹, Y. Oh¹

¹Internal Medicine, Chungbuk National University Hospital, ²Physiology, Chungbuk National University College of Medicine, Cheongju, Republic of Korea

Contact E-mail Address: smpark@chungbuk.ac.kr

Introduction: Epithelial-mesenchymal transition (EMT) of biliary epithelial cells (BECs) plays a role in biliary fibrosis. Lipopolysaccharide (LPS) promotes EMT in BECs.

Aims & Methods: The present study investigated the effects of simvastatin on the EMT of BECs induced by LPS. Transformed human BECs (H69) were exposed with LPS (1μg/mL) or transforming growth factor-β1 (TGF-β1, 5 ng/ml) for 5 days. The expression of E-cadherin, vimentin, N-cadherin, and toll-like receptor 4 (TLR4) was determined by quantitative real-time PCR, western blotting, and confocal microscopy. The effect of simvastatin on the EMT induced by LPS or TGF- β1 was determined by the expression of E-cadherin, vimentin, and TLR4.

Results: After exposure to 1μg/mL of LPS for 5 days, E-cadherin decreased and vimentin increased in mRNA and protein levels. The mRNA expression of TRL4 was increased by the exposures of LPS and TGF-β1 (5ng/ml) for 5 days. As compared with BECs treated with LPS alone, co-treatment with simvastatin plus LPS showed a remarkable increase of E-cadherin and a slight decrease of vimentin. LPS-induced TLR4 slightly decreased by co-treatment with simvastatin and LPS. In the proliferation analysis, LPS-induced BECs growth was remarkably inhibited by the application of simvastatin (1μM). In BECs morphology analysis, as compared with BECs pre-treatment with simvastatin before LPS exposure (preSL), BECs pre-exposure with LPS (postSL) or co-exposure with LPS plus simvastatin (LS) were more potentiated EMT effects (cell morphology changes round shape to spindle like morphology). Furthermore, BECs pretreated with simvastatin (preSL) inhibited LPS-induced EMT by downregulation of NF-kB phsophorylation. These findings indicate that, while LPS or TGF-β1 promoted EMT, the BECs pre-treated with simvastatin (preSL) inhibited LPS-induced EMT by downregulation of TLR4 and NF-kB.

Conclusion: Our results demonstrate that pre-exposure with simvastatin (preSL) inhibits the LPS-induced EMT of human BECs. This finding suggests that simvastatin can be considered as a new agent to prevent biliary fibrosis associated with EMT of BECs.

Disclosure of Interest: None declared

P0688 ANALYSIS OF DISCREPANCY IN RADIOLOGIC AND PATHOLOGIC DIAGNOSIS OF GALLBLADDER ADENOMYOMATOSIS

S. H. Kang¹, J. H. Lee¹, I. K. Yoo¹, S. H. Kim¹, J. M. Lee¹, H. S. Choi¹, E. S. Kim¹, B. Keum¹, Y. T. Jeen¹, H. J. Chun¹, H. S. Lee¹, C. D. Kim¹

¹Division of Gastroenterology and Hepatology, Department of Internal Medicine, Institute of Gastrointestinal Medical Instrument Research, Korea University College of Medicine, Seoul, Republic of Korea

Contact E-mail Address: thirky@hanmail.net

Introduction: Adenomyomatosis of gallbladder (GB) is considered as benign condition, but several reports suggest association with malignancies, especially for segmental subtype. Because of this chance, patients suspected to have segmental or diffuse type adenomyomatosis on the imaging study may undergo cholecystectomy. But, in some cases, histopathology reveals only chronic inflammation. In this study, we aimed to analyze radiologic and pathologic features of chronic cholecystitis and adenomyomatosis for more accurate diagnosis.

Aims & Methods: Patients who performed cholecystectomy during recent four years in one medical center were reviewed retrospectively. Among those, patients who were suspected to have adenomyomatosis on their abdominal imaging but with no adenomyoma detected on the histopathologic examination were analyzed for their radiologic, pathologic and clinical features compared to patients who had consistent results between abdominal imaging and histopathologic examination.

Results: Among 3144 patients who underwent cholecystectomy, 358 patients were suspected to have GB adenomyomatosis on the abdominal imaging study. Among them (358 patients), only 92 patients had histopathologic findings compatible with adenomyomatosis. Remaining 266 patients (74.3%) did not have adenomyomatosis. Instead, many GB specimens showed chronic cholecystitis. In this group, diffuse subtype of adenomyomatosis was significantly frequent compared to 92 patients who had coherent adenomyoma finding for both imaging study and pathology. The frequency of accompanying GB stones was significantly higher in mismatching group. Radiologically, contour of GB wall thickening, intralesional cystic area and inner layer enhancement pattern was helpful in differentiating adenomyomatosis from chronic cholecystitis.

Conclusion: Chronic cholecystitis mimicking adenomyomatosis is difficult to diagnose solely based on the abdominal imaging, and this can lead to unnecessary cholecystectomy. Existence of gallstones and several radiologic features can help differentiate these challenging entities.

Disclosure of Interest: None declared

P0689 THE EFFICACY OF VARIOUS ENDOSCOPIC TRANSPAPILLARY SAMPLING METHODS FOR MALIGNANT BILIARY LESIONS

H. S. Lee¹, S. H. Kim¹, I. K. Yoo¹, J. M. Lee¹, H. S. Choi¹, E. S. Kim¹, B. Keum¹, Y. T. Jeen¹, H. J. Chun¹, C. D. Kim¹, J. J. Hyun²

¹Division of Gastroenterology and hepatology, Department of Internal Medicine, Institute of Gastrointestinal Medical Instrument Research, Korea University College of Medicine, Seoul, ²Department of Internal Medicine, Division of Gastroenterology and Hepatology, Korea University Ansan Hospital, Ansan, Republic of Korea

Contact E-mail Address: kimseunghan09@gmail.com

Introduction: Various methods for endoscopic transpapillary sampling have been developed. However, the accuracy rate of these methods for bile duct cancer are controversial. The aim of the present study was to determine the factors affecting the accuracy of endoscopic transpapillary sampling methods.

Aims & Methods: We reviewed the results from 92 patients with bile duct cancer who underwent transpapillary sampling by aspiration bile cytology, brushing cytology, and fluoroscopic forceps biopsy. The final diagnosis of bile duct cancer was made on the basis of pathological evaluation of specimens obtained at surgery or the clinical course over at least 1 year in patients not operated. We carried out subgroup analyses for the factors affecting the accuracy of each transpapillary sampling method.

Results: Transpapillary biopsy (71.2%) had a significantly higher level of sensitivity for cholangiocarcinoma than brush cytology (58.8%) and bile cytology (62.5%). Bile cytology (85.7%) showed higer diagnostic yield for pancreatic cancer with bile duct invasion than transpapillary biopsy (60%) and brush cytology (66.7%). In patients with negative biopsy results, bile cytology had higher diagnostic yield than brush cytology.

Conclusion: Transpapillary bile duct biopsy is a simple, safe, and effective technique for diagnosing biliary malignant lesion. It showed more sensitive for cholangiocarcinoma than for pancreatic cancer with bile duct invasion. After negative biopsy result, bile cytology presented higher diagnostic yield.

Disclosure of Interest: None declared

P0690 MULTIPLE METAL STENTS FOR COMPLEX MALIGNANT HILAR STRICTURES: PATIENTS SURVIVAL, STENTS PATENCY AND OUTCOMES OF RE-INTERVENTIONS FOR OCCLUDED STENTS

I. Boskoski¹, S. Greco¹, P. Familiari¹, A. Tringali¹, V. Perri¹, G. Costamagna¹

¹Digestive Endoscopy Unit, Catholic University of Rome, Rome, Italy

Contact E-mail Address: ivoboskoski@yahoo.com

Introduction: Endoscopic biliary drainage of malignant hilar biliary strictures (MHS) with self-expandable metal stents (SEMS) is a well-established palliative treatment for unresectable hilar tumors. Efficacy of SEMS has been well described in distal biliary strictures, but data in complex MHS are lacking.

Aims & Methods: Retrospective review of a prospective database of all patients with MHS that underwent ERCP for symptoms palliation. Of these, only patients with multiple SEMS placement were included. Survival-associated factors and stents patency were analyzed by Cox multivariate analysis. Patients survival, stents patency and outcomes of re-interventions for occluded stents were evaluated.

Results: Between January 1998 and June 2014, 740 patients with complex MHS that underwent ERCP for palliation were identified. Among these, 134 (18.2%) patients were treated with two or more multiple SEMS. Of the 134 patients, 76 (56.7%) previously had plastic stents, 34 (25.4%) had one or more percutaneous biliary drainages and 24 patients (17.9%) received SEMS as first treatment. Mean age at time of diagnosis was 67.2 (SD26.8) years, female patients were 53.7%. Histologically, cholangiocarcinoma was the cause of stricture in 59% of patients, while 28.3% had gallbladder carcinoma. Hilar compression by lymphnodes and hilar hepatocellular carcinoma had 9.7% and 3% respectively. Regarding the Bismuth type of hilar stricture, 25.3% had type II, type III had 50.7% and type IV had 24% of the patients. Chemotherapy was done in 38.3% of patients, external-beam radiotherapy in 12.7% and high-dose-rate brachytherapy in 10%. Multiple SEMS were placed “side-by-side” after 2 to 4 guidewires were left in place into the ducts to be drained. Post-procedure complications (5.2%: 4 sphincterotomy bleedings, 3 pancreatitis) were managed conservatively. No procedure-related mortality was observed. Histological and follow-up data were available for all of the 134 patients. Seventy-nine (59%) patients died without clinical signs of SEMS occlusion, while 55 (41%) patients had SEMS occlusions and underwent ERCP. Overall mean survival of the 134 patients was 380 days (28-1455). Survival was not influenced by tumor or Bismuth type, palliative chemotherapy, sex or age (P=0.5). Longer survival was found in patients that underwent high-dose rate brachytherapy with Iridium 192 (P=0.02), but not in those that underwent external beam radiotherapy (P=0.8). The 55 patients that had SEMS occlusion underwent 93 endoscopic re-interventions (1-6/patient) after mean 201.3 days (32-867) from the first multiple SEMS insertion and mean 140 days (30-330) between further re-interventions. Main causes for SEMS occlusion were due to sludge, overgrowth and ingrowth. Sludge was removed with balloon and flushing with saline, while plastic stents or SEMS were placed into the previous SEMS in cases of ingrowth and overgrowth. Overall mean survival after re-interventions was 432 days (91-1425) and was prolonged compared to patients that died without signs of stents occlusion (P=0.001).

Conclusion: Endoscopic insertion of multiple SEMS is safe and effective in patients with complex MHS. Survival is satisfactory independently from age, sex and type of tumor. High-dose rate brachytherapy and prompt recognition of signs of SEMS occlusion are associated with prolonged survival.

Disclosure of Interest: None declared

P0691 RISK FACTORS OF GALLBLADDER NEOPLASMS IN SUSPICIOUS ADENOMYOMATOSIS ON COMPUTED TOMOGRAPHY

J. Kang¹, J. Hwang¹, J. Kim¹, K. Paik¹, H. Kim¹, J. Lee¹

¹Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea

Contact E-mail Address: bjpgr@naver.com

Introduction: Gallbladder (GB) adenomyomatosis is not uncommon findings on computed tomography (CT). Sometimes, the lesions are confirmed as GB neoplasms (adenoma or carcinoma). However, it is quite difficult to diagnose adenomyomatosis when showing GB wall thickness on CT.

Aims & Methods: The aim of this study is to find out predictors which may indicate GB neoplasms in suspicious GB adenomyomatosis on CT before cholecystectomy.

Patients with suspicious GB adenomyomatosis on CT (the presence of one or more of the following CT findings; mucosal epithelium with intramural diverticula, multiple intramural cysts, discrete hypoattenuating lesions) and underwent cholecystectomy between January 2010 and February 2015 were reviewed retrospectively. They were divided into three groups based on the pathologic findings: chronic cholecystitis group (n=144), adenomyomatosis group (n=92) and GB neoplasms group (n=13). The clinical data and CT findings were compared between the three groups.

Results: A total of 249 patients were enrolled. There was no differences between chronic cholecystitis, adenomyomatosis and neoplasms groups in terms of clinical characteristics except age (50.4y vs. 50.6y vs. 64.3y, respectively, p < 0.001). Moreover, morphologic types (diffuse, fundal and segmental) on CT did not predict GB neoplasms. When further analyzing between adenomyomatosis group and GB neoplasms group, older age, combined GB polyp, and GB wall enhancement were independent risk factors on GB neoplasms with statistical significance.

Conclusion: We suggest that older age, combined GB polyp, and GB wall enhancement are independent risk factors on GB neoplasms in suspicious GB adenomyomatosis on CT. Therefore, the older with suspicious adenomyomatosis would be needed further evaluations, when combined GB polyps or GB wall enhancement.

Disclosure of Interest: None declared

P0692 PREDICTABLE FACTORS FOR PANCREATICOBILIARY MALIGNANCY IN PATIENTS WITH ANOMALOUS UNION OF PANCREATICOBILIARY DUCT

J.-S. Park¹, T. J. Song², D. H. Park³, S. S. Lee³, D. W. Seo³, S. K. Lee³, M.-H. Kim³, D. Oh³

¹Gastroenterology, Inha University Hospital, Incheon, ²Asan Medical Center, Seoul, Republic of Korea, ³Gastroenterology, Asan Medical Center, Seoul, Republic of Korea

Contact E-mail Address: pjsinha@naver.com

Introduction: Anomalous union of the pancreaticobiliary duct (AUPBD) is a rare congenital anomaly in which the pancreatic and biliary ducts join anatomically outside of the duodenal wall, usually forming a markedly long common channel. The most clinically important feature of AUPBD is frequently associated with carcinomas of the biliary tract, i.e., bile duct and gallbladder. Evaluation of AUPBD-related pancreaticobiliary malignancies is essential to determining appropriate treatment of anomalous union of pancreaticobiliary duct (AUPBD).

Aims & Methods: The aim of this study is to determine the incidence of AUPBD-related pancreaticobiliary malignancies and to propose their predictable factors. We retrospectively reviewed data from 229 patients with AUPBD between January 1999 and December 2013. The incidence of AUPBD-related pancreaticobiliary diseases, particullary according to the presence of bile duct dilatation and the predictable factors for pancreaticobiliary malignancies were evaluated.

Results: Among 229 patients with AUPBD, 152 patients had common bile duct dilatation (≥10 mm) (dilated group) and 77 patients did not have bile duct dilatation (<10 mm) (non-dilated group). Intrahepatic cholangiocarcinoma (ICC) occurred more frequently in the non-dilated group than in the dilated group (non-dilated group vs. dilated group; 3.9% vs. 0%, P <0.05). On the other hand, although extrahepatic cholangiocarcinoma (ECC) tended to occur more frequently in the dilated group (1.3% vs. 3.9%, P value=0.271), there were no significant differences in most pancreaticobiliary diseases between the two groups. In univariate analysis to determine predictable factors for AUPBD-related biliary tract cancer, age, type of AUPBD, and refluxed pancreatic enzyme level in bile duct showed significant differences. In multivariate analysis, age ≥45 years (OR, 1.042; 95% CI, 1.011-1.073; P <0.05), P-C type (OR, 3.327; 95% CI, 1.031-10.740; P < 0.05), and a high level of biliary lipase (OR, 4.132, 95% CI, 1.420-12.021; P < 0.05) showed a significant association with AUPBD-related biliary tract cancer.

Conclusion: ICC may occur more frequently in AUPBD patients without bile duct dilatation. Age ≥45 years, P-C type, and biliary lipase level ≥45,000 IU/L are significantly related to AUPBD-related biliary tract cancer.

Disclosure of Interest: None declared

P0693 LONG-TERM FOLOW-UP OF ENDOSCOPIC PAPILLECTOMY (PE) IN PATIENTS WITH MALIGNANCY OF THE MAJOR DUODENAL PAPILLA

J. C. Ardengh¹², E. Taglieri², O. Micelli-Neto², E. T. Ardengh², R. Kemp¹, J. S. dos-Santos¹

¹Surgery and Anatomy of HCFMRP-USP, HCFMRP-USP, Ribeirão Preto, ²Endoscopy Departament, Hospital 9 de Julho, São Paulo, Brazil

Contact E-mail Address: jcelso@uol.com.br

Introduction: The Endoscopic Papillectomy (EP) still is a controversial procedure used to treat malignancy of the major duodenal papilla. Nowadays, the treatment chosen is duodenopancreatectomy. The aims of of this transversal and multicentric study was to establish the endoscopic treatment parameters of malignancy of the major duodenl papilla in a controlled group of patients.

Aims & Methods: From January of 2008 to June of 2014, 54 patients were referred to undergo EP after staging by endosonography. We analyzed the occurrence of adverse events, relapses and the median follow-up results of 21.3 (3-96) months. We included those whose final diagnosis was adenocarcinoma, adenoma with high-grade dysplasia or neuroendocrine tumor of the major papilla.

Results: The endoscopic biopsy shown the diagnostic of malignancy in 45% (20/54) of cases. The majority (13/20 - 65%) had jaundice at the time of the exam. The total number of patients who met the inclusion criteria was 20: 15 with the histologic diagnosis of adenocarcinoma, three with neuroendocrine carcinoma and two with adenoma with high-grade dysplasia. The resection was complete in 18/20 (90%). Adverse events occurred in 7/20 (35%): the most frequent was bleeding (3/20 - 15%), followed by acute pancreatitis (2/20 - 10%). 14 (70%) of the selected patients keep monitoring and have no sign of the disease. Six patients were submitted to surgical treatment, and three of them had residual lesion (1 with pT1 and 2 with pT3) and metastatic lymph nodes in the surgical specimen (1 with pTxN1 and 2 with pT3N1). The main indication for surgery was the final diagnosis of EP product and the involvement of the lateral and deep margin of the lesion.

Conclusion: The EP is a safe and effective procedure for the treatment of the malignnacy of the papilla. The involvement of deep and lateral resection margins was determinant to the surgical indication. To optimize the approach of the carcinomas of major duodenal papilla endoscopically, we should expect a diligent patient selection, reference centers and specialized team.

Disclosure of Interest: None declared

P0694 LONG-TERM FOLLOW-UP OF ENDOSCOPIC PAPPILLECTOMY (EP) IN PATIENTS WITH MALIGNANCY OF THE MAJOR DUODENAL PAPILLA

J. C. Ardengh¹², E. Taglieri², O. Micelli-Neto², E. T. ARDENGH², R. Kemp³, J. S. dos Santos¹

¹Surgery and Anatomy of HCFMRP-USP, HCFMRP-USP, ²Endoscopic Department, Hospital 9 de Julho, São Paulo, ³Surgery and Anatomy of HCFMRP-USP, HCFMRP-USP, Ribeirão Preto, Brazil

Contact E-mail Address: jcelso@uol.com.br

Introduction: The EP is still controversial procedure used to treat malignancies of the major duodenal papilla. Nowadays, the best treatment for this disease is duodenopancreatectomy.

Aims & Methods: The aim of this transversal and multicentric study was to establish the best parameters of the endoscopic treatment in patients with a malignant tumor of the major duodenal papilla tumor. From January of 2008 to June of 2014, 54 patients were referred to undergo EP after endosonography staging. We analyzed the occurrence of adverse events, relapses and the median follow-up results of 21.3 (3-96) months. We included those whose final diagnosis was adenocarcinoma, adenoma with high-grade dysplasia or neuroendocrine carcinoma.

Results: The endoscopic biopsy shown the diagnostics of malignancy in 45% (20/54) of cases. The majority (13/20 - 65%) had jaundice at the time of the exam. The total number of patients who met the inclusion criteria was 20: 15 with the histologic diagnosis of adenocarcinoma, three with neuroendocrine carcinoma and two with adenoma with high-grade dysplasia. The resection was complete in 18/20 (90%). Adverse events occurred in 7/20 (35%): the most frequent was bleeding (3/20 - 15%), followed by acute pancreatitis (2/20 - 10%). 14 (70%) of the selected patients keep monitoring and have no sign of the disease. Six patients were submitted to surgical treatment, and three of them had residual lesion (1 with pT1 and 2 with pT3) and metastatic lymph nodes in the surgical specimen (1 with pTxN1 and 2 with pT3N1). The main indication for surgery was the final diagnosis of EP product and the involvement of the lateral and deep margin of the lesion.

Conclusion: The EP is a safe and effective procedure for the treatment of papillary tumors. The involvement of deep and lateral resection margins was determinant to the surgical indication. To optimize the approach of the malignancies of major duodenal papilla endoscopically, we should expect a diligent patient selection, reference centers and specialized team.

Disclosure of Interest: None declared

P0695 OPTIMIZATION OF TISSUE ABLATION PARAMETERS FOR ENDOBILIARY RADIOFREQUENCY IN PORCINE LIVER, BILE DUCTS AND AMPULLA OF VATER

M. Barret¹, S. Leblanc¹, A. Vienne¹, A. Rouquette², S. Chaussade¹, F. Prat¹

¹Gastroenterology, ²Pathology, Cochin Hospital, Paris, France

Contact E-mail Address: frederic.prat@aphp.fr

Introduction: The extent of thermal tissue injury induced by endoscopic endobiliary radiofrequency ablation has been described only for a select set of parameters designed to treat malignant strictures of the common bile duct. Since potential indications of this therapeutic modality may also include shallow intrahepatic or ampullary lesions, we sought to determine the optimal generator settings for such indications.

Aims & Methods: Endobiliary radiofrequency ablation was performed in live swine on the ampulla of Vater, in the common bile duct and hepatic parenchyma. Radiofrequency ablation time, “effect”, and power were allowed to vary. The animals were sacrificed 2 hours after the procedure. Histopathological assessment of the depth of thermal lesions was performed.

Results: Twenty-five radiofrequency bursts were applied in three swine. In the ampulla of Vater (n= 3), necrosis of the duodenal wall was observed starting with an effect set at 8, power output set at 10 W and a 30s shot duration, whereas superficial mucosal damage of up to 350µm in depth was recorded for an effect set at 8, a power output set at 6W and a 30 s shot duration. In the common bile duct (n=4), a 1070 µm safe and efficient ablation was obtained for an effect set at 8, a power output of 8W, and an ablation time of 30 s. Within the hepatic parenchyma (n=18), the depth of tissue damage varied from 1620µm (effect =8, power =10W, ablation time =15 s) to 4480µm (effect =8, power =8W, ablation time = 90 s).

Conclusion: The duration of catheter application appeared to be the most important parameter influencing the depth of thermal injury during endobiliary radiofrequency ablation. In healthy swine, currently recommended settings of the generator may induce severe, supratherapeutic tissue damage in the biliary tree, especially in the high-risk area of the ampulla of Vater.

Disclosure of Interest: None declared

TUESDAY, OCTOBER 27, 2015   09:00-17:00

PAEDIATRIC: LIVER, BILIARY & PANCREAS – HALL 7__________

P0696 ROLE OF PROCALCITONIN AND C-REACTIVE PROTEIN AS BIOMARKERS OF INFECTION IN CHILDREN WITH LIVER DISEASE

A. Srivastava¹, R. Bolia¹, R. Marak², S. K. Yachha¹, U. Poddar¹

¹Pediatric Gastroenterology, ²Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

Contact E-mail Address: avanianshu@yahoo.com

Introduction: Infection with organ failure is an important cause of mortality in patients with liver disease. Early and accurate identification of infection in these patients is challenging.

Aims & Methods: This study evaluated the role of procalcitonin (PCT) and C-reactive protein (CRP) as biomarkers of bacterial infection in children with liver disease.

Demographic and clinical data of consecutive children admitted with acute liver failure (ALF) or decompensated chronic liver disease (DCLD) were collected prospectively. Children were evaluated for infection at admission with hemogram including total and differential leukocyte count, PCT, CRP, blood and urine culture, chest X-ray and ascitic fluid analysis including culture in those with ascites. Systemic inflammatory response syndrome (SIRS) and severe sepsis were defined as per the International pediatric sepsis consensus definition¹.

Results: 164 children (113 boys, age 76(0.5 – 204) months, ALF =69, DCLD=95) were enrolled. 77 (47%) subjects had infection, most common site being ascitic fluid (AFI, n= 35), followed by urinary tract (UTI, n = 26), pneumonia (n = 22) and blood stream infection (BSI, n= 16). 21 children had multiple site infections, 18 had severe sepsis and 36 had SIRS.

Subjects with infection had significantly higher PCT (1.7 [ 0.1 – 38.1] ng/ml vs.0.3 [0.1 – 6.8] ng/ml; p = 0.00), CRP (1.82 [0.3 – 24] mg/dL vs. 0.33 [0.1 – 4.2] mg/dL, p = 0.00) and TLC (14,000 [3600 – 43800] /mm³ vs. 8800 [ 3800 – 39600] /mm³, p = 0.00) as compared to those without infection. Presence of fever did not help in differentiating patients with and without infection (27/77 vs. 20/87, p=0.1). PCT and CRP values were not different in patients with various sites of infection i.e. BSI, AFI, UTI or pneumonia. PCT and CRP correlated with infection severity, highest in severe sepsis [8.3(3.5 – 38) ng/mL and 4.1(0.3 – 13.8) mg/dL] than infection [0.89 (0.1– 8) ng/mL and 1.7 (0.32-24) mg/dL] than no infection [0.3 (0.1 – 6.75) ng/mL and 0.3 (0.1 – 4.16 mg/dL). Sensitivity, specificity and likelihood ratio (LR) of CRP, PCT and TLC in identifying infection in children with liver disease is shown in Table 1. SIRS was commoner in patients with infection (31/77 vs. 5/87, p = 0.00). PCT (> 0.5 ng/ml) and CRP (>0.6 mg/dL) performed better in DCLD (AUC of 0.90 and 0.83) as compared to ALF patients (AUC of 0.73 and 0.69).

Abstract number: P0696

Decompensated chronic liver disease		Sensitivity (%)	Specificity (%)	LR-positive	LR-negative
	CRP(> 0.6 mg/dL)	86.8	73.8	3.31 (1.8-4.86)	0.17 (0.11-0.41)
	PCT(>0.5 ng/ml)	86.8	91.7	10.4 (3.5-23.28)	0.15 (0.07-0.29)
	TLC	43.4	71.4	1.52 (0.86-2.67)	0.79 (0.58-1.07)
	PCT + CRP	79.2	91.7	9.54 (3.2-21.3)	0.23 (0.13-0.39)
PCT + CRP + TLC	43.4	92.8	6.08 (1.9 – 18.6)	0.61 (0.47 – 0.78)
Acute liver failure	CRP(> 0.49 mg/dl)	75	67	2.27 (1.12-3.14)	0. 37 (0.22-0.98)
	PCT(> 0.5 ng/ml)	83.3	57.8	1.97 (1.34-2.9)	0.29 (0.11-0.73)
	TLC	41.6	73.3	1.56 (0.79-3.08)	0.79 (0.34-0.94)
	PCT + CRP	62.5	75.5	2.56 (1.4-4.6)	0.5 (0.29-0.85)
PCT + CRP + TLC	37.5	88.9	3.37(1.27 – 8.94)	0.7(0.5 – 0.97)

Conclusion: PCT and CRP are reliable markers of infection and correlate with infection severity in children with liver disease. Their diagnostic accuracy is better in DCLD than ALF cases. SIRS is significantly more common in patients with infection.

Disclosure of Interest: None declared

P0697 THE CLINICAL EFFECT AND CHANGES OF MICROFLORA UNDER PROBIOTIC SUPPLEMENTATION IN CHILDREN WITH BILIARY ATRESIA - A RANDOMIZED CONTROLLED TRIAL

E. Orlowska¹, P. Czubkowski², I. Motyl³, E. Klewicka³, Z. Libudzisz³, P. Socha⁴

¹Gastroneterology, Hepatology, Nutritional Disorders and Pediatrics, ²Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, ³Institute of Fermentation, Lodz, ⁴Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Childrens Memorial Health Institute, Warsaw, Poland

Contact E-mail Address: p.socha@czd.pl

Introduction: Due to the modulatory effect on intestinal microflora, probiotics could be potentially used to prevent complication after hepatoportoenterostomy in children with biliary atresia, which can lead to progression of liver disease and require liver transplantation.

Aims & Methods: In this study we aimed at evaluating LGG probiotic treatment during the course of biliary atresia after the hepatoportoenterostomy in respect of clinical outcomes, liver function tests, gut microflora and intestinal barrier.

The patients were randomly assigned to two groups ingesting probiotic or placebo (1:1). The active preparation was the LGG probiotic (Lactobacillus GG) administered as capsuled powder (Dicoflor 60 preparation) for 6 months. Initially, after 3, 6 and 9 months the following parameters were assessed: A. anthropometric B. laboratory C. stool examination:- quantitative assessment of the gut microbiota composition by growing methods with the use of non-selective (differential) and selective growth media; quantitative assessment of the short-chain fatty acids (acetic, butyric and priopionic) and lactic acid; Alpha-1 Antitrypsin (A1AT) concentration in stool as a marker of intestinal barrier permeability.

The study included 30 children: 13 girls and 17 boys aged <4 months suffering from chronic cholestasis in the course of bile duct obstruction. In all patients, the bile duct obstruction diagnosis was intraoperatively confirmed and the Kasai portoenterostomy was performed.

Results: After 6 months there were 3 children in the LGG group suffering from at least one ascending cholangitis episode compared to 8 children in the placebo group, which was not statistically different. The number of all infections amounted to 6 in the LGG group and 12 in the placebo patients (ns). During the intervention, 7 out of 14 patients taking LGG and 5 out of 16 placebo patients were qualified for liver transplantation (no statistical difference).The level of conjugated bilirubin decreased below 2 mg/dl during the 6 months long trial in 6 patients in the LGG group and in 8 patients in the placebo group (ns) .After the intervention, clinical parameters (weight, height) and biochemical parameters (liver enzymes activity, the level of total and conjugated bilirubin, total protein and albumins, vitamin A and E) were similar both in the LGG and placebo groups. The level of Alpha-1 Antitrypsin (A1AT) concentration in stools was within normal limits. Also, the statistical differences between groups were not revealed.The gut microbiota and gut microbiota metabolisms of both groups measured with the use of SCFA did not differ after 6 months.

Conclusion: The LGG supplementation after the Kasai portoenterostomy in children suffering from the bile duct obstruction in the pilot study did not significantly influence the incidence of ascending cholangitis, the course of cholestatic liver disease, the death risk and the liver transplantation necessity.The LGG supplementation did not significantly influence gut microbiota and its metabolism.

Disclosure of Interest: None declared

P0698 PEDIATRIC PANCREATITIS. MULTICENTRE PROSPECTIVE DATA COLLECTION AND ANALYSIS BY THE HUNGARIAN PANCREATIC STUDY GROUP

A. Párniczky¹, N. Lásztity¹, on behalf of Hungarian Pancreatic Study Group, D. Mosztbacher², A. Tóth³, D. Szűcs⁴, N. Vass⁵, J. Czelecz⁶, C. Andorka⁷, G. Veres⁸, I. Guthy⁹, R. Szmola¹⁰, B. Németh¹¹, A. Balázs¹², M. Sahin-Tóth¹³, P. Hegyi¹⁴, on behalf of Hungarian Pancreatic Study Group

¹Heim Pál Children's Hospital, Budapest, ²Department of Pediatrics, János Balassa County Hospital,, Szekszárd, ³Department of Pediatrics and Pediatric Health Center, University of Szeged, Faculty of Medicine, ⁴Department of Pediatrics and Pediatric Health Center, ⁵Department of Pediatrics and Pediatric Health Care, University of Szeged, Faculty of Medicine, Szeged, ⁶4 Bethesda Children’s Hospital, ⁷Department of Pediatrics and Pediatric Health Center, Semmelweis University, First, ⁸Department of Pediatrics and Pediatric Health Center, Semmelweis University, Budapest, ⁹Szabolcs-Szatmár-Bereg County Hospitals, Jósa András University Teaching Hospital, Nyíregyháza, ¹⁰Department of Interventional Gastroenterology,, National Institute of Oncology, Budapest, ¹¹ First Department of Medicine, University of Szeged, Faculty of Medicine, ¹² First Department of Medicine, University of Szeged, Faculty of Medicine, Szeged, Hungary, ¹³Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, United States, ¹⁴University of Szeged, First Department of Medicine,, Hungarian Academy of Sciences - University of Szeged, Monument, Szeged, Hungary

Contact E-mail Address: andrea.parniczky@gmail.com

Introduction: The incidence of pediatric pancreatitis (PP) has increased in the last decade. Some of the recent studies showed that the occurrence of the disease has grown over 10/100,000 which is not much less than in adults. We have established the Paediatric Section of the Hungarian Pancreatic Study Group in order to organize nationwide data collection and improve themanagement of the disease.

Aims & Methods: Our aim was to analyse the epidemiology, risk factors, management and clinical outcome of PP in Hungary. 56 children suffering from PP were enrolled from 7 centres between 2012 and 2014.

Results: 61% of the children were female. 31 acute (AP), 11 recurrent acute (RAP) and 14 chronic pancreatitis (CP) cases were recorded in the registry. 84% of the AP patients had mild and 16% moderate episodes, however, no severe AP was observed. In RAP patients pancreatitis seemed to be more severe than in patients having isolated episodes (mild: 73% moderate: 18%, severe: 9%). Mortality was not observed at all. Without genetic testing we could identify the etiological factors only in 44% of the cases, the others remained idiopathic. In 17 cases, genetic analyses of PRSS1, SPINK1, CFTR and CTRC genes have been completed. Genetic alterations in PRSS1 were found in 3 cases (all CP), in SPINK1 in 4 cases (1 RAP and 3 CP), in CFTR in 1 case (CP) and in CTRC in 10 cases (3 AP and 7 CP). In 5 CP patients mutations in two genes were observed (3 SPINK1-CTRC, 1 PRSS1-SPINK, 1 CFTR-CTRC).

Conclusion: Genetic testing is essential to identify the etiological factors in children with pancreatitis.

Disclosure of Interest: None declared

P0699 RESULTS OF A PROSPECTIVE CLINICAL TRIAL IN PEDIATRIC PANCREATITIS (PINEAPPLE - PAIN IN EARLY PHASE OF PEDIATRIC PANCREATITIS)

D. Mosztbacher¹, A. Tóth², A. Párniczky³, F. Zsoldos³, V. Ila⁴, A. Szentesi⁵, G. Tóth¹, C. Bereczki², Z. Bognár³, P. Hegyi⁵, on behalf of HPSG

¹Department of Pediatrics, János Balassa County Hospital, Szekszárd, ²Department of Pediatrics and Pediatric Health Center, University of Szeged, Faculty of Medicine, Szeged, ³Heim Pál Children's Hospital, Budapest, ⁴Department of Pediatrics, Dr. Kenessey Albert Hospital, Balassagyarmat, ⁵First Department of Internal Medicine, University of Szeged, Faculty of Medicine, Szeged, Hungary

Contact E-mail Address: dora.mosztbacher@gmail.com

Introduction: The documented incidence of pediatric pancreatitis (PP) is very low, less than 1/100,000 in almost all European countries, whereas it is around 3.6-13.2 in the USA and Australia. Moreover, there are unexpectedly large differences between the incidences of PP among the countries and hospitals in Europe.

Aims & Methods: The aim of the PINEAPPLE study (ISRCTN35618458) is to understand the current practice of diagnosis of PP and to develop EBM guidelines that helps to evaluate (in a reliable and cost efficient way) the necessity of pancreatic enzyme measurement (PEM) and abdominal ultrasonography when a child has abdominal pain.

PINEAPPLE is a registered, multinational observational clinical trial. The PINEAPPLE-R subtrial is a retrospective review on children (patients under 18) records appearing at ER units, whereas, the PINEAPPLE-P subtrial is a prospective part of the study where detailed patients data (concerning medical history, complaints, symptoms, physical examination) are collected and PEM and abdominal imaging are performed in all cases. Until now 6012 patients records/PINEAPPLE-R and 90 patients/PINEAPPLE-P were enrolled from five pediatric centres.

Results: PINEAPPLE-R: 12% (710/6012) of the patients appearing at ER unit had abdominal pain. Only 2,5% (18/710) of them had PEM, whereas 30% (213/710) had transabdominal ultrasonograpy. Pancreatitis was diagnosed in one case only. PINEAPPLE-P: 1 pancreatitis of 90 patients with abdominal pain was diagnosed.

Conclusion: The PINEAPPLE-R study clearly shows that the number of PEM performed at ER units are unacceptably low in children, which could be the reason of low incidences of PP. More patients are crucially needed for PINEAPPLE-P in order to develop EBM guidelines.

Disclosure of Interest: None declared

TUESDAY, OCTOBER 27, 2015   09:00-17:00

PANCREAS II – HALL 7__________

P0700 IMPACT OF UPSIZING PERCUTANEOUS CATHETERS IN PATIENTS WITH SUSPECTED INFECTED NECROTIZING PANCREATITIS

J. Van Grinsven¹, P. Timmerman², K. P. van Lienden³, J. W. Haveman², D. Boerma⁴, C. H. van Eijck⁵, P. Fockens⁶, H. C. van Santvoort¹, M. A. Boermeester¹, M. G. Besselink¹, on behalf of the Dutch Pancreatitis Study Group

¹Surgery, Academic Medical Center Amsterdam, Amsterdam, ²Surgery, University Medical Center Groningen, Groningen, ³Radiology, Academic Medical Center Amsterdam, Amsterdam, ⁴Surgery, St. Antonius Hospital, Nieuwegein, ⁵Surgery, Erasmus Medical Center, Rotterdam, ⁶Gastroenterology and Hepatology, Academic Medical Center Amsterdam, Amsterdam, Netherlands

Contact E-mail Address: j.vangrinsven@pancreatitis.nl

Introduction: Infected necrotizing pancreatitis is nearly always an indication for invasive treatment. Percutaneous catheter drainage (PCD) is now well established as the first intervention in a ‘step-up approach’. It has been suggested that a drain upsizing strategy might obviate the need for additional surgical necrosectomy and improve clinical outcome, but studies on this topic are lacking.

Aims & Methods: We retrospectively identified patients with necrotizing pancreatitis from in-hospital databases (2004-2014) in four tertiary referral centers. Patients who underwent PCD as primary treatment for suspected infected necrosis were included. We compared patients’ outcomes of a single center that attempted to routinely upsize in case of lack of clinical improvement with those of patients treated in the three centers where this strategy was not used routinely. Primary outcome was the need for additional surgical necrosectomy following PCD. Secondly, we compared complications including mortality and new onset (multi) organ failure.

Results: Of 1427 consecutive patients with acute pancreatitis, 369 patients (26%) were diagnosed with necrotizing pancreatitis, of which 117 patients (32%) underwent primary PCD for suspected infected necrosis. Infected necrosis was ultimately proven in 82 of these patients (70%). In total 42 patients (36%) were treated in the drain upsizing strategy center versus 75 patients (64%) in the non-upsizing strategy centers. Patient characteristics were similar in baseline, except for differences in age and timing of first PCD for which we corrected in the analyses. The median of drain procedures was 3 (interquartile range (IQR) 2-4) in the upsizing strategy center versus 2 (IQR 1-2) in the non-upsizing strategy centers, P<.001. The maximal drain size was median 16 French (IQR 14-20) compared to 14 French (IQR 12-14), P<.001, respectively. Additional surgical necrosectomy was required in significantly less patients in the upsizing strategy center, 29% vs. 52% P=.045. Mortality was comparable in both groups, 17% vs. 19%, P=0.79. New onset (multi) organ failure after PCD occurred in 5% of patients in the upsizing strategy center compared to 20% of patients in the non-upsizing strategy centers, P=0.11.

Conclusion: A PCD upsizing strategy for patients with suspected infected necrotizing pancreatitis appears to reduce the need for surgical necrosectomy. Future studies will have to demonstrate the true clinical value of PCD upsizing and whether this should be performed on indication or preemptively.

Disclosure of Interest: None declared

P0701 ELEVATED LEVELS OF IL-6 AND IL-8 PREDICT DEVELOPMENT OF RESPIRATORY FAILURE IN PATIENTS WITH ACUTE PANCREATITIS

J. Samanta¹, S. Singh², R. Prasada¹, N. Dhaka¹, S. K. Arora², A. N. Aggarwal³, V. Gupta⁴, S. K. Sinha¹, R. Kochhar¹

¹Gastroenterology, ²Immunopathology, ³Pulmonary medicine, ⁴Surgery, Postgraduate Institute of Medical Education and Reserch, Chandigarh, India., Chandigarh, India

Contact E-mail Address: dj_samanta@yahoo.co.in

Introduction: Acute lung injury (ALI) is the commonest organ failure in patients with acute pancreatitis (AP). It is a major cause of early mortality in such patients and cytokines play a major role in its pathophysiology.

Aims & Methods: Aim & Methods: To study the predictive role of inflammatory cytokines in development of ALI in patients with AP.

In this prospective study between July 2013 and December 2014 consecutive eligible patients of AP underwent complete demographic, clinical, biochemical and radiological evaluation. Severity classification was done using revised Atlanta classification and also systemic inflammatory response score (SIRS) and Bedside Index of Severity of Acute Pancreatitis(BISAP), CT Severity Index (CTSI) and APACHE II scores were used. Serial arterial blood gas (ABG) analyses were done and ALI severity defined as per Berlin Classification using PaO₂/FiO₂ ratio. Development of ALI was monitored in all the patients. Serum levels of interleukin (IL)-6, IL-8, IL-10, IL-1b and TNFa were measured at baseline (day 1) for all patients and on day 3 in those who had ALI. For comparative analysis patients were divided into 2 groups: with and without ALI. The ALI cohort was further subdivided into persistent ALI (P-ALI) and transient ALI (T-ALI). A subgroup of ALI patients who developed ALI later during hospital stay was defined as “late onset” ALI (LO-ALI) to devise a predictive model for ALI using cytokine levels. Statistical analysis was done using SPSSv22.0

Results: Of the 107 patients (mean age of 38.4 yrs, 64.5% males, etiology: alcohol 36.4% gallstone disease 26.2% and others 51.4%), ALI developed in 51 (47.7%) of whom 40(78.4%) had ALI on admission while 11(21.6%) had LO-ALI. T-ALI was seen in 16(31.4%) while 35 (68.6%) had P-ALI. Patients with ALI had significantly higher IL-1b (p < 0.0001), IL-6 (p < 0.0001), IL-8 (P < 0.001) and TNFa (P < 0.0001) and lower IL-10 (p < 0.0001) levels on day 1, when compared to non-ALI group. In the ALI group, day 3 levels of IL-1b (p=0.001), IL-6 (p=0.02), IL-8 (p=0.006) and TNFa (p=0.006) were significantly higher than day 1 levels. Significant rise on day 3 of only IL-1b (p=0.04) was observed in T-ALI group as compared to both IL-1b (p=0.001) and TNFa (p=0.02) in the P-ALI group. Day 1 levels of IL-6 and IL-8 had strong positive correlation with severity indices such as SIRS (p < 0.001), BISAP (p < 0.001) and CTSI (p < 0.0001) as also with outcome measures such as need for intervention (p < 0.0001), hospital stay (p < 0.0001) and intensive care stay (p < 0.0001). LO-ALI group had significantly higher levels of IL-6 (p < 0.0001), IL-8 (p < 0.0001), TNFα (p < 0.0001) and IL-1β (p < 0.006). IL-6 at cut off levels of 84.85 pg/mL (AUC=0.94, sensitivity & specificity 91%) and IL-8 at cut off level of 112.5 pg/mL (AUC=0.909, sensitivity 91% specificity 94.6%) predicted subsequent development of ALI.

Conclusion: Rising levels of IL-1b and TNFα suggest development of persistent ALI. IL-6 and IL-8 levels at admission can predict the future development of late onset ALI.

Disclosure of Interest: None declared

P0702 STUDY OF LUNG FUNCTION TESTS TO PREDICT DEVELOPMENT OF ACUTE LUNG INJURY IN PATIENTS WITH ACUTE PANCREATITIS

J. Samanta¹, R. Prasada¹, N. Dhaka¹, S. K. Arora², A. N. Aggarwal³, V. Gupta⁴, S. K. Sinha¹, R. Kochhar¹

¹Gastroenterology, Postgraduate Institute of Medical Education and Reserch, ²Immunopathology, Postgraduate Institute of Medical Education and Reserch, Chandigarh, India., ³Pulmonary Medicine, ⁴Surgery, Postgraduate Institute of Medical Education and Reserch, Chandigarh, India

Contact E-mail Address: dj_samanta@yahoo.co.in

Introduction: The commonest organ failure in patients with acute pancreatitis (AP) is acute lung injury (ALI). Data on pulmonary function tests (PFT) in AP is limited.

Aims & Methods: To study PFT in patients with AP and evaluate the role of PFTs in predicting ALI.

In this prospective study between July 2013 and December 2014 consecutive patients of AP underwent complete demographic, clinical, biochemical and radiological evaluation. Severity classification was done using revised Atlanta classification and also systemic inflammatory response score (SIRS) and Bedside Index of Severity of Acute Pancreatitis (BISAP), CT Severity Index (CTSI) and APACHE II scores were used. Serial arterial blood gas (ABG) analyses were done and ALI severity defined as per Berlin classification using PaO₂/FiO₂ ratio. Development of ALI was monitored in all the patients. PFTs were done by spirometry as soon as possible after admission. Forced expiratory volume in first second (FEV₁), forced vital capacity (FVC) and FEV₁/FVC ratio were used as basic parameters for interpretation and all measurements were expressed as a percentage of their predicted values (FVC%, FEV₁%). Patients were divided into 2 groups: with and without ALI. The ALI cohort was further subdivided into persistent ALI (P-ALI) and transient ALI (T-ALI). A subgroup of ALI group which developed ALI later during hospital stay was defined as “later onset” ALI (LO-ALI) to devise a predictive model for ALI with PFT parameters. Statistical analysis was done using SPSSv22.0

Results: Of the 107 patients (mean age of 38.4 yrs, 64.5% males, etiology: alcohol 36.4% gallstone disease 26.2% and others 51.4%), ALI developed in 51 (47.7%) patients of whom 40 (78.4%) had ALI on admission while 11 (21.6%) had LO-ALI. T-ALI was seen in 16 (31.4%) while 35 (68.6%) had P-ALI. PFT could be performed in 87 patients (52 non-ALI, 35 ALI including 9 from LO-ALI subgroup). ALI group had significantly lower FVC% (p < 0.0001) and FEV₁% (p < 0.0001) signifying higher lung dysfunction compared to those without ALI. Similarly, P-ALI had lower FVC% (58.9 ± 14.8 vs. 69.6 ± 17.2, p=0.06) and lower FEV₁% (p=0.04) than T-ALI. A significant correlation existed between PaO₂/FiO₂ ratio and FVC% (r=0.513, P < 0.0001) and FEV₁% (r=0.488, p < 0.0001). Both FEV₁% and FVC% showed significant correlation with other severity parameters such as SIRS (p < 0.0001), BISAP (p < 0.00011), CTSI (p < 0.0001) and APACHE II (p < 0.002) and also with need for intervention (p=0.04), hospital stay (p < 0.0001) and intensive care stay (p=0.001). LO-ALI (9) had significantly lower FVC% (p=0.02) and FEV₁% (p=0.03) as compared to those without ALI, but a predictive cut off could not be achieved (AUC=0.257, p=0.021) due to small numbers.

Conclusion: Patients who eventually develop ALI later have more severe lung dysfunction at baseline than those who do not and PFTs can act as a tool to predict it.

Disclosure of Interest: None declared

P0703 USE OF A NEW PLASTIC PANCREATIC STENT TO FACILITATE BILIARY CANNULATION IN DIFFICULT ERCP

J. García-Cano¹, M. A. Godoy-López², L. Taberna-Arana³

¹Department of Digestive Diseases, ²Department of Radiology, Hospital Virgen de la Luz, ³Family Practice, District Health of Cuenca, Cuenca, Spain

Contact E-mail Address: jgcl7@live.com

Introduction: Use of a pancreatic stent (PS) to facilitate biliary cannulation is one of the so called pancreatic techniques in which the pancreas serve as a step to gain the Common Bile Duct (CBD). We report on the performance characteristics of using a new plastic PS to facilitate CBD cannulation in difficult ERCP.

Aims & Methods: CBD cannulation was attempted with a sphincterotome loaded with a guidewire controlled by the endoscopist. In cases of difficult biliary access in which the Pancreatic Duct was cannulated, an straight Advanix PS (Boston Scientific), having 5 french, and 4 cm in length without inner barbs was placed. This PS has a proximal radiopaque marker that facilitates recognition of the indwelling position. After this, physician-controlled guidewire was attempted by using the PS to direct the sphincterotome into the CBD.

Results: Among 98 ERCPs in patients with naïve Papilla, 16 (16.3%) received an Advanix PS to facilitate biliary cannulation. Successful cannulation was achieved in 16 (100%) without the need of Needle-Knife-Precut. In one patient the PS dislodged from the Papilla during cannulation attempts. No postERCP pancreatitis was observed. There were eight patients with CBD stones, three with pancreatic head cancer and five with type I sphincter of Oddi dysfunction after cholecistectomy. On radiological follow-up, 7/15 (47%) PS had spontaneouly passed after two weeks, whereas 8/15 (53%) remained still in place and had to be removed by gastroscopy. No pancreatitis occurred after removal.

Conclusion: Endoscopist-controlled guidewire over this new PS facilitates biliary cannulation and appears to prevent from postERCP pancreatitis. The PS althougth has no inner barbs, remained in place for more than two weeks in half of the patients and had to be removed by gastroscopy. The inner radiopaque marker results very useful to know its position.

Disclosure of Interest: None declared

P0704 GHRELIN MOLECULAR SYSTEM IN THE PROTECTION OF PANCREATIC ACINAR CELLS

J. Bonior¹, J. Jaworek¹, M. Kot¹, P. Pierzchalski¹

¹Department of Medical Physiology, Faculty of Health Sciences, Jagiellonian University Medical College, Krakow, Poland

Contact E-mail Address: joanna.bonior@uj.edu.pl

Introduction: Ghrelin (GHRL), an endogenous ligand for the growth hormone (GH) secretagogue receptor (GHS-R) has been isolated from the stomach and identified in the pancreas. GHRL has been demonstrated to protect pancreatic tissue from caerulein-induced acute pancreatitis (CIP).

Aims & Methods: To investigate the effect of GHRL and caerulein on gene expressions and on protein signals of GHRL, GHS-R1 and of an antioxidant enzyme: superoxide dysmutase (SOD) in the isolated pancreatic acini.

Pancreatic acini were isolated by collagenase digestion from control rats and from rats pretreated with GHRL (50,0 μg/kg i. p.) administered 48 hours before the isolation. Isolated acini were incubated with high concentration of caerulein (10^–8M). The gene expressions were determined by RT-PCR, whereas the protein contents were assessed employing Western-blot.

Results: Protein expressions and mRNA signals for GHS-R1a receptor, GHRL and for SOD-3 have been detected in the pancreatic acini under basal conditions and have been significantly upregulated following application of GHRL to the rats. Incubation with caerulein markedly downregulated signals of GHS-R1a and SOD-3 in pancreatic acini, but failed to affect these for GHRL. Pretreatment of rats with GHRL prevented caerulin-induced suppression of GHS-R1a and SOD-3 signals.

Conclusion: Caerulein overstimulation is able to modify the GHS-R1a receptor in the pancreatic acini and this effect could be prevented by pretreatment of rats with GHRL. Protective effect of GHRL on caerulein-induced pancreatitis could be dependent, at least in part, on the activation of SOD and improvement of antioxidant system in the pancreas.

Disclosure of Interest: None declared

P0705 ENDOSONOGRAPHY-GUIDED NECROSECTOMY VERSUS SURGICAL TREATMENT OF INFECTED WALLED-OFF PANCREATIC NECROSIS: A COMPARATIVE STUDY

J. C. Ardengh¹², E. Taglieri², O. Micelli-Neto², D. C. Aragon³, R. Kemp¹, J. S. dos-Santos¹

¹Surgery and Anatomy of HCFMRP-USP, HCFMRP-USP, Ribeirão Preto, ²Endoscopy Departament, Hospital 9 de Julho, São Paulo, ³Estatistical Department, HCFMRP-USP, Ribeirão Preto, Brazil

Contact E-mail Address: jcelso@uol.com.br

Introduction: The surgical necrosectomy (SUR-N) of walled-off pancreatic necrosis (WOPN) has high morbidity and mortality rates. The new options of treatments have been increasingly used such as step-up approach and endoscopic drainage. The endoscopic approach is not yet defined as a first option for this treatment, but have been increasingly used for its efficacy, safety and the possibility of necrosis approach in any situation with the aid of endoscopic ultrasonography (EUS).

Aims & Methods: The objective was to study and compare the characteristics, clinical course, the immediate and late adverse events in patients with WOPN treated by SUR-N and EUS-guided necrosectomy (EUS-N). 63 patients with WOPN were treated by SUR-N (35) and EUS-N (28) from Aug/90 to Jul/2014.

Results: The mean age was higher in the EUS-N (p <0.01). Sex, ASA index, diabetes, obesity, and cardiovascular risk factor before treatment were similar to the SUR-N and EUS-N groups (p> 0.05). Cause of AP (p=0.06), infected necrosis (p=0.13) and median time from onset of symptoms to treatment (p=0.34) were similar for both groups. The Marshal (p < 0.01) and CT Balthazar score (p < 0.01) were significantly higher for SUR-N. Acute adverse events were statistically significant for the EUS-N vs SUR-N (71% vs 37%, p < 0.01). Despite the occurrence only in SUR-N group of sepsis, post-operative hernia, bowell obstruction, pneumonia, fistula (pancreatic and biliary) and chylous ascites there was no statistical difference compared to EUS-N group. The late adverse events were statistically significant for patients undergoing SUR-N vs EUS-N in relation to bowell and biliary obstruction (21% vs 0%, p=0.04 and 27% vs 0%, p = 0.01, respectively) and required surgery (36% vs. 8%, p=0.02, respectively). The average follow-up was 493 days, there was no difference between patients who underwent SUR-N and EUS-N in relation to pancreatic sequelae, including pseudocyst (p = 0.62), cases of onset diabetes (p=0.31) or need for pancreatic enzymes (p=0.29).

Conclusion: Compared to SUR-N, the EUS-N showed a lower rate of adverse events. EUS-N appears to be a safe and effective procedure must be included in the therapeutic algorithm patients with WOPN.

Disclosure of Interest: None declared

P0706 ETHANOL AND ETHANOL METABOLITES DECREASE THE ACTIVITY AND EXPRESSION OF CFTR CL- CHANNEL AND IMPAIR EXOCRINE PANCREATIC FLUID AND BICARBONATE SECRETION

J. Maléth¹, A. Balázs¹, Z. Balla¹, B. Kui¹, P. Palagi¹, M. Katona¹, T. Madácsy¹, L. Judák¹, I. Németh², L. Kemény¹, Z. Rakonczay¹, V. Venglovecz³, I. Földesi⁴, Á. Somorácz⁵, K. Borka⁵, D. Perdomo⁶, G. Lukács⁶, M. Gray⁷, M. Sendler⁸, J. Mayerle⁸, J.-P. Kühn⁸, M. M. Lerch⁸, M. Sahin-Tóth⁹, P. Hegyi¹

¹First Dept. of Medicine, ²Department of Dermatology and Allergology, ³Department of Pharmacology and Pharmacotherapy, ⁴University of Szeged, Szeged, ⁵Semmelweis University, Budapest, Hungary, ⁶McGill University, Motreál, Canada, ⁷Newcastle University, Newcastle upon Tyne, United Kingdom, ⁸University Medicine Greifswald, Greifswald, Germany, ⁹Boston University Henry M. Goldman School of Dental Medicine, Boston, United States

Contact E-mail Address: jozsefmaleth1@gmail.com

Introduction: Excessive ethanol consumption is one of the most common causes of acute and chronic pancreatitis. It is also documented that genetic defects of CFTR can lead to pancreatitis, however the effects of alcohol consumption on CFTR function in the pancreas is not known.

Aims & Methods: Our aim was to investigate the effects of ethanol and ethanol metabolites on the exocrine pancreatic fluid and bicarbonate secretion and on CFTR function and expression. Intra/interlobular pancreatic ducts were isolated from guinea pigs to study the effects of ethanol and ethanol metabolites on the in vitro pancreatic fluid and bicarbonate secretion. In vivo exocrine pancreatic secretion of anesthetized mice has been investigated using magnetic resonance cholangiopancreaticography (MRCP). The effects of ethanol and ethanol metabolites on CFTR activity pancreatic ductal epithelial cells (PDEC) was measured by patch clamp. CFTR expression in human tissue samples were assessed by immunohistochemistry in control human pancreatic tissue and in acute and chronic alcohol-induced pancreatitis. The mechanism of the decreased CFTR expression has been characterized in MDCK cell by western blot, cell surface elisa and pulse chase experiments.

Results: The administration of 100mM ethanol, or the non-oxidative ethanol metabolite palmitoleic acid (POA; 200µM) markedly reduced the in vitro fluid and bicarbonate secretion of isolated guinea pig pancreatic ducts. Moreover MRCP showed that the total excreted volume (used as a marker of the in vivo pancreatic fluid secretion) was significantly decreased after the i.p. injection of 1.75g/kg ethanol and 750mg/kg palmitic acid (PA). Exposure of guinea pig PDEC to 100mM ethanol or 200µM POA significantly decreased the forskolin-stimulated CFTR currents. Next we evaluated the effect of ethanol on the CFTR expression. Using human tissue samples we showed that CFTR expression was significantly decreased in acute or chronic alcohol-induced pancreatitis both at mRNA and protein levels. Similar decrease of pancreatic ductal CFTR expression has been observed in guinea pigs after the i.p. injection of 1.75g/kg ethanol and 750mg/kg PA. Experiments on MDCK-II cell expressing WT human CFTR revealed that ethanol and its metabolites decrease CFTR expression and plasma membrane density via accelerated channel plasma membrane turn over and damaged protein folding.

Conclusion: The findings indicate that alcohol and alcohol metabolites induce a loss of CFTR function and expression, which in turn impairs pancreatic ductal fluid and bicarbonate secretion. We suggest that the correction of CFTR function and expression should offer therapeutic benefit.

Disclosure of Interest: None declared

P0708 EXTENT OF NECROSIS AS KEY DETERMINANT OF OUTCOME IN PATIENTS WITH ACUTE NECROTIZING PANCREATITIS

N. Dhaka¹, J. Samanta¹, P. Gupta², V. Gupta³, S. K. Sinha¹, R. Kochhar¹

¹Gastroenterology, Postgraduate Institute of Medical Education and Reserch, ²Radiodiagnosis, ³Surgery, Postgraduate Institute of Medical Education and Reserch, Chandigarh, India

Contact E-mail Address: dhakanaren@gmail.com

Introduction: Necrosis in patients of pancreatitis can be either pancreatic, peripancreatic or both. However the impact of site of necrosis over collection location and disease outcome is still unknown.

Aims & Methods: To evaluate the impact of site of necrosis upon location of collections and outcome in patients of Acute Necrotizing Pancreatitis (ANP).

161 Patients with ANP (Mean age-39.91 ± 13.78 yrs) were classified according to the site of necrosis [Pancreatic (Group I), Peripancreatic (Group II) or both (Group III)]. They were managed as per institute protocol (Step up), followed up for development of fluid collections and then categorized according to locations of collections within the abdominal cavity [Pancreatic (A), Peripancreatic (B), both (C), Peripancreatic with distant (D) and at all sites (E)]. Outcome variables were hospital stay, ICU stay, need for pigtail drainage, surgery and mortality. Data was recorded in excel sheet and statistical analysis was done using SPSS v17.0.

Results: Type III necrosis was the commonest type of necrosis (n=69, 42.8%), followed by type II (n=46, 28.57%) and type I necrosis (n=46, 28.57%). Type I necrosis was significantly associated with collection location C [32(82.6%)], whereas type II necrosis had significant association with location D [20(43.47)] and Type III necrosis had association with location E [59(85.5%)] (p < 0.001). Surgery, mortality and need for percutaneous drainage were exclusively seen in type III necrosis [7(10.14%), 14(20.28%), 54(78.26%)]. Duration of hospital and ICU stay were significantly associated with type III compared to type I necrosis (34.28 ± 24.88 vs. 13.26 ± 7.46 days, 8.17 ± 12.96 vs. 0.89 ± 2.72 days, p < 0.001).

Conclusion: Collections develop in a compartment more than the area of necrosis. Outcome of patients with necrosis involving both pancreas and peripancreatic region is worst followed by only peripancreatic necrosis and pancreatic necrosis alone in sequence.

Disclosure of Interest: None declared

P0709 COFILIN-1-MEDIATED GROWTH REGULATION IN PANCREATIC CANCER CELLS IS ASSOCIATED WITH DOWNREGULATION OF GLI1 AND INCREASED ACTIVITY OF THE MAL/SRF TRANSCRIPTION FACTOR COMPLEX

B. P. Kaistha¹, S. Kirchhoff¹, H. Schmidt¹, M. Lauth², R. Singh², B. Sipos³, T. Gress¹, M. Buchholz¹

¹Klinik für Innere Medizin, SP Gastroenterologie, ²Institute of Molecular Biology and Tumor Research (IMT), Philipps-Universität Marburg, Marburg, ³Institut für Allgemeine Pathologie, Universitätsklinikum Tübingen, Tübingen, Germany

Contact E-mail Address: malte.buchholz@staff.uni-marburg.de

Introduction: We have previously described a multi-step high-content screening approach to identify novel functionally relevant target genes in pancreatic ductal adenocarcinoma (Buchholz et al. 2015, PLoS-One, 10:e0122946). The results of these analyses predicted an unexpected and previously undocumented role for the small actin-binding protein cofilin-1 in growth control of pancreatic cancer cells.

Aims & Methods: Multiple tissue arrays, RNAi, cell proliferation and viability assays, FACS analysis, Western blot, inducible shRNA clones, reporter gene assays.

Results: Cofilin-1 is strongly overexpressed in human pancreatic ductal adenocarcinoma both at the mRNA and at the protein level. RNAi-mediated knockdown of cofilin-1 gene expression in four different pancreatic cancer cell lines resulted in significantly reduced cell viability and proliferation rates, while apoptosis was not induced. Further, the capacity for anchorage-independent growth was strongly reduced in the absence of cofilin-1 expression. Moreover, stable repression of cofilin-1 expression in pancreatic cancer cell clones significantly decreased the growth of xenograft tumors in vivo. Flow cytometric analyses indicated that these effects were primarily mediated by attenuation of G1/S transition during cell cycle. Mechanistically, CFL1 knockdown resulted in simultaneous overactivation of the MAL/SRF transcription factor complex and downregulation of expression of the Hedgehog pathway effector Gli1, which is well known to regulate pancreatic cancer cell growth.

Conclusion: In addition to its previously known roles in actin dynamics and cell motility, cofilin-1 has a direct and essential role in growth regulation of pancreatic cancer cells. The clinical significance of this observation is emphasised by the strong and widespread overexpression of cofilin-1 in human PDAC.

Disclosure of Interest: None declared

P0710 A FAST ASSAY TO GAUGE FOR TAA-REACTIVE T-CELLS IN PBMCS FROM PATIENTS WITH PANCREATIC CANCER

E. Rangelova¹², Q. Meng³, L. Zhiang³, T. Poiret³, C. Verbeke⁴, E. Dodoo⁵, R. Segersvärd¹², M. Del Chiaro¹², M. Maeurer³

¹Division of Surgery, Karolinska University Hospital, ²CLINTEC, ³Therapeutic Immunology, Karolinska Institute, ⁴Division of pathology, ⁵Department of neurosurgery, Karolinska University Hospital, Stockholm, Sweden

Contact E-mail Address: elena.rangelova@ki.se

Introduction: Active cellular therapy (ACT) using ex-vivo expanded T-cells from patients with cancer, obtained by apheresis, can represent a viable source for anti-cancer directed cellular therapy. The objective was to establishe a T-cell expansion protocol using two rounds of re-stimulation with TAA peptides along with IL-2, IL-15 and IL-21. In order to gauge the ex-vivo cellular reactivity as well as the potential to successful expand antigen-specific T-cells from patients with pancreatic cancer, a screening assay using whole-heparin blood, to gauge for TAA reactivity (NY-ESO-1, survivin, mesothelin) and control antigens (EBNA-1, EBNA-3, CMVpp65) was established.

Aims & Methods: Fresh blood samples were obtained from 24 patients with pancreatic cancer and from 6 individuals with pre-malignant lesions and tested for anti-TAA reactivity defined by CD3 + CD4+/CD3 + CD8+ T-cell proliferation and IFN- γ production. T-cells were expanded without cytokines, with IL-2 and IL-7, or with IL-2, IL-15 and IL-21. For T-cell expansion, PBMCs were expanded by adding cytokine and TAA peptides. CD3, CD4, CD8, CD45RA and CCR7 were determined by flow cytometry and TAA-reactive T-cells were identified by ICS (IL-2, TNF, IFN and IL-17).

Results: IFN-γ responses were detected in 90% (27 of 30) in blood samples for mesothelin, 55.3% (16 of 30) for survivin and 43.3% (13 of 30) for NY-ESO-1 (without adding cytokines). Cellular responses could be augmented by adding cytokines, i.e. IL-2 and IL-7 (to favor CD4+ T cell proliferation) or IL-2, IL-15 and IL-21 (to favor CD8+ T cell proliferation). IFN-γ responses were detecetd in 100% (30 of 30) in blood samples for EBNA1, 100% (30 of 30) for EBNA3 and 93.3% (28 of 30) for CMV without the addition of cytokines and the cellular responses could be augmented by adding cytokines. TAA-reactive T cells could be successfully expanded ex vivo and exhibited TAA-specific production of IFN-γ and TNF-α and a CD8 + CD45RA-CCR7+ phenotype.

Conclusion: A TAA-specific whole blood assay can be used to gauge the potential for expansion of TAA-reactive T-cells in peripheral blood from patients with pancreatic cancer. TAA-reactive T-cells can be successfully expanded in IL-2, IL-15 and IL-21 and could represent a viable source for the cellular therapy of patients with pancreatic cancer.

Disclosure of Interest: None declared

P0711 GENERATION OF TUMOR-INFILTRATING LYMPHOCYTE CULTURES FROM PANCREATIC CANCER FOR ADOPTIVE TRANSFER THERAPY

E. Rangelova¹², Q. Meng³, L. Zhiang⁴, T. Poiret⁴, C. Verbeke⁵, E. Dodoo⁶, R. Segersvärd¹², M. Del Chiaro¹², M. Maeurer⁴

¹Division of Surgery, Karolinska University Hospital, ²CLINTEC, ³Karolinska Institute, Stockholm, Sweden, ⁴Therapeutic Immunology, Karolinska Institute, ⁵Division of Pathology, ⁶Department of neurosurgery, Karolinska University Hospital, Stockholm, Sweden

Contact E-mail Address: elena.rangelova@ki.se

Introduction: The generation of T-lymphocyte cultures with specific reactivity against autologous tumor is a prerequisite for effective adoptive transfer therapies – among the most successful of immune therapies. Pancreatic cancer-specific tumor-infiltrating lymphocyte (TIL) cultures are difficult to obtain, but can represent a viable T-cell source for cellular therapy of patients with pancreatic cancer. The objective was to optimize the method for generation of T-lymphocyte cultures from pancreatic cancer TILs.

Aims & Methods: Pancreatic cancer tissue was obtained by excision or core biopsy from the fresh surgical specimens of 30 patients and cultured for 10 days with cytokines (IL-2, IL-15, and IL-21). TILs were extracted and expanded using OKT-3 and irradiated allogenic peripheral blood mononuclear cells. The specific activity of TILs for recognition of tumor-associated antigens (mesothelin, survivin, and NY-ESO-1) was evaluated by IFN-γ production and intracellular cytokine production and detected by ELISA and ICS. Clonal T-cell populations were tested by a panel of TCR Vβ-specific antibodies and by TCR CDR3 PCR-guided analysis, along with T-cell differentiation and exhaustion markers by flow cytometry.

Results: TILs from all 30 patients, up to 10e11 cells, could successfully be expanded using the combination of IL-2/15/21. Even the core biopsy specimens yielded at least 1.5 x 10e9 CD8 + TILs. Four-week TIL-cultures showed up to 90% CD8 + T-cells, yet one culture exhibited exclusively CD4 + TILs with a CD45RA-CCR7+ phenotype. The majority of the CD8+ and CD4+ TILs resided in the central memory and effector memory subsets (CCR7 + CD45RA- and CCR7-CD45RA-). Some TIL cultures showed preferential expression of TCR-Vβ families - in CD8 + TILs 99.3% in Vβ13.2, 77% in Vβ1, 68.7% in Vβ22, 64% in Vβ14 for individual patients. 30% of the expanded Vβ families were monoclonal. ICS analysis showed a low frequency (up to 2.5%) of mesothelin, survivin or NY-ESO-1 reactive CD8 + TILs. TILs from one patient showed up to 15% NY-ESO-1 specific IFN-γ and TNF-α production in CD4+ and CD8 + TILs. Specific T-cell killing of autologous tumor cells could be demonstrated by chromium-51 release essay – up to 70% cancer cell death with 25:1 TIL-to-tumor cell ratio.

Conclusion: The methods for the robust and fast TIL-generation from pancreatic cancer tissue were optimized using a cytokine cocktail of IL-2/IL-15/IL-21 even for small biopsies. TILs show a central-memory and effector memory phenotype and are monoclonal, which is a good prerequisite for efficient T-cell therapy.

Disclosure of Interest: None declared

P0712 GASTROKINE AS A NOVEL POTENTIAL BIOMARKER FOR PREMALIGNANT PANCREATIC LESIONS

G. M. Seleznik¹, T. Reding¹, A. Zabel¹, E. Diamantis², E. Angst², A. Perren², M. Heikenwalder³, R. Graf¹

¹Swiss HPB Center, Visceral & Transplantation Surgery, University Hospital Zurich, Zurich, ²Institute of Pathology, University of Bern, Bern, Switzerland, ³Institute for Virology, Helmholtz-Centre Munich, Munich, Germany

Contact E-mail Address: gittamaria.seleznik@usz.ch

Introduction: Pancreatic cancer is a uniformly lethal disease that is difficult to diagnose at an early stage and even more difficult to cure. The current methods for diagnosing pancreatic cancer are ineffective and/or impractical for identifying smaller, potentially curable lesions. Gastrokine (GKN1-3) is a secreted auto-/paracrine protein in the gastric mucosa which shows growth factor or ‘cytokine-like’ activity toward gastric epithelial cells. GKN expression has so far been shown predominantly in the stomach, except for trace levels in the uterus and placenta and in the duodenum. In the stomach, GKN expression is confined to the gastric epithelium, where individual paralogs (GKN1-3) manifest remarkable cell-type-specific localization on different mucus-secreting epithelial lineages. Definitive physiological functions have not been formally ascribed to GKNs. The limited published evidence suggests fundamental roles in regulating gastric epithelial homeostasis and tumor suppression. While current research focuses on the exploration of tumor-suppressive properties of GKN1 regarding gastric tumors, nothing is known about GKN expression and function in other organ systems. Within the frame of a whole genome microarray analysis of a mouse model for pancreatic carcinogenesis (KrasxPtf1a), we have found gastrokines strikingly upregulated in the pancreas during pre-neoplastic conversion.

Aims & Methods: The aim of the study is to investigate gastrokine expression and function during pancreatic carcinogenesis. Gastrokine mRNA expression was confirmed by RT-PCR in human patients and different mouse models (pancreatitis and pancreatic carcinogenesis). Data mining of human microarray results focused on benign and malignant pancreatic diseases. Gastrokines were visualized by immunohistochemistry. The presence of GKNs in different stages of pre-malignant lesions was defined by IHC and mucin co-expression analysis. Secretion of GKNs in mouse pancreatic juice was shown by proteomic analysis. In vitro acinar assays were performed to analyze GKN expression during acinar transdifferentiation.

Results: Gastrokine expression is highly upregulated during the early stages of mouse pancreatic carcinogenesis. GKN transcripts are also increased in human patients in peri-tumoral tissue and in benign pancreatic tumors. GKN expression is neither detected in healthy pancreas nor in samples with pancreatic inflammation. Immunohistochemistry reveals strong GKN expression in premalignant PanIN lesions. GKN1 is abundant in the cytoplasm of dysplastic epithelium whereas GKN2 is localized to associated inflammatory cells. GKNs are absent from mouse and human PDAC. GKNs are co-expressed with Muc5ac and Muc2 in human patients indicating an expression on intestinal type IPMNs. ELISA and proteomic analysis in mice confirmed the secretion of GKN1 into pancreatic juice but not serum.

Conclusion: We identified for the first time gastrokine expression in neoplastic human and mouse pancreatic tissues. GKN expression is specific for premalignant PanIN lesions and it is secreted into the pancreatic juice during pancreatic carcinogenesis. Therefore, gastrokine could serve as a potential biomarker for early pancreatic pre-neoplastic lesions and benign tumors. Furthermore, determination of GKNs in pancreatic juice may provide a tool to identify patients at risk.

Disclosure of Interest: None declared

P0713  THE EFFICACY AND PITFALLS OF ENDOSCOPIC ULTRASOUND IN THE DIFFERENTIAL DIAGNOSIS OF PANCREATIC CYSTS

Y. Kayar¹, M. Tozlu¹, H. Senturk¹, A. T. Ince¹, A. Danalioglu¹, D. S. Arici²

¹Department of Internal Medicine, Division of Gastroenterology, ²Department of Pathology, Bezmialem Vakif University, Istanbul, Turkey

Contact E-mail Address: ykayar@yahoo.com

Introduction: Pancreatic cystic lesions (PCL) are increasingly being diagnosed in clinical practice. However the efficacy of several methods in differential diagnosis is still uncertain and differs between centers. We investigated the role and contribution of endosonography (EUS) and EUS-guided fine needle aspiration (EUS-FNA) in the differential diagnosis of PCL.

Aims & Methods: We identified all patients who underwent EUS and EUS-FNA for PCL in our center from 2011 to 2014. Data were collected on demographics, clinical, laboratory and imaging, the results of biochemical and cytological evaluation of cyst fluid, in case it is available.

Results: There were 379 patients (45% male, mean age 57,6 ± 14,6 years, range 17-90). PCL were more commonly diagnosed between the ages of 60-69: 28% and 50-59: 23%. Three in four of the patients were symptomatic (excluding pseudocysts, 42%) and diabetes mellitus was present in 1/3. The mean cyst size was 38.2 ± 31,1 mm (median: 30 mm, range; 4-220 mm). A total of 268 FNAs were attempted, 3 of which were unsuccessful. In cytology, 15(10%) showed insufficient, and 41 (27%) non-specific findings. Out of 154 cytological examination, a specific diagnosis was reached in 98 (63%). Overall, out of 379 cases, a specific diagnosis could be reached in 274 (73%) patients: 95 (25%) were pseudocysts, 78 (21%) mucinous cysts, 40 (11%) cystic tumors, 38 (10%) serous cystadenomas (SCA), and 23(6%) other cystic lesions. In 51 cases surgery was performed. Diagnosis included, mucinous cystic tumor (MCN) (6), intraductal papillary mucinous neoplasm (10), cystic neuroendocrine tumor (2), SCA (3), solid pseudopapillary tumor (4), pseudocyst (4), cystic tumor (12), solid tumours with cystic degeneration, and cysts of different origin (10). The kappa value for the diagnosis of mucinous cyst between imaging-surgery were 0.688 and EUS-surgery, 0.658, respectively.The kappa level between EUS vs. imaging in making a diagnosis of pseudocyst was %77,7 (p: 0.001). In all serous cysts, the cyst amylase level was below 2000 U/L and CEA was below 5 ng/ml but the levels of amylase and CEA showed a wide variation in all other types of cysts. In 9% of pseudocyst, the amylase were below 2000 U/L. In two surgically diagnosed MCN, the cyst CEA were below 5 ng/ml, and in one of them amylase was over 20.000 U/L. In another MCN, CEA was 40 ng/ml and amylase was over 20.000 U/L. While in all serous cysts the serum CA19-9 was below 37 U/L. In 80 % of cystic malignancies it was over 37 U/ml.

Conclusion: The diagnostic value of imaging and EUS towards PCL seems to be similar. EUS-FNA obtained cyst cytology reached a specific diagnosis in 63% of the cases. While cyst CEA and amylase levels showed a variable diagnostic capacity and were sometimes, misleading, serum CA 19-9 level seemed to be discriminatory between benign and, already, malignant lesions.

Disclosure of Interest: None declared

P0714 NEUROGENESIS AND ANGIOGENESIS IN PANCREATIC CANCER BEHAVE CONCORDANTLY AND EXHIBIT DISTINCT TRANSCRIPTIONAL PROFILES

I. Kröger¹, I. E. Demir¹, S. Teller¹, H. Friess¹, G. O. Ceyhan¹

¹Department of Surgery, Klinikum rechts der Isar, TU München, München, Germany

Contact E-mail Address: isabel.kroeger@hotmail.com

Introduction: Pancreatic cancer (PCa) is characterized by increased intratumoral nerve density and nerve hypertrophy. Conversely, the density of vessels and tumor perfusion in PCa were reported to be decreased when compared to normal pancreas, creating a hypoxic tumor microenvironment. This observation raises the question whether neurogenesis and angiogenesis in PCa behave oppositely or even suppress each other.

Aims & Methods: The current study aimed to elucidate the interaction between neurogenesis and angiogenesis and to decipher the molecular actors that drive generation of nerves and vessels in PCa. Human PCa specimens (UICC stages II-III, n= 57) were analyzed for the density of all (CD31⁺) vessels and all (S100⁺) nerves in the whole tumor area via a novel triple immunofluorescence/ immunohistochemistry analysis that additionally co-labeled cancer cells via cytokeratin-19 (CK19). The density of nerves and vessels were correlated to each other and to the severity of neural invasion (NI) and angioinvasion. The transcriptomic profile within tumor tissue of patients with strong neurogenesis or strong angiogenesis was compared to that of patients with little neuro- or angiogenesis via profiler PCR arrays.

Results: 41 out of 57 patients exhibited NI, whereas angioinvasion was detected in only one out of 57 patients. The mean vessel size and mean nerve size correlated positively (Sperman’s coefficient r=0.43, p=0.0013), and the total area of nerves increased in parallel with the total area of vessels in the analyzed specimens (r=0.28, p=0.04). The frequency of NI increased in concordance with the amount of tumor innervation (r=0.25, p=0.059). There was no association between vessel density and NI. Patients with more pronounced tumor angiogenesis had greater intratumoral amounts of matrix metalloproteinase (MMP9), beta-III-integrin, TgfbetaR1, CXCL9, and lower levels interferon-alpha-1 (Ifna1) and LECT1. Furthermore, patients with more neurogenesis exhibited intratumoral upregulation of interleukin-6, TrkA, Nr1I2, NGF, CXC3CR1, and Neurotrophin-3, and downregulation of ciliary neurotrophic factor (CNTF).

Conclusion: Angiogenesis and neurogenesis behave concordantly in PCa. Interleukin-6 and neurotrophic factors may be responsible for the remarkably high prevalence of NI in PCa.

Disclosure of Interest: None declared

P0715 TM4SF1 PROMOTES INVASION AND METASTASIS OF PANCREATIC CANCER VIA REGULATING THE EXPRESSION OF DDR1

J. Yang¹, J. Cao¹, Z. Li², L. Xu¹

¹Digestive Endoscopic Diagnosis and Treatment Center, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, ²Dept of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China

Contact E-mail Address: emmafcwf@126.com

Introduction: Pancreatic ductal adenocarcinoma (PDAC) has increasingly mortality rates because it has highly invasion and metastasizes rapidly. We previously found that Transmembrane-4-L-six-family-1(TM4SF1), a four-transmembrane L6 family member, was highly expressed in human pancreatic cancer tissues and PDAC cell lines. Also, TM4SF1 promoted cancer cells invasion and metastasis in vitro and in vivo. Here, we investigated the mechanism of TM4SF1-mediated invasion and metastasis in PDAC.

Aims & Methods: We used small interfering RNAs in PANC-1, AsPC-1 to study the function of TM4SF1 on regulating invadopodia, which mediated the extracellular matrix (ECM) degradation to support cancer cells invasion. We investigated the ability of TM4SF1 to regulate the expression of discoidin domain receptor 1 (DDR1) using real-time PCR, immunoblot, immunofluorescence and coimmunoprecipitation analyses. And the effects on cell migration and invasion were analyzed by Transwell chambers and Matrigel invasion chambers. Finally, the clinical relevance of TM4SF1 and DDR1 was investigated using adjacent normal pancreatic tissues and pancreatic cancer specimens.

Results: In human PDAC cell lines, TM4SF1 facilitated the activation of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) by western blot and gelatin zymography analysis. We found that the number of invadopodia reduced by 73% and the area of the ECM degradation decreased by 63% in PANC-1 when TM4SF1 was silenced compared to the control cells. Silencing of TM4SF1 reduced the percentage of cells with invadopodia by approximately 70% and decreased the ECM degradation by 46% in AsPC-1. Also, TM4SF1 silencing down-regulated the expression of DDR1 and inhibited cancer cells migration and invasion. TM4SF1 expression colocalized with DDR1 in PANC-1 and AsPC-1 cells by immunofluorescence analysis. Coimmunoprecipitation assays showed an interaction between TM4SF1 and DDR1. Overexpressed DDR1 rescued the inhibitory effect of TM4SF1 silencing on PDAC cell lines migration and invasion, suggesting that DDR1 was involved in TM4SF1-mediated migration and invasion. When DDR1 was overexpressed in PANC-1 and AsPC-1, MMP2 and MMP9 protein expression levels increased. Moreover, TM4SF1 and DDR1 mRNA expression levels were both found to be almost 2 fold high in PDAC compared with adjacent normal pancreatic tissues. The scatter plots showed that TM4SF1 and DDR1 mRNA expression levels were positively correlated in PDAC tissues.

Conclusion: Taken together, our data suggest that a novel regulatory pathway involving TM4SF1, DDR1, MMP2 and MMP9, which mediates the ECM degradation and promotes invasion and metastasis in PDAC. Thus, TM4SF1 may be a potential therapeutic target.

Disclosure of Interest: None declared

P0716 NOVEL BIOMARKER PANEL FOR THE EARLY DETECTION OF PANCREATIC CANCER IN THE BLOOD

J. Namkung¹, Y. Choi¹, W. J. Lee², J. S. Heo³, J. K. Park⁴, D.-Y. Oh⁴, S. C. Kim⁵, C. M. Kang⁶, T. Park⁷, Y. Kim⁴, J.-Y. Jang⁴

¹IVD Business Unit, SK Telecom, Seoul, ²National Cancer Center, Koyang, ³Samsung Medical Center, ⁴Seoul National University College of Medicine, ⁵Asan Medical Center, ⁶Severance Hospital, ⁷Seoul National University, Seoul, Republic of Korea

Contact E-mail Address: Novel biomarker panel for the early detection of pancreatic cancer in the blood.

Introduction: Current pancreatic cancer marker, CA19-9 has limited diagnostic accuracy. In this study, we aimed to identify a multi-marker panel capable of detecting early stage pancreatic cancer eligible for surgical treatment, with high sensitivity and specificity. We conducted a thorough candidate marker screening and then validated the final panel in a large multicenter clinical study.

Aims & Methods: Pancreatic cancer biomarker candidates from data mining of commercial and public databases were listed. Additional candidates were recruited by identifying differentially expressed genes from our tissue microarray experiments. Initially 1000 candidates with supporting evidence from more than two sources were selected and their serum protein levels were measured using Multiple Reaction Monitoring Mass Spectrometry (MRM-MS) in 50 resectable pancreatic ductal adenocarcinoma (PDAC) samples and 50 healthy or benign samples. Of the candidates, 54 proteins with high ranked diagnostic performance were selected for further investigation. Using MRM-MS, the candidate markers were evaluated in blood samples from five major clinical centers in Korea. The study subjects included 401 cases of PDAC patients (232 in stage I-II), and 458 controls (300 normal individuals and 158 benign diseases including pancreatitis and non-malignant pancreas cystic tumors). All the possible biomarker combinations consisted of up to 5 proteins among 54 candidates were investigated using Support Vector Machine. Then, 7 multiple marker combinations were selected by 10 fold cross-validation to have sensitivity greater than 0.85 at a fixed specificity of 0.9. The final panel was selected by considering biological relevance with cancer development, dynamic ranges in the blood and reliability of the measurements. The panel was validated using ELISA and an automated immunoassay system in the 859 multicenter case-control samples and additional 149 other cancer samples.

Results: A panel comprising CA19-9, LRG1 and TTR was determined to be the best biomarker. This triple marker panel significantly improved diagnostic performance of CA19-9 and we obtained consistent results from the immunoassay analyses. The area under the ROC curve (AUC) of the panel was 0.941 and the sensitivity was 0.850 whereas those of CA19-9 alone were 0.847 and 0.746, respectively. Even in cancer samples of stage I-II, the performance was significantly improved to AUC 0.921 and sensitivity 0.820 whereas CA19-9 had 0.82 and 0.677 respectively. The increase in AUC was greater than 10% (Delong’s test p-value < 0.001). Additionally, the panel was highly selective for PDAC and had AUC of 9% greater than CA19-9 in the analysis of PDAC vs. other cancers.

Conclusion: A new diagnostic panel showed advantages over CA19-9 in terms of sensitivity and specificity as a pancreatic cancer specific tumor marker. Noticeably, this panel consistently performed well for detection of relatively early stage pancreatic cancer samples, which suggests potential of the panel as a screening test for early detection of PDAC.

Disclosure of Interest: None declared

P0717 THE ANTI-DIABETIC DRUG METFORMIN INHIBITS PANCREATIC CANCER CELL PROLIFERATION IN VITRO AND IN VIVO: STUDY OF MICRORNAS ASSOCIATED WITH THE ANTI-TUMOR EFFECT OF METFORMIN

K. Kato¹, H. Kamada¹, K. Kobayashi¹, T. Fujimori¹, T. Masaki¹

¹Gastroenterology and Neurology, Kagawa University, Kagawa, Japan

Introduction: Recent studies suggest that metformin, which is a commonly used oral anti-hyperglycemic agent of the biguanide family, may reduce cancer risk and improve prognosis, but the detailed mechanisms by which metformin affects various cancers, including pancreatic cancer, remain unknown.

Aims & Methods: The goal of the present study was to evaluate the effects of metformin on human pancreatic cancer cell proliferation in vitro and in vivo, and to study microRNAs (miRNAs) associated with metformin’s anti-tumor effect. We used the human pancreatic cancer cell lines Panc1, PK1 and PK9 to study the effects of metformin on human pancreatic cancer cells. Athymic nude mice bearing xenograft tumors were treated with or without metformin. Tumor growth was recorded after 5 weeks, and the expression of cell cycle-related proteins was determined. In addition, we used miRNA array tips to explore the differences among miRNAs in Panc1 cells bearing xenograft tumors treated with or without metformin in vitro and in vivo.

Results: Metformin inhibited the proliferation of Panc1, PK1 and PK9 in vitro. Metformin blocked the cell cycle in G0/G1 in vitro and in vivo. This blockade was accompanied by a strong decrease of G1 cyclins, especially in cyclin D1, cyclin-dependent kinase 4 (Cdk4), and Cdk6, and by a decrease in retinoblastoma protein (Rb) phosphorylation. In addition, metformin reduced the phosphorylation of EGFR and IGF-1R in vitro and in vivo. Moreover, metformin reduced the phosphorylation of EGFR at Tyr845. The miRNA expression was markedly altered by the treatment with metformin in vitro and in vivo. Various miRNAs altered by metformin may also contribute to tumor growth in vitro and in vivo.

Conclusion: Our results revealed that metformin inhibits human pancreatic cancer cell proliferation and tumor growth, possibly by suppressing the cell-cycle-related molecules via alteration of miRNAs.

Disclosure of Interest: None declared

P0718 EPITHELIAL-TO-MESENCHYMAL TRANSITION (EMT) IN HUMAN PANCREATIC CANCER: ASSOCIATION WITH DISEASE DISSEMINATION AND RECURRENCE

M. Tacelli¹, A. Gallioli¹², S. Magrì¹, F. Gavazzi², A. Zerbi², P. Spaggiari³, M. Roncalli³, P. Bianchi¹⁴, G. Basso¹, G. Celesti¹, M. Montorsi²⁵, A. Malesci⁶, L. Laghi¹

¹Laboratory of Molecular Gastroenterology, ²Departments of General Surgery, ³Pathology, ⁴Analytical Laboratory, ⁵Hunimed University Chancellor, Humanitas Research and Clinical Hospital, Rozzano, ⁶Dept. of Translational Medicine, University of Milan, Milan, Italy

Contact E-mail Address: matteo.tacelli@gmail.com

Introduction: EMT is an emerging mechanism underlying cancer cell dissemination. EMT is driven by transcription factors (TFs; TWIST1, ZEB2, SLUG) coupling the expression of M genes (VIMENTIN, CDH2) with the repression of E ones (CDH1), thus conferring to cancer cells fibroblast-like morphology and enhanced migratory properties. Although EMT occurs early in mouse model of pancreatic cancer (PC), evidence in human PC remain scattered.

Aims & Methods: Human PC cell-lines (HPAF-II, HPAC, PANC-1, MIAPaCa-2) were characterized as to the expression of CDH1-2 and EMT-TFs mRNA. In tissue specimens from PC patients, the presence of stromal cells expressing TWIST1 was assessed by immunohistochemistry at the tumor center (^CT; n=99) and at the posterior resection margin (^PRM; n=79). Association between TWIST1+ cells, clinical-pathological features, and disease-free survival (DFS) were assessed by logistic regression, Cox model (N-adjusted, stage IV and DFS < 90 days excluded), and Kaplan-Meier curves. The levels of EMT-TFs mRNA in the bloodstream of PC patients were measured by qRT-PCR (n=45; heathy controls, n=30), and circulating tumor cells (CTCs) were searched by combining in-situ hybridization (chromosome 7 and 20) with VIMENTIN/CDH1 immune-reactivity (n=10).

Results: CDH1+ PC cells (HPAF-II, HPAC) did not show EMT-TFs, while CDH1-negative cells (PANC-1, MIAPaCa-2) expressed TWIST1 and SLUG. Most (71/99; 72%) specimens harbored TWIST1^CT+ cells; the only pathological feature associated with TWIST1^CT+ cells was neural invasion [71/71 TWIST1^CT+ cases vs 23/28 (82%) negative ones; p=0.001]. In pathological specimens, the presence of TWIST1^PRM+ (51/79; 64.5%), was significantly lower than that of TWIST1^CT+cells (42/51, 82%, showing TWIST1^CT+/PRM+, but 14/28, 50%, TWIST1 ^PRM-negative harboring TWIST1^CT+; p=0.003). TWIST1^CT+ cells had no prognostic value [(HR&95%CI) 1.27, 0.65-2.48; p=.47], while TWIST1^PRM+ cells increased the risk of recurrence (3.12, 1.35-7.26; p<.008), either local (3.35, 1.25-9.0; p=.017), either metastatic (5.8, 1.32-25.6; p=.02), and were associated with a worse DFS (log-rank test, p=0.002). In patient bloodstream, we detected increased mRNA levels of CDH1 (2^-ΔCTmedian, 2.03E-07 vs 8.37E-08, in controls; p=0.03), but also of TWIST1 (3.95E-08 vs 2.06E-08; p=0.06), ZEB2 (1.52E-05 vs 3.63E-06; p=0.006), and SLUG (2.36E-08 vs 9.09E-13; p < 0.001). Eventually, aneuploid CTCs expressing VIMENTIN (1.7 cells/ml) or CDH1 (2.1/ml) were detected.

Conclusion: A set of established PC cells, shows no E but M hallmarks and expresses EMT-TFs. The association between TWIST1^PRM+ cells and disease recurrence suggests the involvement of EMT in PC progression. EMT-TF mRNA levels and aneuploid M-CTCs in the bloodstream indicate ongoing EMT in a subset of PC cells into the circulation. PC comprises cell populations with M features, ignored so far but likely relevant for local and distant dissemination.

Disclosure of Interest: None declared

P0719 IMPACT OF PHARMACOLOGICAL MACROPHAGE DEPLETION ON THE PROGRESSION OF PANCREATIC NEUROENDOCRINE NEOPLASMS

S. Krug¹, R. Abbassi², H. Griesmann¹, M. Egidi¹, A. Rinke², T. Gress², P. Michl¹

¹Department of Gastroenterology and Hepatology, University Hospital Halle (Saale), Halle, ²Department of Gastroenterology and Endocrinology, University Hospital Marburg, Marburg, Germany

Contact E-mail Address: Krugsebastian@t-online.de

Introduction: Pancreatic neuroendocrine tumors (PNETs) are a heterogeneous group of neuroendocrine neoplasms with distinct biological behaviour and response to treatment. Efforts have been taken to improve the survival for patients at advanced stage, however, conventional chemotherapy is still recommended as standard treatment with limited efficacy. Previous reports indicate that the infiltration of tumor-associated macrophages (TAMs) in PNETs strongly correlates with proliferation and metastases.

Aims & Methods: Evaluation of the impact of the liposomal clodronate as pharmacological tool for macrophage depletion in-vitro and in-vivo.

The effect of liposomal clodronate on cell-viability was analysed in J774 and RAW myeloid cells and isolated murine bone macrophages as well as CD11b+ cells of RIP1-Tag2 pancreata which were evaluated by FACS. RIP1-Tag2 mice were treated with either clodronate or liposomes alone to evaluate tumor progression, proliferation, angiogenesis and macrophage infiltration by FACS and immunohistochemistry.

Results: Liposomal clodronate inhibited the proliferation of monocytic J774 and RAW cells and murine bone macrophages. In contrast, cell-viability of neuroendocrine BON-1 and QGP-1 cells was not affected by this treatment. FACS analyses of RIP1-Tag2 mice treated with clodronate confirmed the selective depletion of macrophages. In RIP1-Tag2 mice liposomal clodronate reduced the evolution of invasive beta-cell tumors. Furthermore, proliferation of tumor cells and angiogenesis within the tumors were markedly reduced.

Conclusion: Liposomal clodronate selectively depletes macrophages and disrupts tumor progression in the RIP1-Tag2 neuroendocrine tumor model associated with reduced angiogenesis.

Disclosure of Interest: None declared

P0720 THE HIGH FREQUENCY OF PD-1 IN PERIPHERAL CD4+ T CELLS OF PANCREATIC DUCTAL ADENOCARCINOMA IS POTENTIALLY USEFUL FOR DEVELOPMENT OF THE NOVEL DIAGNOSTIC METHOD AND PREDICTION OF CHEMOTHERAPY RESPONSIVENESS

T. Komura¹, Y. Sakai²³, T. Wada³, S. Kaneko¹²

¹Disease Control and Homeostasis, ²Department of Gastroenterology, ³ Department of Laboratory Medicine, Kanazawa University, Kanazawa, Japan

Contact E-mail Address: t.komura0507@gmail.com

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is the lethal malignancy with extremely poor prognosis due to difficulty of diagnosis in early stage as well as the high grade of malignant potential. Therefore, detailed biological features including the immune-pathology are to be examined for development of the novel diagnostic method and therapeutic approach including immunotherapy.

Aims & Methods: We here examined the peripheral blood of PDAC patients in the context of programmed cell death-1 (PD-1) molecule, which is expressed on activated lymphocytes and regulate host immune response, and their clinical features. Fifty PDAC patients (Age; 68.0 ± 10.1, Gender; Male/Female=29/21, Stage I/II/III/IV=7/12/13/18) and twenty seven healthy volunteers (Age; 64.1 ± 8.7, Gender; Male/Female=13/14) were enrolled with the informed consent of the study. Peripheral blood mononuclear cells (PBMCs) were isolated from heparinized venous blood using Ficoll-Hypaque density gradient centrifugation. Obtained PBMCs were incubated with fluorescent antibodies, PD-1, CD4, CD8, CD25, CD127, and these expression levels were analysed using flow cytometry. Furthermore, we extracted RNA from CD4+ T cells using anti-CD4 magnet beads from PBMCs, and examined the expression level of PD-1 and FoxP3, which is transcriptional factor for regulatory T cells, on these cells.

Results: Flow cytometry analysis showed that the frequency of CD4 + PD-1+ cells, not CD8 + PD-1+ cells, was significantly increased in the PBMCs of PDAC patients (6.4 ± 2.9%), compared to healthy volunteers (3.8 ± 2.1%, p=0.001). Then, PD-1 mRNA expression level was also increased in CD4+ cells of PDAC patients. On the other hand, CD4 + CD25 + CD127low/- cells, which is representative regulatory T cells, was increased in the PBMCs of PDAC patients (3.8 ± 1.4%), compared to healthy volunteers (2.9 ± 1.4%, p=0.022), while FoxP3 mRNA expression level was not increased in CD4+ cells of PDAC patients.

We observed that the frequency of CD4 + PD-1+ T cells and regulatory T cells was no correlation with clinical stages as well as serum CEA and CA19-9 values in PDAC patients. We examined whether the frequency of these populations were correlated with clinical outcome of PDAC patients or not, among the enrolled 35 PDAC patients who underwent chemotherapy. The frequency of CD4 + PD1+ T cells was significantly increased in patients with poor response to chemotherapy (p=0.002), although the frequency of regulatory T cells was not. There was no significant difference in overall survival among the frequency of CD4 + PD1+ T cells as well as regulatory T cells populations.

Conclusion: The frequency of CD4 + PD-1+ T cells was increased even in early stage of PDAC patients, implying assessment of the frequency of CD4 + PD-1+ T cells in PBMCs is the possible novel diagnostic approach in early stage. In addition, the high frequency of CD4 + PD-1+ T cells population of PDAC patients was predictive of poor response of chemotherapy.

Disclosure of Interest: None declared

P0721 FACTORS ASSOCIATED WITH CANCER WORRIES IN INDIVIDUALS PARTICIPATING IN ANNUAL PANCREATIC CANCER SURVEILLANCE

I. C. Konings¹, G. N. Sidharta², F. Harinck¹, M. A. Kuenen², C. M. Aalfs³, J.-W. Poley¹, E. M. Smets⁴, A. Wagner⁵, A. van Rens⁶, F. P. Vleggaar⁷, M. G. Ausems⁸, P. Fockens⁹, J. E. van Hooft⁹, M. J. Bruno¹, E. M. Bleiker²⁶, on behalf of the Dutch Research Group on Pancreatic Cancer Surveillance in High-Risk Individuals

¹Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, ²Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, ³Department of Clinical Genetics, ⁴Department of Medical Psychology, Academic Medical Center, Amsterdam, ⁵Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, ⁶Family Cancer Clinic, The Netherlands Cancer Institute, Amsterdam, ⁷Department of Gastroenterology and Hepatology, ⁸Department of Clinical Genetics, University Medical Center, Utrecht, ⁹Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands

Contact E-mail Address: i.konings@erasmusmc.nl

Introduction: There is growing interest in surveillance for pancreatic cancer (PC) in high-risk individuals to detect early stage PC or precursor lesions. When assessing the feasibility of such surveillance, it is important to also address participants’ psychological burden. Previously, we reported that repeated participation in annual surveillance imposes low psychological burden. However, a subgroup of individuals showed intermediate to high levels of cancer worry. The aim of this study was to evaluate possible factors associated with these cancer worries.

Aims & Methods: High-risk individuals (estimated lifetime risk of PC ≥ 10%), participating in an annual prospective multicenter Dutch EUS-MRI based PC surveillance program, were invited to complete an annual questionnaire to assess their cancer worries with the Cancer Worry Scale (CWS). The questionnaire was sent after genetic counseling (T0), after intake for participation but prior to the first MRI and EUS (T1), and thereafter annually after MRI and EUS (T2-T7). Individuals who scored ≥ 12 points on the CWS on each available questionnaire were defined as having intermediate to high cancer worries.

Results: A total of 688 out of 763 questionnaires were returned (90%) by 166 out of 178 participants (93%): 41, 92, 149, 123, 106, 81, 64 and 32 questionnaires at each of the eight time points respectively. The mean age of participants was 52 years with a mean follow-up of 49 months. The mean CWS-score was 12.8 (range 8-26). A total of 66 individuals (40%) scored ≥ 12 points on the CWS at each available questionnaire. Both univariate and multivariate analysis showed three factors to be associated with intermediate to high cancer worries: proven carriers of a PC-associated gene mutation (as opposed to familial pancreatic cancer individuals in whom no known gene mutation could be detected) (P=0.04); scoring ≥ 20 points on the Hospital Anxiety and Depression Score (HADS) at least once (P=0.05); and having a family member affected with pancreatic cancer <50 years of age (P<0.01). Not associated were gender, education level, marital status, a personal history of cancer, the detection of a cystic lesion nor a shortened interval during surveillance.

Conclusion: A total of 40% of individuals participating in annual pancreatic cancer surveillance had intermediate to high cancer worries at all available psychological questionnaires. We identified three factors to be associated with these worries: carriership of a pancreatic cancer associated gene mutation, a high HADS score, and a family member affected with pancreatic cancer under 50 years of age. These associated factors can help to identify patients ‘at risk’ for experiencing cancer worries who might benefit from psychosocial support.

Disclosure of Interest: None declared

P0722 PREVALENCE AND PROGRESSION OF CYSTIC PANCREATIC PRECURSOR LESIONS DIFFER BETWEEN TWO GROUPS AT HIGH RISK OF DEVELOPING PANCREATIC CANCER

I. C. Konings¹, F. Harinck¹, J.-W. Poley¹, C. M. Aalfs², A. van Rens³, N. C. Krak⁴, A. Wagner⁵, C. Y. Nio⁶, R. Sijmons⁷, H. van Dullemen⁸, F. P. Vleggaar⁹, M. G. Ausems¹⁰, P. Fockens¹¹, J. E. van Hooft¹¹, M. J. Bruno¹, on behalf of behalf of the Dutch Research Group on Pancreatic Cancer Surveillance in High-Risk Individuals

¹Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, ²Department of Clinical Genetics, Academic Medical Center, ³Family Cancer Clinic, The Netherlands Cancer Institute, Amsterdam, ⁴Department of Radiology, ⁵Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, ⁶Department of Radiology, Academic Medical Center, Amsterdam, ⁷Department of Clinical Genetics, ⁸Department of Gastroenterology and Hepatology, University Medical Center, Groningen, ⁹Department of Gastroenterology and Hepatology, ¹⁰Department of Clinical Genetics, University Medical Center, Utrecht, ¹¹Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands

Contact E-mail Address: i.konings@erasmusmc.nl

Introduction: Individuals at high risk of developing pancreatic ductal adenocarcinoma (PDAC) are (1) carriers of a mutation that predisposes to PDAC, and (2) individuals who have no known gene mutation but who have a strong family history of PDAC (familial pancreatic cancer, FPC). The genes involved in the development of FPC are unknown. Consequently, given the presumed autosomal dominant inheritance pattern of FPC, by definition half of these FPC-individuals are not at increased risk. It is still unclear whether the prevalence and natural progression of cystic precursor lesions are equal in both risk groups. The aim of our study was therefore to compare prevalence and progression of lesions between the two groups.

Aims & Methods: Individuals with an estimated lifetime risk of developing PC ≥10% underwent annual pancreatic surveillance with magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) in an ongoing prospective multicenter study. Individuals included are (1) first degree relatives (FDR) of FPC cases, defined as families with PDAC in ≥2 FDR, in ≥3 relatives, or in ≥2 relatives with ≥ 1 case aged <50 at diagnosis, and (2) mutation carriers of PC-prone gene mutations (all CDKN2A mutation carriers and Peutz-Jeghers patients; BRCA1 or 2 mutation carriers, p53 mutation carriers and Lynch syndrome patients with ≥2 family members affected with PDAC). Progression of a lesion was defined as growth ≥4 mm or the development of malignant features.

Results: We included 172 individuals, of whom 90 (52%) were mutation carriers and 82 (48%) were FPC individuals. There was no significant difference in follow-up between groups (mean 41 months vs 44 months respectively, P=0.35). A total of 36 cysts were detected in 90 mutation carriers (40%) and 47 cysts in 82 FPC-individuals (57%, P=0.12). Significantly more cysts ≥10 mm were detected in FPC individuals than in mutation carriers (15% vs 4%, P=0.05). However, the cystic lesions detected in mutation carriers were significantly more likely to progress than those in FPC individuals (19% vs 2%, P=0.04). The number of lesions per individual, the presence and number of chronic pancreatitis features, and the age of individuals at diagnosis of a cystic lesion did not differ between both groups.

Conclusion: FPC individuals had a higher prevalence of cystic lesions ≥10 mm, which is remarkable given the fact that half of these FPC individuals are probably not at increased risk to develop pancreatic neoplasia (presumed autosomal dominant inheritance of unknown mutation). However, the lesions in mutation carriers were more likely to progress during follow-up. These results could lead to better tailored surveillance strategies, to identify high-grade dysplastic lesions or PDAC more adequately.

Disclosure of Interest: None declared

P0723 HOW TO DEAL WITH INCIDENTAL PANCREATIC CYSTIC NEOPLASM; DETECTION OF MALIGNANCY

J. S. Kim¹, H. J. Kim¹, B. J. Lee¹, J. H. Kim¹, J. E. Yeon¹, J.-J. Park¹, H. S. Lee², K. S. Byun¹, C. D. Kim², Y.-T. Bak¹

¹Internal Medicine, Korea University Guro Hospital, ²Internal Medicine, Korea University Anam Hospital, Seoul, Republic of Korea

Contact E-mail Address: kimjs@kumc.or.kr

Introduction: Careful selection for surgical intervention or radiologic and clinical surveillance is important in the management of patients with pancreatic cystic neoplasms (PCNs). Although some PCNs require surgical resection, they are slow growing and have a favorable prognosis in contrast to ductal adenocarcinoma.

Aims & Methods: We aimed to evaluate natural course of PCNs and the detection of malignant transformation during follow-up according to the risk factors. We retrospectively reviewed the records of 301 patients with PCN incidentally diagnosed by using abdominal US, CT, or MRI. Cyst size was recorded as the maximum dimension measured on cross-sectional imaging. Presence of cyst features that are known potential risk factors for malignancy, such as thickened enhanced cyst walls, main pancreatic duct size >5 mm, non-enhanced mural nodules, abrupt changes in the main pancreatic duct caliber with distal pancreatic atrophy, and enhanced solid component, were also recorded. Patients were followed-up after an initial 3-month interval and then followed-up at 6 months and 12 months, followed by an annual follow-up. Malignant transformation of PCN during follow-up was defined as either histologic confirmation after surgical resection or evidence of metastatic or invasive disease from a suspected primary PCN on radiologic imaging.

Results: Of 301 patients, 19 were excluded (15 less than 1 year of follow-up, 4 underwent surgery for malignancy at initial diagnosis). Data from 282 patients were analyzed (mean age: 59.4 years, median follow-up: 28.5 months); 97 patients had risk factors such as cyst >3 cm or the presence of mural nodule. During surveillance, 41 patients showed changes in cysts (median duration: 24 months); 32 showed an increase in cyst size, and 9 showed a change in cyst characteristics. Cyst-related malignancy occurred in 5 patients (2.5%, 5/203), all who had risk factors and whose cysts showed changes. Post-operative morbidity was observed in 30 of 93 patients (32.3%); 2 died (1, intra-abdominal infection; 1, mechanical obstruction). Mortality was observed in 9 patients, with disease-specific death in only one.

Conclusion: Although the risk of malignant transformation was higher in patients with incidental PCNs than in the general population, the detection of malignancy or disease-specific mortality during surveillance was low, even in the high-risk group. Continued surveillance is important whether there are significant changes in PCNs.

Disclosure of Interest: None declared

P0724 EFFICACY OF PROPHYLACTIC GASTROJEJUNAL BYPASS IN PREVENTING GASTRIC OUTLET OBSTRUCTION SYMPTOMS IN UNRESECTABLE PERIAMPULLARY CANCER

J. Eden¹, S. Sanjeevi¹, A. Noorani¹, E. Rangelova¹, J. Blomberg¹, J. Tsai¹, M. Del Chiaro¹, L. Lundell¹, C. Ansorge¹

¹Department of Surgical Gastroenterology, Karolinska University Hospital, Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden

Contact E-mail Address: christoph.ansorge@ki.se

Introduction: Up to 33% of patients with preoperatively considered resectable periampullary cancer are deemed unresectable at laparotomy due to unexpected locally advanced or metastasized disease. The conversion from curative to palliative intent usually leads to the construction of a concomitant prophylactic gastrojejunal bypass (PGJB) as part of a double bypass to prevent eventual duodenal / gastric outlet obstruction (GOO) symptoms that may occur with further tumour progression. How PGJB subsequently affects the adequacy of oral intake in a palliative setting has not been fully clarified.

Aims & Methods: To investigate the effect of PGJB on GOO symptoms using established scoring systems. Observational study on patients with periampullary adenocarcinoma found to be unresectable at exploratory laparotomy between 2004 and 2014. The patients were grouped according to the palliative surgical management they had received into PGJB or exploration (EXP) alone. Data on oral intake before operation, at discharge and at follow up was retrieved from the patient’s medical records and classified according to the GOO scoring system. Postoperative complications were classified according to Dindo-Clavien and delayed gastric emptying (DGE) according to the ISGPS consensus definition.

Results: A hundred-eight patients were included, 94 underwent PGJB (14 EXP). The groups were comparable regarding demographical data and and, except for severe complications (17% PGJB vs 7% EXP), had similar postoperative outcomes and long-term survival. Clinically significant DGE occurred in 18 % of the PGJB group and in 7.7 % of the EXP group. Length of hospital stay was longer in the PGJB group (9 vs 6 days). Improved rates of oral intake could not be demonstrated for PGJB when compared to EXP. Regarding therapeutic efficacy, 40 % of patients with preoperative GOO symptoms had improved oral intake at discharge after PGJB and 46 % had full oral intake on follow up. 43 % had a sustainably improved oral intake (at discharge and follow up). Regarding prevention of GOO symptoms, 32 % of the non-symptomatic patients developed a temporarily decreased and 7% a prolonged decrease of oral intake. At a median follow-up time of 47 days, 73 % of patients had regained full oral intake; however, only 49 % had full oral intake at both discharge and follow-up after PGJB compared to 73 % with full oral intake at discharge and follow-up after EXP.

Conclusion: Prophylactic gastrojejunal bypass, usually part of a double bypass, is a major surgical procedure with high rates of associated morbidity and mortality. For this procedure, the present study failed to demonstrate acceptable results for the treatment and effective short-term / long-term prevention of gastric outlet obstruction symptoms. Since primary gastric outlet obstruction develops in only 10-20 % of all patients with periampullary cancer, less invasive on-demand strategies may be discussed as alternatives to prophylactic surgery.

Disclosure of Interest: None declared

P0725 VALIDATION OF THE FUKUOKA´S INTERNATIONAL CONSENSUS FOR INTRADUCTAL PAPILLARY MUCINOUS TUMOR OF THE PANCREAS

J. C. Ardengh¹², E. Taglieri², O. Micelli-Neto², E. T. ARDENGH², R. Kemp³, J. S. dos Santos¹

¹Surgery and Anatomy of HCFMRP-USP, HCFMRP-USP, ²Endoscopic Department, Hospital 9 de Julho, São Paulo, ³Surgery and Anatomy of HCFMRP-USP, HCFMRP-USP, Ribeirão Preto, Brazil

Contact E-mail Address: jcelso@uol.com.br

Introduction: The anatomic classification of intraductal papillary mucinous tumor (IPMT) is difficult to understand. Despite the involvement of the main pancreatic duct (MPD) having a greater chance of malignancy, the branch duct remains a major challenge in relation to diagnosis and the decision of the treatment to be performed. There are several factors to predict the presence of malignancy, but they are still intense debate about, and there are many questions regarding which is the best malignancy predictor?

Aims & Methods: The aim of this study was to evaluate the effectiveness and accuracy of the latest international consensus to predict malignancy of IPMT. Data from 203 patients with pancreatic mucinous neoplasm identified by imaging and referred to the endoscopy department were prospectively collected to undergo endosonography-guided fine needle aspiration (EUS-FNA), between January 2008 and April 2014. We evaluated and compared the malignancy predictors factors described by the Fukuoka´s International Consensus described in 2012.

Results: According to the EUS images, results of laboratory tests and microhistology obtained by EUS-FNA, it was observed that the larger cysts > 2.5 cm have a higher chance of malignancy (50% versus 19%; p <0.001), with sensitivity and a specificity of 70% and 69.2%, respectively. The solid component was present in 30% of malignant tumors compared to 11.9% of benign (p = 0.006). The presence of solid component cysts larger than 2.5 cm has preditive positive value (PPV) 68% (p = 0.001) while his absence of cysts of any size has a PPV of 88% (p = 0.006). The MPD was normal in patients with no invasion (86% vs 60%, p <0.0001). The BD-IPMT had more results benignity (88.1%) while the MD-IPMN had the highest frequency among malignant lesions (41.2%) [p <0001]. The presence of one major criteria is associated with the presence of tumor by 55% (p < 0.001).

Conclusion: The frequency of malignancy found in patients with MPD diameter between 5-9mm and also in cysts 2.5cm in diameter suggests that there is space for discussion of reducing the cutoff for the diameter lesions were classified as at high risk for malignancy. Furthermore, the presence of vegetation within cysts larger than 2.5 cm has a high PPV for the presence of malignancy, validating the proposed consensus.

Disclosure of Interest: None declared

P0727 EXPRESSION OF HEDGEHOG SIGNALING PATHWAY IN PANCREATIC DUCTAL ADENOCARCINOMA (PDAC) AND CHRONIC PANCREATITIS (PC)

K Winter¹, J Strzelczyk², M Dzieniecka³, M Wągrowska-Danilewicz⁴, M Danilewicz⁴, E Małecka-Panas¹

¹Department of Digestive Tract Diseases, ²Department of General and Transplant Surgery, Medical University, ³Department of Clinical Pathomorphology, Polish Mother's Memorial Hospital, ⁴Department of Nephropathology, Division of Morphometry, Medical University, Lodz, Poland

Contact E-mail Address: katarzyna.winter@vp.pl

Introduction: The involvement of the Hedgehog pathway in pancreatic carcinogenesis has been suggested. Hedgehog signaling molecules, such as Sonic hedgehog (Shh), Smoothened (Smo) and Glioblastoma transcription factor 1 (Gli1) are proposed as biomarkers for cancer detection and prognosis.

Aims & Methods: The aim of the study was to evaluate the Hedgehog signaling pathway molecules, α smooth muscle actin (αSMA) and Ki67 in patients with PDAC and CP.

We enrolled 114 patients undergoing pancreatic resection: 83 with PDAC and 31 with CP. Normal control pancreatic tissue was obtained from autopsy material from 21 patients. The immunoexpression of Shh, Smo, Gli1, αSMA and Ki67 were detected in tissue specimens by immunohistochemistry (Abcam antibodies, GB). The intensity and extend of staining of Shh, Smo, αSMA were recorded semi-quantitatively and for nuclear expression of Gli 1 and Ki67 labeling index was calculated.

Results: Mean Shh staining score in PDAC was: 2.24 (+0.57), which was significantly higher than in CP patients: 1.17(+0.25) and in control group: 0.79(+0.34) (p=0.000). Smo protein expression was 2.62(+0.34) in PDAC, 1.21(+0.23) in CP and 0.94(+0,15) in control group (p=0.000). Likewise Gli1 protein expression was higher in PDAC: 1.74(+0.74) than in CP: 1.15(+0.72) and in control group: 1(+0) (p=0.000). In addition, Shh and Smo immunoreactivity in CP was significantly higher than in the control group (p=0.024; p=0.007 respectively). Significant correlation was found between immunoexpression of Shh, Gli and Ki67 in PDAC group (r=0.379; r=0.28, respectively; p < 0.05).

Conclusion: Presented findings support the hypothesis on the role of Hedgehog pathway in pancreatic carcinogenesis as well as cell hyperproliferation in CP.

Disclosure of Interest: None declared

P0728 POOR SURVIVAL IN PANCREATIC MALIGNANCY ASSOCIATED WITH TROPICAL PANCREATITIS. IS IT A BIOLOGICALLY DIFFERENT DISEASE?

K. B. Leena¹, K. T. Shenoy²

¹Senior Research Manager, Population Health and Research Institute, Trivandrum, ²Gastroenterology, Sree Gokulam Medical College and Research Foundation, Venjaramoodu, India

Contact E-mail Address: drleenakb@yahoo.com

Introduction: Malignancy in tropical pancreatitis is associated with high chance of mortality and has higher rates of hepatic and or distant metastasis. In a prospective cohort with pancreatic malignancy, we studied the tumor size and survival.

Aims & Methods

Aims: To evaluate the operability, risk factors and survival of pancreatic malignacy in tropical pancreatitis.

Methods: In this prospective study, 1480 subjects with tropical pancreatitits were studied in a tertiary referral centre attached to Trivandrum Medical College in S India recruited between January 1980 and March 2006. On follow up, 164 developed malignancy. The diagnosis was estalished by CT/ MRI and MRCP followed by either FNAC pancreas or at surgical resection. Abdominal pain, diabetes and duration, alcohol abuse, tobacco smoking were evaluated in detail. Univariate analysis, Cox Proportional Hazard regression and Kaplan Meir Survival curves were plotted and analysed.

Results: Pancreatic malignacy occured at an younger age of 45 ± 12.4 years. The tumor was confined to head region in 130 subjects and tail and or body in the rest. Mean size was 4.2 cms and lymph node metastasis was present in 60%. 38 percent had hepatic/ distant metastasis and were inoperable. CA 19-9 level was over 1000 units in 80%. Duration of diabetes and abdominal pain didnot affect survival.The relative risk of mortality for: age over 50 was 4.97 (95% CI 3.7-6.67); for smoking 1.39 (95% CI 1.01-1.89). KM survival probability were 0.55 (95% CI 0.42-0.66) at 3 months; 0.24 at 6 months and 0.13 at 9 months.

Conclusion: The survival in pancreatic malignancy associated with tropical pancreatitis is poor and the biological behaviour is different; there was high regional and distant metastasis.

Disclosure of Interest: None declared

P0729 IS SCREENING FOR PANCREATIC CANCER IN HIGH-RISK GROUPS COST-EFFECTIVE?

M. T. Joergensen^1,*, A.-M. Gerdes², J. Soerensen³, O. Schaffalitzky de Muckadell⁴, M. B. Mortensen⁵

¹Department of Medical Gastroenterology and hepatology, Odense University Hospital and Vejle sygehus, Odense, ²Department of Clinical Genetics, Juliane Marie Centret, Rigshospitalet, Copenhagen, ³CAST, University of Southern Denmark Odense, ⁴Department of Medical Gastroenterology and hepatology, ⁵Department of Surgery, Odense University Hospital, Odense, Denmark

Contact E-mail Address: maiken.t.joergensen@rsyd.dk

Introduction: Pancreatic cancer (PC) is the fourth leading cause of cancer death worldwide, symptoms are few and diffuse, and when the diagnosis has been made only 10-15% would benefit from resection [1]. Surgery is the only potentially curable treatment for PC, and the prognosis seems to improve with early detection [2]. A hereditary component has been identified in 1-10% of the PC cases [3]. To comply with this, screening for PC in high-risk groups with a genetic disposition for PC has been recommended in research settings [4].

Aims & Methods: Between January 2006 and February 2014 31 patients with or with a disposition for HP and 40 first-degree relatives of patients with FPC were screened for development of PDAC with yearly endoscopic ultrasound and fine needle aspiration when needed. Total pancreatectomy was performed when 1) PDAC 2) PanINIII or 3) Main-duct IPMN was verified by histology. The cost-effectiveness of screening in comparison with no-screening was assessed by the ICER.

Results: By screening the FPC group we identified 2 patients with PDAC who were treated by total pancreatectomy. One patient is still alive, while the other died after 7 months due to cardiac surgery complications. The cost per PDAC identified was 132.899 US$, the cost per life-year saved was 37.994 US$ and the cost per QALY gained was 50.329 US$. Stratified analysis of patients with HP and FPC provided ICERs of 47.156 US$ vs. 35.493 US$ per life-year and 58.647 US$ vs. 47.867 US$ per QALY. Including only PDAC related death changed the ICER to 31.722 US$ per life-year and 42.128 US$ per QALY. The ICER for patients with FPC was estimated at 28.834 US$ per life-year and 38.785 US$ per QALY.

Conclusion: With a threshold value of 50.000 US$ per QALY this screening program appears to constitute a cost-effective intervention although screening of HP patients appears to be less cost-effective than FPC patients. These results are sensitive to appropriate stratification of the patients and the effectiveness of the treatment modalities offered. Both screening and surgery should be performed in specialized, research-based centres with many patients and a dedicated multidisciplinary approach and expertise.

Disclosure of Interest: None declared

P0730 EUS-GUIDED INTRATUMORAL INJECTION OF CHST15 DSRNA FOR UNRESECTABLE PANCREATIC CANCER: AN INVESTIGATOR-INITIATED TRIAL

M. Nishimura¹

¹Department of Gastrointestinal Endoscopy, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan

Contact E-mail Address: nimakoto@gmail.com

Introduction: The glycosaminoglycan chondroitin sulfate E (CS-E) is known to promote tumor invasion by cleaving CD44 on pancreatic cancer cells. Interference with CS-E has been shown to inhibit tumor invasion and metastasis in nonclinical studies. CS-E is upregulated in pancreatic cancer tissue and its biosynthesis is mediated by specific enzyme carbohydrate sulfotransferase 15 (CHST15). CHST15 mRNA is reported to be upregulated and to correlate with poor prognosis in several types of cancer. We have shown that synthesized CHST15 dsRNA can inhibit the expression of CHST15 mRNA in human pancreatic cancer cells in vitro. In this study, we conducted an investigator initiated trial of CHST15 dsRNA through EUS-guided intratumoral injection in patients with unresectable pancreatic cancer.

Aims & Methods: Primary outcome measures were safety, feasibility, and tolerability. Secondary outcome measures were response in tumor size, overall survival (OS) and disease-free survival. Histopathologically, tumor specimens were also evaluated with CHST15 immuno-stain before and 1 month after injection.

Results: A total of five stage IV pancreatic cancer patients with a median age of 75.8 years (male: female= 3:2) were enrolled. Four of them had undergone standard chemotherapy including gemcitabine or S-1 regimen, and the other patient refused chemotherapy. For all patients, a total of 16 ml (250nM) of dsRNA was successfully injected into the tumor under EUS guidance using a 22 gauge needle without related adverse events. Mean tumor size changed from 29.0 (21-39) mm to 29.6 (23-45) mm in diameter one month after the first injection. Histopathologically, all patients (100%) were CHST15 positive in the primary specimen, and one patient’s specimen revealed CHST15 weakness one month after the first injection, suggesting the effectiveness of dsRNA injection.

Conclusion: This was the first-in-patient trial of EUS-guided injection of dsRNA against glycogene in unresectable pancreatic cancer in the world. A single-dose administration of CHST15 dsRNA showed no drug-related adverse effects at the tested concentration. High safety and feasibility were demonstrated, which will contribute to further clinical trials investigating this anti-tumor agent.

Disclosure of Interest: None declared

TUESDAY, OCTOBER 27, 2015   09:00-17:00

ENDOSCOPY AND IMAGING II – HALL 7__________

P0731 PER ORAL ENDOSCOPIC PYLOROMYOTOMY AFTER SUB-MUCOSAL TUNNEL FOR THE TREATMENT OF REFRACTORY GASTROPARESIS: A CLINICAL CASE SERIES

J.-M. Gonzalez¹, A. Benezech¹, V. Lestelle¹, V. Vitton¹, M. Barthet¹

¹Gastroenterology, AP-HM, North Hospital, Marseille, France

Contact E-mail Address: jmgonza05@yahoo.fr

Introduction: Gastroparesis is a motility disorder affecting 4% of the population with symptoms related to pathological gastric emptying. Therapeutic options remain limited with many patients refractory to the medical treatment. 2 series reported the effectiveness of laparoscopic pyloroplasty. Recently, endoscopic per oral pyloromyotomy after tunnel creation (G-POEM) has been attempted (3 cases: US, Brazil and our team) with excellent results.

Aims & Methods: Five patients, 3 men and 2 women, with mean age of 58 years old [42 – 76], were managed in our center for refractory gastroparesis. Two were due to diabetes, two were post operative consequences (Heller), and one idiopathic. All the patients underwent a G-POEM procedure after multidisciplinary discussion and giving informed consent. Four of them have had a pre-operative gastric emptying scintigraphy. The procedures were performed by an endoscopist expert in esophageal POEM, on patients under general anesthesia, intubated and in supine position. We used a large operating channel gastroscope (Pentax, Japan) with CO₂ and a Triangle Tip knife (Olympus, Japan). The steps of the procedure were: 1/ mucosal incision after submucosal injection (posterior wall, 5cm upstream the pylorus); 2/ Tunnel creation by dissection (Swift Coag 35 W); 3/ Pyloric 3cm complete incision; 4/ Closure of the mucosal flap. An antibiotic prophylaxis and PPI were administrated daily. They were followed-up clinically at 1 month and associating a gastric emptying scintigraphy at 3 months.

Results: A complete procedure could be performed on all the patients but one (4/5). The failed patient had a fibrotic stomach and was mistakenly performed with a regular channel scope resulting in difficult access to the pylorus. The mean duration was 100 minutes without per- or post-operative complication. All the patients could drink at POD 2, eat gradually at POD 3, and were discharged at POD 6. The patients with technical success reported a mean improvement of quality of life of 73% [65-90%] and of gastric emptying symptoms of 60% at 1 month, persisting at 3 months. Regarding the scintigraphy, the baseline evaluation showed a mean half gastric emptying time (HGET) of 139 min [104-188] and a mean residual percentage at hour 4 (RPH4) of 25% [6-45%]. After the G-POEM, the mean HGET and RPH4 were normalized, decreasing to 81 min [77-85, p=005] and 4% [1-9, NS], respectively.

Conclusion: Endoscopic pyloromyotomy with the G-POEM technique is feasible, reproducible, and safe. This approach seems effective clinically in terms of quality of life and specific symptoms, which was confirmed by the scintigraphy. A prospective study will soon start in our department to clearly confirm its great potential on patient with refractory severe gastroparesis.

Disclosure of Interest: None declared

P0732 PREDICTORS OF MORTALITY IN CAUSTIC INGESTION: A SINGLE, TERTIARY CENTER STUDY

J. M. Libuit¹, G. C. Carpio¹, S. Macalindong¹, J. P. Ong¹

¹Medicine, Philippine General Hospital, Manila, Philippines

Contact E-mail Address: jefflibuitmd@gmail.com

Introduction: Caustic ingestion, whether accidental or intentional, causes severe injury to the esophagus and the stomach, and may be associated with significant morbidity and even mortality. The severity of caustic injury depends on the following factors: corrosive properties of the ingested substance, amount, concentration, and physical form of the agent and duration of contact with the mucosa.

Aims & Methods: This is a retrospective cross-sectional study which included all adult patients who ingested caustic agents who were admitted at the Philippine General Hospital Acute Care Unit from January 1, 2008 to December 31, 2012. This study aimed to determine the predictors of mortality; determined the incidence of caustic ingestion and surgical and mortality rates; and characterized patients admitted for caustic ingestion.

Results: There were 303 cases of caustic ingestion admitted over a five-year study period. The mean age was 36 ± 13 years. There were slightly more male patients. Ingestion of acidic corrosive agents was more common than alkaline substances Majority were intentional in nature. The average amount of ingested substance was 74.9 ± 84.9 ml. Psychiatric disorder was the most commonly identified co-morbidity and was the only co-existing illness recognized among patients who expired. The most common symptoms were vomiting and abdominal pain. Among 154 patients who underwent esophagogastroduodenoscopy, half had mild (Zargar grades 1-2b) mucosal injury. One-third had severe (Zargar grade 3) mucosal injury. Around 10% had no signs of mucosal injury. Metabolic acidosis and leukocytosis were common laboratory findings. There were 13 cases of perforation (perforation rate of 4.5%). Surgery was performed in 56 (19.2%) patients. There were 23 recorded cases of death (8.1% mortality rate). Only metabolic acidosis, presence of a psychiatric disorder, need for surgical intervention, and presence of documented perforation were significantly different between patients who expired and who survived. On univariate analysis, presence of psychiatric abnormality did not show significant association with mortality (Table 1). Multivariate analysis revealed that surgery was the most consistent predictor of mortality. Perforation had no effect in the absence of metabolic acidosis.

TABLE 1.

Univariate Analyses on the Effects of Metabolic Acidosis, Presence of Psychiatric Disorder, Need for Surgery, and Perforation on Mortality

Clinical /Parameter	Odds Ratio	95% CI	P-value
Metabolic Acidosis	10.6	2.17, 76	0.006
Presence of Psychiatric Disorder	4	0.55, 20.4	0.108
Need for Surgery	13.3	3.9, 44.6	< 0.001
Perforation	22.2	8.3, 70.4	< 0.001

Conclusion: The clinico-demographic profiles of the adult subjects, distribution of severity of mucosal injury, all-cause mortality rate and surgery rate in this study are similar to the other publication. Patients with metabolic acidosis on admission, undergoing surgical intervention, and with perforation are at higher risk of death. Among these, institution of surgical intervention was the most consistent predictor of mortality. We recommend that these patients be closely monitored during their hospital stay in order to lower the possibility of mortality.

Disclosure of Interest: None declared

P0733 ENDOSCOPIC PREDICTORS FOR UNDIFFERENTIATED HISTOLOGY IN DIFFERENTIATED GASTRIC NEOPLASMS PRIOR TO ENDOSCOPIC RESECTION

J. M. Choi¹, S. G. Kim¹, H.-J. Yang¹, J. H. Lim², J. Choi¹, J. P. Im¹, J. S. Kim¹, H. C. Jung¹

¹Internal Medicine, Seoul National University Hospital, ²Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea

Contact E-mail Address: skyjimin@hanmail.net

Introduction: Endoscopic submucosal dissection (ESD) has been widely accepted as an established treatment modality for gastric neoplasms. With regard to patient selection for ESD, an exact histologic diagnosis before treatment is essential. However, there is often a discrepancy between results from endoscopic forcep biopsy and resected specimen.

Aims & Methods: We aimed to identify endoscopic predictors for undifferentiated histology in differentiated gastric neoplasms prior to endoscopic resection. Medical records of the patients who underwent ESD for biopsy-proven differentiated gastric neoplasms at Seoul National University Hospital between July 2005 and July 2014 were retrospectively reviewed. The lesions were divided into two groups based on the histologic result of ESD: differentiated adenocarcinoma (DA group) and undifferentiated histology (UDH group). The discordant rate, clinicopathologic characteristics and endoscopic factors were analyzed.

Results: A total of 1,641 early gastric cancers from 1,615 patients were included. Of these, 1,556 (94.8%) were diagnosed as DA and 85 (5.2%) as UDH. The mean age was significantly lower and number of women was higher in the UDH group than in the DA group. On multivariate analysis, age <65 years (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.10–2.80), female sex (OR 3.19, 95% CI 2.00–5.08), endoscopic size >10 mm (OR 1.81, 95% CI 1.12–2.92), depressed type (OR 2.85, 95% CI 1.56–5.21), nodularity (OR 2.83, 95% CI 1.59–5.05), and whitish discoloration (OR 19.64, 95% CI 6.98–55.25) were independent predictors.

Table 1.

Multivariate analysis of clinicopathologic and endoscopic characteristics associated with undifferentiated histology in endoscopic submucosal dissection

Characteristics	OR (95% CI)	P value
Age
≥65	1.00 (reference)
<65	1.75 (1.10 – 2.80)	0.019
Sex
Male	1.00 (reference)
Female	3.19 (2.00 – 5.08)	< 0.001
Endoscopic size
≤10 mm	1.00 (reference)
>10 mm	1.81 (1.12 – 2.92)	0.016
Macroscopic type
Elevated	1.00 (reference)
Flat	1.49 (0.70 – 3.14)	0.298
Depressed	2.85 (1.56 – 5.21)	0.001
Gross morphology
Ulcer	1.97 (0.76 – 5.07)	0.161
Erosion	0.71 (0.41 – 1.26)	0.241
Whitish discoloration	19.64 (6.98 – 55.25)	< 0.001
Nodularity	2.83 (1.59 – 5.05)	< 0.001

Conclusion: Female sex, age <65 years, large endoscopic size, depressed morphology, surface nodularity, and whitish discoloration were predictors for UDH. Meticulous attention should be paid to the lesions with these endoscopic predictors for determining the risk of UDH prior to endoscopic resection.

Disclosure of Interest: None declared

P0734 CLINICAL OUTCOMES OF NO RESIDUAL DISEASE IN THE SPECIMEN AFTER ENDOSCOPIC RESECTION FOR GASTRIC NEOPLASMS

J. M. Choi¹, S. G. Kim¹, H.-J. Yang¹, J. H. Lim², J. Choi¹, J. P. Im¹, J. S. Kim¹, H. C. Jung¹

¹Internal Medicine, Seoul National University Hospital, ²Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea

Contact E-mail Address: skyjimin@hanmail.net

Introduction: Endoscopic resection (ER) has been widely accepted as a curative treatment strategy for early gastric cancer and gastric adenoma. However, no residual disease (NRD) can be found in the specimen after ER of biopsy-proven gastric neoplasm.

Aims & Methods: This study aimed to evaluate the endoscopic and pathologic characteristics of patients with NRD, and identify the cause and long-term prognosis. Medical records of patients who underwent ER for biopsy-proven gastric neoplasms at a single tertiary hospital between January 2005 and November 2014 were retrospectively reviewed. Patients whose post-ER histology was revealed as NRD were included in the study. Overall incidence, clinicopathologic characteristics, cause, and long-term prognosis were analyzed.

Results: NRD was detected in 138 (3.2%) of 4,318 cases of gastric neoplasms treated with ER. Mean endoscopic size of the initial lesion was 8.27 ± 6.73 mm; in 92 cases (66.7%), the lesion was located in the lower third of the stomach. Initial pathologic diagnosis was as follows: adenoma (n=108), carcinoma (n=26), and atypical gland (n=4). The causes of NRD were minute lesions removed by biopsy in 135 patients, pathologic misdiagnoses in 2, and localization error in 1. Local recurrence was detected in 5 patients (3.7%) with minute lesions during follow-up and treated with argon plasma coagulation (n=4) or re-ER (n=1). Synchronous (n=5, 3.7%) and metachronous gastric lesions (n=6, 4.4%) were also detected during follow-up.

Conclusion: The main cause of NRD was minute lesions, which might be completely removed by initial diagnostic biopsy; these cases showed a minimal rate of local recurrence and synchronous or metachronous gastric neoplasms. Careful follow-up is also mandatory for detection of residual disease.

Disclosure of Interest: None declared

P0735 ENDOSCOPIC FULL-THICKNESS RESECTION WITH DEFECT CLOSURE USING AN OVER-THE-SCOPE CLIP FOR GASTRIC SUBEPITHELIAL TUMORS

J. Guo¹

¹Endoscopy Center, Shengjing Hospital of China Medical University, Shenyang, China

Contact E-mail Address: guojt@sj-hospital.org

Introduction: Endoscopic full-thickness resection (EFTR) is a mini-invasive technique for gastric subepithelial tumors originating from the muscularis propria, which enables a full-thickness resection of tumors and can provide a complete basis for pathological diagnosis. Gastric fistula closure after EFTR is a challenge for endoscopists. In this study we introduced EFTR with fistula closure using the over-the-scope clip (OTSC) system for gastric subepithelial tumors originating from the muscularis propria.

Aims & Methods: Objectives: To evaluate the feasibility and safety of fistula closure with OTSC by a retrospective analysis on the cases of EFTR with defect closure using OTSC for gastric subepithelial tumors originating from the muscularis propria in our hospital.

Methods: The patients were selected who underwent EFTR for gastric subepithelial tumors originating from the muscularis propria (tumor diameter ≤2cm) in our hospital from October 2013 to March 2014. After a full-thickness resection of tumors, the OTSC was released to close the defect. The success rate of defect closure with OTSC was observed and the endoscopic follow-up was performed at 1 week, 1 month and 6 months after operation to check OTSC closure.

Results: Totally 23 patients were included into the study. The full-thickness resection rate of gastric tumors in the muscularis propria was 100% (23/23), the success rate of defect closure was 100%, and the average time of defect closure was 4.9 min (range: 2-12 min). All patients experienced no postoperative complications such as bleeding and perforation. The postoperative follow-up time was 1-6 months (mean: 3 months), and no OTSC detachment was found.

Conclusion: OTSC can be used to perform EFTR with defect closure for gastric tumors in the muscularis propria (tumor diameter ≤2cm). It is simple, convenient, safe and effective.

Disclosure of Interest: None declared

P0736 FINDINGS IN GASTROSCOPY WITH BIOPSY AS A PREDICTOR OF RESECTABILITY OF GASTRIC CANCER

J. J. Vila¹, A. Borda¹, I. *Fernández-Urién¹, J. Jiménez-Pérez¹, J. M. Zozaya¹, A. Guerra¹

¹Gastroenterology, Complejo Hospitalario De Navarra, Pamplona, Spain

Contact E-mail Address: abordamartin@yahoo.es

Introduction: Gastric cancer diagnosis is usually performed by gastroscopy with biopsies, but reports about its predictive value for cancer resectability are scarce.

Aims & Methods: To analyze endoscopy findings predictive value concerning resection possibilities with curative intention in gastric cancer.

264 gastric carcinomas, consecutively diagnosed by endoscopic biopsy, were retrospectively reviewed. Non operated cases due to causes not related to the tumor (age and/or comorbidities) were excluded. Thus, frequency of the following parameters were compared between resected and non resected cases: Size > 5cm, macroscopic type (Japanese classification of gastric carcinomas), Lauren histological subtype and differentiation grade (I-IV). The group of variables with p < 0.05 was considered as a predictive diagnostic test for resectability and its sensitivity (S), specificity (Sp), positive (PPV) and negative predictive value (NPV) and diagnostic accuracy (DA) were calculated.

Results: 154 patients were operated with curative intention. Of the rest, 11 were operated without resection and 62 were inoperable due to their tumoral stage. 37 inoperable cases were excluded for the statistical analysis because of their age and/or comorbidity. No significant differences in resectability were registered regarding tumoral location: p= 0.25 or histological type. Tumors <5cm showed a higher resectability rate: 88.2% versus 48.7%; [OR = 7.69; IC95% = (3.85-128.2); p = 0.000]. Carcinomas with an infiltrative component (ulcerated infiltrative-diffuse infiltrative) registered a lower resectability rate: 53% vs the rest: 73.9%.[OR = 2.51; IC95% = (1.32-4.77); p = 0.002]. According to the differentiation grade the resectability was: grade I-II (well-moderately differentiated) = 86% vs III-IV (poorly-undifferentiated) = 56.4% [OR = 5; IC = (2.38-111.1); p = 0.000]. If tumors <5cm, with no macroscopically infiltrative type and well-moderate differentiation grade were considered as positive diagnostic test for resectability we obtained a S = 0.80; Sp = 0.95; PPV = 0.98; NPV= 0,63 y DA = 0.84.

Conclusion: 1. Among all parameters which can be evaluated with a gastroscopy plus biopsies, size <5 cms, a macroscopically non infiltrative type and a well-moderate differentiation grade showed a significant predictive value for gastric cancer resectability with curative intention.

2. High specificity rate and positive predictive value were registered considering as a positive diagnostic test for resectability the presence of a tumor <5cm, with no endoscopic infiltrative component and with a well-moderate differentiation grade.

Disclosure of Interest: None declared

P0737 GENTAMICIN SUBMUCOSAL LAVAGE DURING PER ORAL ENDOSCOPIC MYOTOMY (POEM): IS IT NECESSARY?

J. Bayer¹, Z. Vacková¹, J. Špičák¹, H. Švecová¹, J. Martínek¹

¹IKEM, Prague, Czech Republic

Contact E-mail Address: busta-bayer@web.de

Introduction: Per oral endoscopic myotomy (POEM) is an evolving therapeutic modality for achalasia. According to the original Inoue´s technique, lavage with gentamicin (80 mg) into the submucosal tunnel before starting the myotomy has been practiced due to the fear of infection. Since the number of infectious complications during POEM has been negligible, several centers (including our own) discontinued the use of gentamicin. However, there is no data assessing the clinical utility of gentamicin lavage yet.

Aims & Methods: The aim of this study was to compare outcomes of patients who received gentamicin lavage vs. patients who did not.

A retrospective analysis of prospectively collected data. POEM was performed in 86 patients (median age 46). Before the procedure, all patients were given intravenously ceftriaxone 2 g and metronidazole 500 mg; ceftriaxone was further administered on POD 2 and 3. In 60 patients (69.8%), a lavage with 80 mg of gentamicin diluted in 10 mL of normal saline was performed into the submucosal tunnel before starting the myotomy (= group A). In 26 patients (30.2%), gentamicin lavage was not performed (= group B). The main outcome variables were CRP level, WBC level, infectious complications and postprocedural fever and pain.

Results: The treatment success at 12 months (defined as an Eckardt score <3) did not differ between the two groups (group A 98.3% vs. 100% group B). We did not experience any clinically significant infectious complications, such as mediastinitis, peritonitis or abscesses, in either group. In group A (with gentamicin), there was a trend for lower CRP levels and lower WBC count after POEM (POD 1, median with IQ range: CRP: 52.6 (34.8) mg/L vs. 68.2 (34.1) mg/L, p= 0.1; WBC: (10.9 (3.3) vs. 12.4 (3.7) (p= 0.05). Regarding all remaining parameters, we did not detect any differences between the two groups (group A vs. group B, median with IQR: RBC 4.2 (0.6) vs. 4.3 (0.7), Hb 129.5 (18) vs. 133 (22), length of hospitalization 2.0 (1) vs. 2.0 (0) days. The post POEM fever was present on POD 1 and/or POD 2 in 10% of patients in the group A and in 11.5% of patients in the group B (NS).

Conclusion: During POEM, submucosal lavage with gentamicin prior to myotomy does not seem to play a role in the prevention of clinically significant infectious complications, although the systemic inflammatory response may be decreased.

Disclosure of Interest: None declared

P0738 ENTERAL ACCESS FOR DUODOPA INFUSION: THE ROLE OF THE ENDOSCOPIST

J. Cheron¹, P. Eisendrath¹, D. Blero¹, O. Le Moine¹, J. Devière¹, E. Toussaint¹², A. Ballarin², D. Zegers De Beyl³, A. Van Gossum¹², M. Arvanitakis¹²

¹Gastroenterology Department, ²Nutrition team, ³Neurology Department, Erasme University Hospital, ULB, Brussels, Belgium

Contact E-mail Address: jcheron@ulb.ac.be

Introduction: In patients with advanced Parkinson's disease, the continuous delivery to the jejunum of levodopa/carbidopa (Duodopa) represents a new therapy, which results in less motor fluctuations than oral administration, but requires insertion of a percutaneous endoscopic gastrostomy with a jejunal extension (PEG-J). In this study, outcome of patients undergoing PEG-J placement for Duodopa infusion was analysed.

Aims & Methods: A prospective trial regarding Duodopa treatment is on-going in our institution. All patients had a nasojejunal tube placed initially to assess Duodopa efficiency and dosage, following by a PEG-J after 9 weeks, which was used exclusively for Duodopa infusion. We report the results (technical success, complication rate and outcome), regarding endoscopic management. Complications were defined as adverse effects that required specific treatment (surgery, endoscopy) and/or prolonged hospitalisation.

Results: 27 patients (17 men, median age: 64 (42-80)) were included for long-term Duodopa treatment requiring PEG-J placement, from June 2007 to April 2015. The nasojejunal tube (Freka intestinal tube CH15) was inserted under sedation (n=11) or general anaesthesia (n=16). This was performed either from the nasal route with a paediatric scope and the use of a guidewire (n=17), either with a standard scope and a biopsy forceps (n=10). No complications were noted. The PEG-J (Freka PEG CH15) was placed under general anaesthesia in all patients. The jejunal extension was inserted during the same procedure in the majority of the patients (n=25, 93%).

Complications (n=17) were reported in 12 patients (44%) including J-tube migration (n=4, during first 3 months after insertion), J-tube impaction in the jejunum (n=1), J-tube dysfunction (n=5), Buried Bumper Syndrome (n=2), duodenal ulcer (n=2), covered duodenal perforation (n=1), peritonitis (n=1), and jejunal perforation with duodenal fistula (n=1). Complications occurred after a mean follow-up of 17 months (0-54 months). All complications were managed successfully medically (n=3), by endoscopy (n=13), or by surgery (n=1).

The mean number of repeat endoscopy was 2.60 (0-9) (including scheduled procedures for tube replacement and procedures for complications management) during a mean follow-up of 51 months (1-94 months).

All patients responded well to Duodopa regarding neurological outcome. There were no mortalities related to nasojejunal tube or PEG-J during follow-up.

5 patients required PEG-J definitive removal because of cognitive defect (n=2), psychological trouble (n=1) and gastrointestinal complications (n=2, jejunal perforation with duodenal fistula; duodenal ulcer). This PEG-J withdrawal occurred after a mean follow-up duration of 27 months (1-72 months).

Conclusion: Placement of a PEG-J tube for Duodopa jejunal treatment in patients with advanced Parkinson’s disease is an effective and noninvasive technique but which carries a high risk of gastro-intestinal complications, probably linked to the overall fragility of these patients. Patients should be fully informed of procedure-related complications and should be followed-up accordingly in referral centres.

Disclosure of Interest: None declared

P0739 RECURRENCE OF ZENKER’S DIVERTICULUM IS MORE FREQUENT IN MEN WITH SEVERE SYMPTOMS

J. Brueckner¹, H. Messmann¹, S. K. Goelder¹

¹Gastroenterology, Klinikum Augsburg, Augsburg, Germany

Contact E-mail Address: juliane.brueckner@klinikum-augsburg.de

Introduction: Zenker’s diverticulum (ZD) is an illness of the middle-aged and elderly, with a 1.5-fold predominance in men. It develops over time through increased pressure at the Kilian triangle due to impaired relaxation of the upper esophageal sphincter. Nowadays, endoscopic treatment is well established offering various techniques. However, some 20 – 30 % of patients experience recurrence of symptoms after successful treatment. The objective of this study was to identify predictive factors for development of recurrence in order to optimize surveillance for patients at risk.

Aims & Methods: A patient cohort of 25 male and 21 female patients, mean age 67 years, with symptomatic ZD was retrospectively analyzed for pre-treatment differences between patients who experienced or did not experience recurrence. In this cohort 12 out of 47 patients experienced recurrence of symptoms. We examined descriptive factors such as sex, age, multimorbidity, prior treatment and altered local anatomy, as well as severity, duration and frequency of pre-treatment clinical symptoms and complications due to ZD.

Results: Most strikingly, we observed a higher pre-treatment prevalence of severe symptoms such as vomiting (frequency score 2.25 vs. 0.26; p< 0.01) and symptom-related insomnia (1.71 vs. 1.04, n. s.) in the recurrence group. Likewise, the dysphagia score was markedly higher (2.27 vs. 1.61, n. s.). Upon further stratification of the recurrence group by No. of sessions (2 or 3 sessions total), the patients with 3 sessions had even more pronounced symptoms. However, due to the small number of these cases there were no significances. Also, duration of symptoms was longer (24.1 vs. 19.6 months, n. s.) and weight loss was more pronounced (3.6 vs. 0.9 kg) in the recurrence group. Analysis of the descriptive factors showed more male patients in the recurrence group (80 % vs. 47 %; p < 0.05), whereas old age and multimorbidity did not show a relevant difference.

Conclusion: Male patients with a high dysphagia score and high frequency of severe symptoms are more likely to experience recurrence of symptoms from ZD and should be monitored more closely following successful endoscopic treatment.

Disclosure of Interest: None declared

P0740 EFFICACY OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR CANCER OF THE OPERATED STOMACH

J. Nishimura¹, J. Nishikawa¹, M. Nagao¹, S. Sasaki¹, M. Nakamura¹, S. Hashimoto¹, T. Okamoto¹, I. Sakaida¹

¹Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan

Contact E-mail Address: nishimuj@nagato-hp.jp

Introduction: Cancer can develop in the operated stomach after partial gastrectomy and in the reconstructed gastric tube after surgery for esophageal cancer. It is considered that endoscopic therapy is more safe and suitable for the early gastric cancer developed in such stomah than opration. To investigate the efficacy of endoscopic submucosal dissection (ESD) for cancer of the operated stomach.

Aims & Methods: Subjects were 669 gastric cancer patients who underwent ESD: 22 patients (23 lesions) had surgically altered gastric anatomy, whereas 647 patients (727 lesions) had normal gastric anatomy. In the altered gastric anatomy group, 13 patients, 6 patients and 3 patients had previously undergone distal gastrectomy, gastric tube reconstruction, and proximal gastrectomy, respectively. Rates of complete en bloc resection and curative resection were compared between the two groups. Influence of an anastomotic site and/or a suture line on ESD outcomes was examined in the altered gastric anatomy group.

Results: The rate of complete en bloc resection by ESD was 82.6% (19/23) in the altered gastric anatomy group and 92.3% (671/727) in the normal gastric anatomy group. The rate of curative resection and incident rates of complications were not significantly different between the groups. In the altered gastric anatomy group, the rate of complete en bloc resection was significantly lower when a lesion had spread across an anastomotic site and/or a suture line (P = 0.0372). Furthermore, duration of ESD was significantly longer (P = 0.0276), and resection efficiency was significantly lower (13 mm²/min, P = 0.0283), when treating lesions with an anastomotic site and/or a suture line than when treating isolated lesions.

Conclusion: Outcome of ESD for cancer of the operated stomach compares with that in normal stomach anatomy. Anastomotic site/suture line within a lesion influenced the ESD procedure.

Disclosure of Interest: None declared

P0741 METHYLENE BLUE CHROMOENDOSCOPY AND MAGNIFICATION ENDOSCOPY ARE NOT USEFUL FOR DIFFERENTIATING TYPES OF INTESTINAL METAPLASIA IN THE STOMACH

J. Wasielica-Berger¹, A. Pryczynicz², A. Kemona², A. Dabrowski¹

¹Department of Gastroenterology and Internal Medicine, ²Department of Pathomorphology, Medical University of Bialystok, Bialystok, Poland

Contact E-mail Address: jwasielica@o2.pl

Introduction: Intestinal metaplasia (IM) in the stomach is a precancerous state often presenting as foci. IM can be divided into complete and incomplete, the latter bears greater risk of malignant transformation. Methylene blue (MB) chromoendoscopy can detect IM in the stomach, but sensitivity of this method is low. We hypothesised that those two types of IM have different ability to absorb MB which may be the cause of false negative results of chromoendoscopy. Previous studies suggested that complete and incomplete IM in the stomach present with different mucosal surface pit patterns.

Aims & Methods: We aimed to check if absorption of MB depends from the type of IM and if mucosal pit pattern evaluation may be helpful to discern complete and incomplete IM in the stomach. 37 patients with previously diagnosed IM in the stomach underwent gastroscopy with 0.5% MB staining and evaluation of gastric mucosal pit pattern in magnification up to x115 (Olympus GIF Q160Z). Biopsies were collected from antrum and corpus of the stomach, separately from the areas that stained and did not stain with MB. If intestinal metaplasia has been found in H&E histology, it was further differentiated into complete and incomplete by histochemistry (Alcian Blue PAS pH 2,5).

Results: We collected biopsies from 127 areas (34 stained and 93 unstained). Intestinal metaplasia was found in 57 bioptates (44.9%). IM was found more often in specimens collected from areas stained with MB (27 out of 34 – 79.4%) than in specimens collected from areas that did not stain with MB (30 out of 93 – 32.3%), p < 0.001. MB chromoendoscopy had 47.4% sensitivity and 90.0% specificity in detecting IM. There was no difference in the frequency of positive MB staining between complete and incomplete IM (p=1.0). Comparing specimens containing IM collected from stained and unstained areas, the percentage of metaplastic cells in gastric mucosa was significantly higher in the first group (56.06%) than in the latter (28.17%, p < 0.001). IM was significantly less common in dot pit pattern (7.1%) than in tubular (38.9%, p < 0.05), villous (48.7%, p < 0.0005), foveolar (53.3%, p < 0.005) and cobblestone pit pattern (67.7%, p < 0.0005). The differences in frequency of IM between tubular, villous, foveolar and cobblestone pit patterns were not significant. The proportion of complete and incomplete intestinal metaplasia was similar in all pit patterns.

Conclusion: Positive MB staining and other than dot pit pattern correlate positively with the presence of IM. Positive or negative MB staining of metaplastic areas in the stomach may depend from percentage of metaplastic cells in gastric mucosa. Neither MB chromoendoscopy nor mucosal pit pattern evaluation are helpful in discerning complete and incomplete IM in the stomach.

Disclosure of Interest: None declared

P0742 IS THERE ANY VALUE OF ENDOSCOPY FOR GORD IN PATIENTS UNDER 45?

A. S. Solomon¹, K. Besherdas¹

¹Royal Free Hospital, Enfield, United Kingdom

Contact E-mail Address: kalpesh.besherdas@nhs.net

Introduction: For gastro-oesophageal reflux (GORD), upper endoscopy may be indicated in men older than 50 years with chronic GORD symptoms (symptoms for more than 5 years) and additional risk factors (nocturnal reflux symptoms, hiatal hernia, elevated body mass index, tobacco use, and intra-abdominal distribution of fat) to detect oesophageal adenocarcinoma and Barrett oesophagus. In addition, upper endoscopy is indicated in patients with heartburn and alarm symptoms, such as dysphagia, bleeding, anaemia, weight loss, and recurrent vomiting. However, upper endoscopy is not an appropriate first step in most patients with GORD symptoms and is indicated only when empirical PPI therapy for 4 to 8 weeks is unsuccessful. Furthermore, inappropriate use of upper endoscopy does not improve the health of patients, exposes them to preventable harms, may lead to additional unnecessary interventions and results in unnecessary costs with no benefit.

Aims & Methods: The aim of the study was to assess the findings at upper endoscopy in patients under 45 years endoscoped for reflux without alarm symptoms. A single centre retrospective analysis in a North London NHS Trust Hospital was performed. Patients endoscoped for reflux were identified using the Unisoft Endoscopy reporting software, across a period of 10 years (June 2005 - May 2015). Data from the patients’ electronic records were scrutinized if Barrett's was detected.

Results: A total of 1772 patients underwent upper endoscopy for reflux within the study period. 478/1772 patients were under 45 years of age. 124/ 1772 were found to have Barretts (7%). The age distribution was: under 45 years old: 16 patients (13%), 45-55 years: 20 patients (16%), 55-65 years old: 31 patients (24.8%), over 65: 57 patients (45.6%).

Out of the 478 patients under 45 undergoing endoscopy, 16 had Barrett’s (3%), and no patient had cancer of oesophagus/stomach. All the 16 patients with Barrett's under 45 years had a short segment Barrett's without dysplasia (8 patients with 1 cm, 7 patients with 2 cm maximal length, 1 patient with 3 cm maximal length.

Conclusion: From this study, no patients under 45 undergoing upper endoscopy for GORD had upper GI cancer and only 3% had Barrett's, all short segment (<3 cm). The yield of upper GI endoscopy in this group is very low. In austere times where supply of endoscopy is overstretched it is important not to overburden the service with unnecessary procedures. From this study, we do not advocate performing upper GI endoscopy in patients under 45 years of age with reflux without alarm symptoms.

Disclosure of Interest: None declared

P0743 PREDICTIVE FACTORS FOR INTRACTABILITY TO ENDOSCOPIC HEMOSTASIS IN THE TREATMENT OF BLEEDING GASTRODUODENAL PEPTIC ULCERS IN JAPANESE PATIENTS

K. Adachi¹, N. Ogasawara¹, Y. Yamaguchi¹, T. Yosimine¹, S. Gouji¹, N. Okaniwa¹, A. Tanabe¹, K. Yanamoto¹, H. Noda¹, Y. Ito¹, Y. Kondo¹, S. Izawa¹, M. Ebi¹, Y. Funaki¹, M. Sasaki¹, K. Kasugai¹

¹Department of Gastroenterogy, Aichi Medical University School of Medicine, Aichi, Japan

Contact E-mail Address: kazarchery@yahoo.co.jp

Introduction: Acute upper gastrointestinal (UGI) ulcers is a major cause of morbidity and mortality, as well as a common medical emergency. Endoscopic hemostasis is the first treatment for UGI ulcer, and it can avoid emergency surgery. However, it can be difficult to completely achieve in some patients, and excessive hemorrhage from UGI ulcers can be fatal. Endoscopic treatment of UGI bleeding has recently advanced along with the administration of high dose intravenous proton pump inhibitors. Despite improvements in endoscopic hemostasis and pharmacological therapies, UGI ulcers repeatedly bleed in 10% to 20% of patients, and those without early endoscopic reintervention or definitive surgery might be at a high risk for mortality. Therefore, determining which factors are involved in rebleeding after an initial endoscopic hemostasis is extremely important for patients with bleeding UGI ulcers. In addition, understanding the factors that contribute to intractable or in sufficient initial endoscopic hemostasis is needed to advance the management of such ulcers.

Aims & Methods: This study aimed to determine the risk factors for intractability to initial endoscopic hemostasis. We analyzed 558 patients who underwent emergency endoscopic for bleeding UGI ulcers within 24 hours of arrival at our hospital between April 2000 and October 2014. We retrospectively documented the patients’ backgrounds, and evaluated the ulcer location, size of exposed vessels on the bottom of the ulcer size, and Forrest bleeding patterns. To determine the factors involved in intractability to the initial endoscopic hemostasis, we compared patients whose bleeding UGI ulcers were successfully treated with the hemostasis with those who were intractable.

Results: Durable hemostasis was achieved in 477 patients (84.5%) by using initial endoscopic procedures. Seventy-six patients (14.6%) with Forrest types Ia, Ib, IIa, and IIb at the second look endoscopy were considered intractable to initial endoscopic hemostasis. Three patients (0.6%) who underwent emergency surgery because of failure to the initial endoscopic hemostasis and two patients (0.4%) who died right after the initial endoscopic hemostasis because of heart failure were also considered intractable to initial endoscopic hemostasis. Multivariate analysis indicated that smoking (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.16 to 3.24), shock on admission (OR, 2.68; 95% CI, 1.35 to 5.31), hemoglobin upon admission < 8.0 mg/dl (OR, 1.87; 95% CI, 1.02 to 3.42), serum albumin upon admission < 3.3 g/dL (OR, 2.05; 95% CI, 1.07 to 3.90), exposed vessels with a diameter of ≥ 2 mm on the bottom of ulcer (OR, 2.79; 95% CI, 1.65 to 4.72) predicted intractable endoscopic hemostasis, but Forrest types Ia was not the predictive factor of intractable endoscopic hemostasis.

Conclusion: Smoking, shock upon admission, hemoglobin < 8.0 mg/dL, serum albumin < 3.3 g/dL, and exposed vessels ≥ 2 mm on the ulcer bottom were identified as independent risk factors associated with initial intractable endoscopic hemostasis in patients with peptic UGI bleeds. Careful observation after initial endoscopic hemostasis is important for patients at a high risk for incomplete hemostasis.

Disclosure of Interest: None declared

P0744 PREDICTIVE FACTORS FOR OUTCOMES OF THROUGH-THE-SCOPE GASTRODUODENAL STENTING IN PATIENTS WITH GASTRIC OUTLET OBSTRUCTION; A LARGE MULTICENTER RETROSPECTIVE STUDY IN WEST JAPAN

K. Yamao¹, M. Kitano¹, T. Kayahara², E. Ishida², K. Minaga³, Y. Yamashita³, J. Nakajima⁴, M. Asada⁴, S. Okabe⁴, Y. Chiba⁵, H. Imai¹, M. Kudo¹, on behalf of Gastroduodenal Stenting Group in West Japan

¹Department of Gastroenterology and Hepatology, Kinki University Faculty of Medicine, Osakasayama, ²Department of Gastroenterology and Hepatology, Kurashiki Central Hospital, Okayama, ³Department of Gastroenterology, Japanese Red Cross Wakayama Medical Center, Wakayama, ⁴Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, ⁵Division of Biostatistics, Clinical Research Center, Kinki University Faculty of Medicine, Osakasayama, Japan

Contact E-mail Address: yamaken_volvo@yahoo.co.jp

Introduction: Gastric or pancreatobiliary cancer patients sometimes suffer from gastric outlet obstruction due to gastric or duodenal stenosis. Recently the through-the-scope gastroduodenal stenting for malignant gastric outlet obstruction has become more effective, but the gastroduodenal stenting is sometimes ineffective, and stent dysfunction and complications occur. Many previous studies have analyzed the clinical efficacy, but not much has been available on the predictive factors.

Aims & Methods: The purpose of the present study was to retrospectively evaluate the clinical effectiveness of the gastroduodenal stenting with malignant obstruction and to identify predictive factors associated with ineffectiveness, stent dysfunction and complications. Between March 2009 and March 2014, 278 patients who underwent through-the-scope gastroduodenal stenting at four tertiary medical centers in west Japan were analyzed retrospectively. Primary aim was to investigate predictive factors for the outcomes such as clinical ineffectiveness, stent dysfunction and complications. The ineffective group was defined as the group without achievement of the GOOSS of 2 or more and relief of symptoms of GOO after stenting on the day 7 after stenting.

Results: The mean age of patients was 71.7 ± 11.4 years old. The patient etiology was; pancreatic cancer in 121 (43.5%) and gastric cancer in 87 (31.3%). Technical success was achieved in 277 of 278 patients (99.6%). Clinical effectiveness was achieved in 242 of 277 patients (87.4%), while stenting was ineffective in 32 patients (11.6%) and 3 patient (1.1%) died within 7 days after stenting. Stent dysfunction (ingrowth, overgrowth, migration and others) occurred in 46 patients (16.6%) (16, 11, 11 and 8 patients, respectively). Complications (jaundice, bleedings, perforation and others) occurred in 54 patients (19.5%) (23, 15, 6 and 10 patients, respectively). Number of stenosis regions ≥ 3 (odds ratio 6.11; 95% CI 2.16-17.30; p < 0.01) and KPS ≤ 50 (odds ratio 6.63; 95% CI 2.89–15.20; p < 0.01) were the significant predictive factors for clinical ineffectiveness. KPS ≤ 50 (hazard ratio 4.10; 95% CI 1.80–9.32; p < 0.01) and covered stent (hazard ratio 2.05; 95% CI 1.07–3.93; p = 0.03) were the significant predictive factors for stent dysfunction. Type II stenosis (hazard ratio 40.94; 95% CI 2.58-649.90; P < 0.01), covered stent (hazard ratio 87.14; 95% CI 6.16-1232.81; P < 0.01) and ascites (hazard ratio 0.13; 95% CI 0.02-0.96; P < 0.05) were the significant predictive factors for stent migration. Deployment of 2 stents in the same session (hazard ratio 1554.78; 95% CI 12.63-191364.4; P < 0.01) was the significant predictive factor for perforation.

Conclusion: The gastrodudenal stenting tends to be ineffective in patients with poor performance status and long stenosis regions. Stent dysfunction occurs more frequently with using covered than uncovered stents and in patients with poorer performance status. Uncovered stent is recommended in case of type II stenosis and non-ascites. We have to pay attention to prevention of perforation during deployment of 2 stents.

Disclosure of Interest: None declared

P0745 ENDOSCOPIC ENBLOC RESECTION OF SUB EPITHELIAL TUMORS: A SINGLE-CENTRE STUDY

A. Bapaye¹, N. A. Dubale¹, K. Sheth¹, J. A. Bapaye¹, M. Kulkarni¹, R. Jajoo¹

¹Shivanand Desai Center for Digestive Disorders, Deenanath Mangeshkar Hospital and Research Center, Pune, India

Contact E-mail Address: amolbapaye@gmail.com

Introduction: Sub epithelial tumors (SETs) are soft tissue tumors arising from the sub mucosal or muscluaris propria layers of luminal organs. Enbloc resection of these lesions is desirable; often using surgical methods. Endoscopic techniques for resection of these lesions include endoscopic submucosal dissection (ESD) for lesions originating in the sub mucosal layer or endoscopic full thickness resection (EFTR) or submucosal tunneling endoscopic resection (STER) for lesions arising in the muscularis propria layer. This study describes our experience of endoscopic treatment of SETs.

Aims & Methods: Data of all consecutive patients undergoing endoscopic resection of SET in the period 2012 – 2014 was analyzed. All patients underwent pre procedure screening esophagogastroduodenoscopy (EGD) and endoscopic ultrasound (EUS) for assessment of the SET. One of following 3 procedures – ESD, EFTR or STER was performed for resection of the SET. ESD was performed for SET’s arising in sub mucosal layer whereas EFTR or STER was performed for lesions in the muscularis propria layer. All patients underwent follow up EGD at 4 - 6 weeks. Parameters recorded were – location of lesion, layer of origin, procedure performed (ESD, EFTR or STER), technical success, margin positivity on histology, complications and their management, final histopathology.

Results: 29 consecutive patients with sub epithelial tumors underwent endoscopic resection during study period. Mean age – 56 years (range 29-78) and 21 male patients. ESD was performed in 23 patients, EFTR in 4 and STER in 2. Location of SET’s was stomach (14), colon (6), duodenum (5), esophagus (3) and rectum (1). The mean area of sub epithelial tumors was 14.11 cm² (range 1-110). Histology was neuroendocrine tumors – 9, lipoma – 7, gastrointestinal stromal tumors – 6, leiomyoma – 5, ectopic pancreatic rest – 1 and duplication cyst – 1. Technical success of resection was 100%. 3 complications: perforation – 2 patients, 1 required surgery; bleeding – 1 patient, managed endoscopically. Histopathology of all specimens showed en-bloc excision with negative tumor margins.

Conclusion: Endoscopic en-bloc resection using ESD, EFTR or STER is a safe and effective therapy for SETs. Pre procedure EUS must be used to detect the layer of origin of SET. Based on EUS findings, the appropriate excision procedure can be selected.

Disclosure of Interest: None declared

P0746 PREDICTIVE FACTORS FOR LYMPH NODE METASTASIS AND LONG TERM OUTCOMES IN NON-CURATIVE PATIENTS WITH EARLY GASTRIC CANCER AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION

K. Nakamura¹, H. Kinugasa¹, K. Miyahara¹, M. Nakagawa¹

¹Internal Medicine, Hiroshima City Hospital, Hiroshima, Japan

Contact E-mail Address: kami_hi_koki@yahoo.co.jp

Introduction: Endoscopic submucosal dissection (ESD) is now widely employed and accepted in Japan as a less invasive treatment for early gastric cancer.

Aims & Methods: Endoscopic submucosal dissection (ESD) for gastric cancer has been familiarized broadly and rapidly. However risk factors and long-term outcomes in patients with non-curative resection after ESD remain to be elucidated. We evaluated predictive factors for lymph node metastasis (LNM) and long-term outcomes for these patients.

We analyzed 859 patients with early gastric cancer (1074 lesions) who underwent endoscopic submucosal dissection (ESD) from June 2001 through August 2011 in Hiroshima Citizens Hospital. Among 128 patients of non-curative resection, pathological factors have been analyzed. Ninety-nine patients (group A) have undergone an additional surgical gastrectomy with lymph node dissection and 29 patients (group B) have received no additional surgical gastrectomy due to their comorbidities. Seven hundred thirty one patients have had curative resection (group C). We have revealed risk factors for LNM and compared long-term outcomes in three groups.

Results:

The incidence of LNM was 8% (8/99) in group A. Pathological factors such as size, histology (pure differenced type, dominant type, pure undifferenced type), depth of submucosal invasion, ulceration, lymphatic involvement (LI), and venous involvement (VI) were examined for LNM. Decision tree analysis showed that the highest LNM risk combination was LI and ulceration. The frequency of LNM was 31% (3/9) in the patients LI and ulceration. Univariate analysis revealed that LI was only significant prognostic factor (p = 0.005). Kaplan-Meier demonstrated that there was a significant difference of group A and Group B (p = 0.0002) to group B and group C (p = 0.005).

Conclusion: LI was a only risk factor for LNM in patients with non-curative resection after ESD and additional surgical gastrectomy with lymph node dissection was recommended to them if possible.

Disclosure of Interest: None declared

P0747 CREATING AND ASSESSING EX-VIVO MODELS FOR SIMULATION ENDOSCOPIC TRAINING

I. Chizhikova¹, A. Ivanov¹, K. Petrova¹, E. Fedorov²

¹Training Center of Innovative Medical Technologies, ²Pirogov Russian National Research Medical University (RNRMU), Moscow, Russian Federation

Contact E-mail Address: i.o.tsukurova@gmail.com

Introduction: While virtual reality and plastic models are essentially similar for all training centers, ex vivo models are centers’ proprietary work, making it impossible for a student to assess the quality of a center’s model before taking the course. At the same time, lack of standards in the area of ex-vivo modelling directly affects the quality of trainings provided. In view of this, standards must be set to maximize the quality of ex-vivo models, both in terms of the organ and pathology representation and imitation of surgical manipulations.

Aims & Methods: To optimize the process of creation of ex-vivo models (illustrated with the example of the gastrointestinal hemorrhage model), we have developed the following methods:

1. Organ modeling: A) To ensure the stomach integrity, we recommend forming an artificial gastroesophageal sphincter imitation from polymers. B) To preserve the natural colour of the mucous membrane, we recommend treating it with NaCl isotonic solutions and storing the abdominal organs in a 20% ethanol, 10% glycerine solution, at -10 to -15 C.

2. Pathology modeling: A) To simulate Forrest I arterial hemorrhage, we recommend using a pulse pump, and a drip set to imitate a vein hemorrhage. B) We recommend using the vessels: animal’s own spleen artery and vein to imitate the vascular wall condition for this pathology.

3. Surgical manipulations imitation: A) The model supports the whole range of surgical techniques owing to the properties of the mucous membrane treatment solution and the natural properties of the animal’s vessels, which ensure good contact between the tissue and a plate electrode, and adequate electrocoagulation. B) To provide access to the abdominal organs, we recommend forming a polymer port in the upper esophagus, wide enough in diameter to the surgical tools to be used. C) To create a model that would support several types of gastrointestinal hemorrhage, we recommend modeling up to 20 Forrest Ia/b bleeding points in the organ’s wall.

Results: Based on four years of surgical gastroenterology work at the Training Center and on the feedback received individually and through polls from RNRMU professors, our international partners (including World Endoscopy Organization (WEO) experts) and students, we developed a set of performance criteria for ex-vivo models for each type of training.

Abstract number: P0747 Ex-vivo Model Assessment Chart: Gastrointestinal Hemorrhage

Criteria		Not achieved	Partially achieved	Fully achieved
Organ modeling	Organ integrity
Mucous membrane of natural color, with changes corresponding to the simulated pathology
Pathology modeling	Hemorrhage intensity true to type
Vessel wall condition
Surgery simulation	Supporting the whole range of surgical techniques
	Ease of access
Model supporting several types of hemorrhage

Conclusion: Based on these criteria, the key requirements to each ex-vivo model were identified and have been implemented in a targeted manner.

This paper exemplifies successful use of feedback from simulation training students to find solutions to the key problems of biomodelling.

Disclosure of Interest: None declared

P0748 CLINICAL OUTCOME IN PATIENTS TREATED WITH A NEWLY-DESIGNED SEMS IN CERVICAL ESOPHAGEAL STRICTURES AND FISTULAS

L. Poincloux¹, C. Sautel¹, O. Rouquette¹, M. Goutte¹, B. Pereira², G. Bommelaer¹, M. Dapoigny¹, A. Abergel¹

¹Digestive Disease, NHE - CHU of Clermont-Ferrand, ²Biostatistics Unit, DRCI, GM - CHU of Clermont-Ferrand, Clermont-Ferrand, France

Contact E-mail Address: lpoincloux@chu-clermontferrand.fr

Introduction: Using a self-expandable metallic stent (SEMS) in the cervical esophagus is controversial due to increased risk of complications. Here we assessed a new type of SEMS purpose-designed for the cervical esophagus area.

Aims & Methods: This study included patients with malignant or benign stenosis within 4 cm distance of the upper esophageal sphincter (UES) who underwent placement of an SEMS with a shorter proximal funnel (Niti-S Esophageal Covered Stent—Cervical-type, NSCSC), Taewoong Medical). Main outcome measures were functional outcome, tolerance, complications, recurrent dysphagia and survival.

Results: 37 patients had a NSCSC placed between April 2008 and June 2013 for esophageal stenosis (20 malignant=20, benign=17), 5 with associated tracheoesophageal fistula. Average distance between UES and upper taper of the stenosis was 1.86 ± 1.27 cm. Median follow-up was 150 days. Dysphagia improved in 27/37 cases (73%). Short-and long-term tolerance without needing stent removal was 92% and 82%, respectively. Complication rate was 59% (22/37): 32% (n=12 patients) major complications (fistula (3), perforation (3), aspiration pneumonia (5), laryngeal dyspnea (2) and bleeding (1)), and 27% (n=10 patients) pain (7) or dysphonia (3). 84% of major complications occurred after 49 days. Multivariate analysis found a higher risk of major complications in cases of benign stenosis (p=0.04). Recurrent dysphagia occurred in 15 (40%) patients due to obstruction (7) or migration (8).

Conclusion: NSCSC placement in the cervical esophagus effectively palliates dysphagia and is well-tolerated, but carries a high rate of complications. It does not seems to be less morbid than standard SEMS in this indication. The use of this device in benign strictures beyond six weeks is not recommended.

Disclosure of Interest: None declared

P0749 WHEN TO DRIVE SAFELY AFTER SEDATED ENDOSCOPY: A PROSPECTIVE PILOT STUDY ACCESSING THE DRIVING SKILLS RECOVERY AFTER ENDOSCOPIC SEDATION BY DRIVING SIMULATOR

L. Peng¹, Z. yuanlin¹

¹Department of Gastroenterology, Beijing Friendship Hospital,Capital Medical University, Beijing, China

Contact E-mail Address: 15011299045@163.com

Introduction: Patients after endoscopic sedation were recommended not driving in 24 hours.

Aims & Methods: Assessing patients driving skills recovery after endoscopic procedures with propofol sedation to determine when to drive safely. Outpatients range in age from 20 to 70 years old and hold legitimate licenses. Volunteers were recruited to have a gastroscopy or colonoscopy under intravenous anesthesia with propofol, and measured driving ability by driving simulator before, and 2h, 4h after endoscopy. Meanwhile, blood samples were collected respectively before, and 2h, 4h after endoscopy for propofol concentration, which was determined by High Performance Liquid Chromatography. Driving simulation scenes were designed as low, moderate and high risk. The low risk scene simulated S curve driving, the moderate risk scene evaluated overtaking ability, and the high risk one assessed emergency collision avoidance capacity.

Results: Thirty volunteers met the inclusion criteria and participated in preoperative driving simulation, but eight of them had symptoms of dizziness, nausea or vomiting in the driving simulation test and were excluded from the study. The rest twenty two cases completed preoperative driving simulation test, but four of them refused the next gastrointestinal endoscopy. Eventually, eighteen cases completed gastroscopy or colonoscopy with propofol sedation, the driving simulation and blood collection 2h, 4h after endoscopy. Repeated measures was used for analyzing the variables of low risk, medium risk and high risk driving scenes. In low risk S curve scene, average acceleration (cm/s2) before endoscopy, 0.016 ± 0.010 VS 2h after endoscopy, 0.029 ± 0.016, P=0.001; the average lane deviation (cm) before endoscopy, 42.50 ± 16.91 VS 2h after endoscopy, 53.80 ± 18.85, P=0.014; the maximum lane shift (cm) before endoscopy, 113.70 ± 31.91 VS 2h after endoscopy, 157.00 ± 62.27, P=0.024; the times of deviating from pathway before endoscopy, 0.83 ± 1.65 VS 2h after endoscopy, 2.06 ± 1.80, P= 0.022. In moderate risk scene and emergency collision avoidance high risk scene, there were no significant differences between before endoscopy and 2h after endoscopy. All variables of low, moderate and high risk scenes between before endoscopy and 4h after endoscopy, were no significant differences. The average blood concentration of propofol 2h after endoscopy was 0.81 ± 0.40 ug/ml, and propofol blood concentrations of blood samples collected 4h after endoscopy were below the limit of detection.

Conclusion: Subjects driving ability 2h after endoscopy was not recovered to baseline completely, but being fully restored 4h after endoscopy. Propofol had a certain impact on driving ability 2h after endoscopy.

Disclosure of Interest: None declared

P0750 ENDOSCOPIC CLOSURE OF GASTRIC DEFECTS RESULTING FROM ENDOSCOPIC FULL-THICKNESS RESECTION BY APPLICATION OF NOVEL ENDOLOOPS AND METALLIC CLIPS, USING A SINGLE-CHANNEL SCOPE: A MULTICENTER CLINICAL STUDY

S. Dongtao¹, L. Rui¹, C. Weichang¹, Z. Deqing¹, Z. Lei², G. Rui², Y. Ping³, W. Xudong⁴, W. Xudong⁴

¹Department of Gastroenterology, the First Affiliated Hospital of Soochow University, Soochow, ²Department of Gastroenterology, Hospital of Donghai County, Lianyungang, ³Department of Gastroenterology, the First Affiliated Hospital of Xinjiang Medical University, Urumchi, ⁴Department of Gastroenterology, the First People's Hospital of Yancheng, Yancheng, China

Contact E-mail Address: 210326031@suda.edu.cn

Introduction: The key stage of the EFTR procedure is the successful closure of the gastric wall defect left after full-thickness resection and thereby avoid surgical intervention. This report presents a new method of closing large gastric defects left after EFTR, using LeClamp™ endoloops and metallic clips by means of single-channel endoscope.

Aims & Methods: We retrospectively analyzed 68 patients who presented at four institutes between April 2014 and October 2014 with gastric fundus GISTs arising from the MP and who consequently underwent EFTR, with the resulting large gastric defects being closed using novel endoloops (Loop-20 and Loop-30, LeClamp™, Changzhou, China) and metallic clips (HX-600-135; Olympus). The key steps of closure were (1) An endoloop was inserted into the gastric cavity by forceps through the single-channel therapeutic endoscope; (2) The endoloop was anchored onto the full thickness of the defect’s distal margin with the clip, followed by insertion of several additional clips to anchor the endoloop at different sides of the margin; (3) The delivery system was inserted and a removable hook was connected with the endoloop; (4) The endoloop was tightened by slight pulling of all the edges together; (5) Other clips were used if any clip was not accurately positioned or the purse-string suture was not tight. Patient characteristics, tumor size, en bloc resection, and postoperative complications were evaluated.

Results: A total of 68 patients (27 men [40%], 41 women [60%]; median age 55 years, range 38–67) were successfully underwent EFTR and the en bloc resection rate was 100%. Completely closure of all the gastric full-thinkness defects was achieved (success rate 100%). The median suture operation time was 13 minutes (range 9–21min). The mean maximum size of the lesions was 2.3cm (range 1.5–3cm). Pathological examination determined that all of the lesions were GISTs. The tumors were all low risk or very low risk, with a low mitotic index. No further treatment was given. The median hospital stay after the procedure was 5.4 days (range 3–9). None of the patients experienced severe complications, such as delayed bleeding, peritonitis or abdominal abscesses. Contrast roentgenography on post-procedure day 3 showed that no patients had gastrointestinal tract leakage or disturbed gastric emptying. None of the 68 patients underwent any surgical operations for the treatment of their lesions. All the patients had follow-up visits and the wounds were healed in all cases 1 month after the procedure. No residual tumor or tumor recurrence was observed during the follow-up period (range 6–12 months).

Conclusion: The use of LeClamp™ endoloops and metallic clips is a relatively safe, easy, and feasible method for repairing gastric defects resulting from EFTR.

Disclosure of Interest: None declared

P0751 ESD TRAINING IN CHINA: EXPERIENCE FROM HYBRID KNIFE HANDS-ON WORKSHOPS IN ZHONGSHAN HOSPITAL

Y. Zhong¹, J. Li¹, L. Yao¹

¹Zhongshan Hospital of Fudan University, Endoscopy Center, Shang hai, China

Contact E-mail Address: lijian15952870985@163.com

Introduction: Endoscopic submucosal dissection (ESD) is the gold standard technique for en bloc resection of superficial tumors of the gastrointestinal tract [1]. Hands-on endoscopy workshops are popular and valuable source for training of ESD. In China, ESD experience remains limited. Endoscopy Center, Zhongshan Hospital was the first endoscopy center to provide ESD in China back in 2006 [2], and has been a destination for ESD training since 2009.

Aims & Methods: The aim of the study is to evaluate the efficacy and safety of short-term hands-on workshops in ESD and to assess the progress of ESD practice in China following endoscopic training at the Zhongshan Hospital, with special attention to both short-term outcomes during the course and to the later ESD experience of the trainee’s hospitals, in order to help setting the standards for adequate training and certification for ESD. From 2009 to 2013, ESD hands-on workshops have been held at Zhongshan Hospital. The workshops included lectures, ESD live demonstrations and hands-on training on live porcine models. Follow up questionnaires were sent to all 550 trainees at 464 hospitals in October 2014, with 460 trainees responding.

Results: There were 550 doctors who were trained during the 23rd hands-on workshops held Zhongshan Hospital, the median number of course trainees was 25 (ranging between 7-32). Completed questionnaires were returned by 460 (83.6%) trainees. There were 417 trainees who started performing ESD after the course. 28 doctors attended the workshop twice, and performed better than trainees who attended once in the hands-on practical session. Performance in the practical session has a significant difference both in the trainees GI experience (> 5years vs≤ 5years) and GI endoscopies (>4000 vs ≤ 4000). Following up the trainees within 1-year, there were 378 (82.2%) respondents from high-volume medical centers, with one-third of the respondents had experience in ESD.

Conclusion: Hands-on endoscopy workshops are useful in introducing ESD for trainees. Results showed that our training model is safe and enable novice endoscopists to start performing ESD. Requirements for starting ESD training include prior GI endoscopy experience, intensive learning and simulated ESD on live animal models under instructor’s supervision. Essential requirements for trainees starting ESD remain to be established, but our system provides a step on the way.

Disclosure of Interest: None declared

P0752  ENDOSCOPY IN VARICEAL BLEEDING: OPTIMAL TIME TO RESCOPING

L. Nunn¹, C. Shekhar², R. Mohammad³, N. Fisher³, S. Ishaq³

¹Medical School, University of Birmingham, Birmingham, ²Gastroenterology, Manor Hospital, Walsall, ³Gastroenterology, Russells Hall Hospital, Dudley, United Kingdom

Contact E-mail Address: drcshekhar@gmail.com

Introduction: Variceal haemorrhage is a common and potentially lethal complication of cirrhosis (1). Variceal rebleeding can occur in 20% of cases in the first week following the acute episode (2). BSG guidelines published in 2000 suggested endoscopy at weekly interval, whereas the AASLD guideline from 2007 suggest at 1-2 week interval and most recent ASGE guideline suggests optimal rescoping intervals of 1-8 weeks, a wide-ranging time scale recommendation classified as low-grade evidence (3,4,5). There is also primary literature that indicates that rescoping in less than 3 weeks might increase risk of harm (6).

Aims & Methods: We reviewed our practice to assess compliance with guidelines.

Method: We carried out a retrospective review of endoscopic procedures and follow up after oesophageal variceal bleeds at a DGH in the West Midlands over a 12-month period from August 2012 onwards. We recorded the date of their first variceal bleed (index bleed) and the scheduled follow up endoscopy procedure. We also recorded any adverse events such as rebleeds (bleeds in <7 days since the index bleed) or interval bleeds (bleeds that occurred >7 days post index bleed).

Results: 31 patients identified during 12month period had total 45 acute variceal bleeds, requiring urgent endoscopy. Haemostasis was achieved in all but one occasion 97.8% (44/45), with the majority (32) receiving band ligation and remaining receiving sclerotherapy or combination of therapies. 20% of total bleeds had rebleeds or died within 7 days. Of the remaining 36 bleeds, 14% had scheduled repeat endoscopy in <7 days as per last BSG guidelines, 29% had scheduled endoscopy between 1-8 weeks, which conforms to the standards suggested in new ASGE guideline, 20% had follow up endoscopy after 8 weeks, and 37% had no follow up endoscopy. The mortality rates of the people rescoped within 0-2 weeks and 2-8 weeks were 78% and 23% respectively with multiple reasons contributing.

Conclusion: There is inconsistency in the duration to follow up endoscopy practice perhaps due to wide discrepancy in available guidance and patient compliance. It is likely that in real-life practice in UK, rescoping interval is variable and inconsistent. It would be helpful to reassess current BSG guidelines and consider follow up endoscopy within 3-8 weeks after an index variceal bleed, with ongoing prospective review and audit to inform future adjustment.

Disclosure of Interest: None declared

P0753 ENDOSCOPIC SUBMUCOSAL DISSECTION FOR GASTRIC SUPERFICIAL NEOPLASTIC LESIONS: A EUROPEAN II LEVEL CENTER EXPERIENCE

L. Petruzziello¹, M. Campanale¹, G. Andrisani¹, G. Gullo¹, S. Greco¹, C. Spada¹, G. Costamagna¹

¹Endoscopy Unit, Catholic University of Rome, Rome, Italy

Contact E-mail Address: chiaracampanale@hotmail.com

Introduction: Endoscopic dissection for the treatment of gastric superficial neoplastic lesions is an established first-line treatment in Eastern countries, its role has yet to be considered in Western guidelines, mostly due to a lack of long-term studies. The aim of this study was to describe the efficacy, safety and long-term outcomes for endoscopic submucosal dissection (ESD) in the treatment of gastric lesions in our center.

Aims & Methods: This was a single-center, retrospective, cohort study between November 2007 and November 2014. A total of 60 consecutive patients with 61 gastric superficial lesions underwent ESD and were followed up for a median of 27 months.

Results: In total 60 ESD were performed. 44 (73.3) lesions matched Extended Criteria, 16 (26.7%) Guideline Criteria (standard criteria). “En bloc“ resection was feasible in 95%, with R0 resection rates of 86.6% (Ext-G 38/44 86.4% vs St-G 14/16 87.5% p:n.s). In total, 60 gastric lesions were classified as 33 (55%) adenocarcinomas intestinal type according to Lauren classification, 2 (3.3%) adenocarcinomas diffuse type according to Lauren classification, 7 (11.67%) adenomas with low-grade dysplasia (LGD), 10 (16.67%) high-grade dysplasia (HGD), 3 (5%) ectopic pancreas, 2 (3.3%) hyperplastic lesions, 3 (5%) neuroendocrine tumors. Mean lesion size was 25.5 mm with a difference between two groups (Ext-G 28.77 vs St-G 16.50 mm, p < 0.001). 78.3% of lesions were located in third lower of stomach. Type 0-IIa + IIc according to Paris classification was the most frequent lesion in Extended group (54.5%). The recurrence rate was  18.18% (10/55 lesions of Ext-G, p:ns) at follow up of 27 months. We observed only 1 (1.6%) serious adverse events, a perforation treated with surgical resection. 9/10 complications were treated endoscopically without sequels. Surgery was performed in 7 cases (11.67 %) : 5/7 after non curative endoscopic resection and 1/7 after histological evaluation (adenocarcinomas diffuse type according to Lauren classification), 1/7 due to complications.

Conclusion: ESD is a highly effective treatment for gastric superficial lesions, without compromising cancer survival. Endoscopic resection should also be considered as first-line treatment for gastric neoplasias in Western countries.

Disclosure of Interest: None declared

P0754 HEMOSPRAY AS A “RESCUE” ENDOSCOPIC TREATMENT IN GASTROINTESTINAL BLEEDING: A BINATIONAL OBSERVATIONAL STUDY

M. Karin¹, H. Ivekovic², B. Bilic², N. Rustemovic², S. Glavas³, K. Nahodovic³, V. Papovic³, N. Vanis³, R. Mesihović³

¹Gastroenterology, Clinical hospital, Mostar, Bosnia and Herzegovina, ²Gastroenterology and Hepatology, University Hospital Centre, Zagreb, Croatia, ³Institute of Gastroenterohepatology, Clinical Center Sarajevo, Sarajevo, Bosnia and Herzegovina

Contact E-mail Address: majagr@net.hr

Introduction: Hemospray is a novel hemostatic agent for the management of gastrointestinal bleeding (GIB). Herein we describe the experience with Hemospray in our cohort of patients with GIB.

Aims & Methods: This was a binational multicentre observational study done at three tertiary hospitals in Croatia and Bosnia and Herzegovina. Consecutive patients with GIB refractory to standard endoscopic hemostasis were included in the study. The patients referred for surgery, or in whom the informed consent for endoscopy was not obtained, were excluded from the study.

Results: There were 16 patients (median age 66.5 yrs, range 47-91, 11 males) with active GIB in whom Hemospray was applied. Lesions in the upper GI tract included: peptic ulcer bleeding (n=4), Cameron lesion (1), Mallory-Weiss (1), GAVE (1), esophageal cancer (3). Lesions in the lower GI tract included: post-polypectomy bleeding (n=5), bleeding polyp (1) Severity of bleeding was classified as spurting in 5 pts, oozing (7), visible vessel (1) and can’t tell (3). A total of 6 patients were receiving anticoagulant or/and antithrombotic therapy. Bleeding with spurting vessel was in 31.25% of patients, in the form of oozing in 43.75%, and 25% of patients had visible blood vessel. Previous endoscopic treatment was recorded in 10 pts (clips=7, nylon snare=1, injection therapy=1). Rebleeding at 7 days was noted in one patient (6%) with the post-polypectomy bleeding, who was referred to surgery. During the follow-up period (median 3 months, range 1-6), no re-bleeding episodes were recorded and two GIB-unrelated deaths occurred (12.5%). During study period we did not observe any side-effects of Hemospray.

Conclusion: In our cohorts of patients the use of Hemospray was efective treatment option for patients with GIB.

Disclosure of Interest: None declared

P0755 THE DEVELOPMENT OF A NOVEL DEVICE FOR TRANSPLANTATION OF CELL SHEETS IN THE FIELD OF THE PHARYNX

M. Abe¹, M. Maeda², N. Kanai², K. Hori¹, Y. Kawahara¹, H. Okada¹, M. Yamato²

¹Gastroenterology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, ²Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University (TWIns), Tokyo, Japan

Contact E-mail Address: makotabe7@gmail.com

Introduction: With the development of image-enhanced endoscopy and endoscopic diagnosis, the number of superficial cancer in the oropharynx and hypopharynx is increasing. The endoscopic submucosal dissection (ESD), endoscopic mucosal resection, or endoscopic laryngopharyngeal surgery is performed for these superficial squamous cell carcinomas. Because of complicated structure of pharynx, when ESD was performed for the lesion near the pyriform sinus, postoperative adhesion was observed. It impairs swallowing function and becomes the cause of aspiration pneumonitis. And similar to the esophageal ESD, postoperative stricture is observed when a large area of mucosa was removed. Some study showed the endoscopic transplantation of fabricated autologous epithelial cell sheets prevent postoperative stricture. It is expected same effect after the ESD of the oropharynx and hypopharynx. However, because of the narrow and complicated 3-dimensional structure of pharynx, we can transplant the cell sheets on only a limited area by using existing transplant method and devices. So, it was impossible to investigate an effect of the cell sheet transplantation in the field of the pharynx.

Aims & Methods: To transplant cell sheets to entire field of the oropharynx and hypopharynx after ESD, The novel devices were designed and developed with a computer-aided design system, and the three-dimensional data were transferred to a 3-D printer. And then, primary epidermal cells were isolated from the lower abdominal skin of miniature pigs, cultured for 14 days at 37°C on temperature-responsive culture inserts. Transplantable cell sheets were harvested from the inserts by reducing temperature to 20°C. We performed pharyngeal ESD and cell sheets transplantation with this device in a porcine, and investigated the feasibility of these in the field of the oropharynx and hypopharynx.

Results: Developed novel endoscopic delivery device was consisted of a cell sheet carrier and an air tube. A cell sheet carrier was spoon-shaped and covered by balloon, and connected to an air tube. It could attach the cell sheets by inflating the balloon that inflated only one side. It could deliver the cell sheets without contacting the mouth and laryngopharyngeal mucosa, and deliver the cell sheets on any areas of the pharynx after circumferential ESD. Required cell sheets were successfully transplanted to cover the ulcer site.

Conclusion: The novel device was very useful. Owe to this device, now we can investigate an effect of the cell sheets transplantation after pharyngeal ESD.

Disclosure of Interest: M. Abe: None declared, M. Maeda: None declared, N. Kanai: None declared, K. Hori: None declared, Y. Kawahara: None declared, H. Okada: None declared, M. Yamato Shareholder: Share holder of CellSeed Inc., Tokyo, Japan

P0756 SUCCESFUL TREATMENT OF ACHALASIA BY POEM IN ROMANIA: A REPORT ON THE FIRST 30 CASES

M. Tantau¹, A. Tantau², C. Tefas¹, C. Buzas¹, A. Hadade¹, G. Mester¹

¹Gastroenterologie, Institutul Regional de Gastroenterologie i Hepatologie Prof. Dr. Octavian Fodor, ²Spitalul Universitar CF, Cluj Napoca, Romania

Contact E-mail Address: tefascristian@gmail.com

Introduction: Peroral endoscopic myotomy (POEM) is now the proposed method to replace laparoscopic mytomy in the treatment of achalasia, being less aggressive, with lower morbidity and similar or even higher efficiency. Thus, POEM is reserved for expert endoscopists.

Aims & Methods: The main purpose was to analyze the efficacy and complications of the technique, while the secondary purpose was to evaluate the clinical, endoscopic and manometric improvement in patients after treatment. Endoscopic, radiological and manometric assessments were performed in all patients before and after the procedure. All POEMs were performed by a highly experienced endoscopist with no previous hands-on training. We evaluated the resolution of symptoms at 3 and 30 days after POEM using the Eckardt score. The technique, accessories and electrocautery settings used were those described by Prof. Inoue (1). An esophagography was performed in all patients after the procedure to rule out any leakage. All patients were allowed to eat 48 hours after POEM.

Results: From November 2013 to April 2015, thirty patients were treated by POEM, with a mean age of 43.7 years. Five patients had previous endoscopic balloon dilation. No patient had previous surgical myotomy. The average duration of the intervention was 87.5 minutes. We recorded five incidents, three in the form of esophageal and gastric mucosal microperforations, closed safely with endoscopic clips, one subcutaneous emphysema, for which temporary cessation of the intervention was necessary, and one pneumoperitoneum, for which transumbilical decompression using a Veress needle was necessary. We also recorded two complications in the form of postprocedural endoscopic clip slippage, which required endoscopic reintervention. We noted a decrease in Eckardt score from a mean 7,7 before POEM to a mean 0,8, 30 days after POEM. We also recorded a decrease in LES pressure from a mean 35,5 mmHg before the procedure to 3 mmHg, 30 days after the procedure.

Conclusion: POEM is an effective and safe technique. An experienced gastroenterologist can perform it without the need for hands-on training in advance, due to a reduced learning curve.

Disclosure of Interest: None declared

P0757 OUTCOMES OF ENDOSCOPIC INJECTION OF MITOMYCIN C FOR REFRACTORY RECURRENT BENIGN ESOPHAGEAL STRICTURES

M. I. Canto^1,2,*, K. Lynch¹, M. Khashab¹, E. J. Shin¹, P. Okolo¹, A. Kalloo¹

¹Medicine (Gastroenterology), ²Oncology, Johns Hopkins Medical Institutions, Baltimore, United States

Contact E-mail Address: mcanto@jhmi.edu

Introduction: Benign esophageal strictures are a common problem characterized by luminal narrowing due to acid exposure, radiation, caustic injury, or post-surgical changes. The production of collagen and fibrous tissue stimulated by esophageal injury results in chronic stenosis. Up to 35% of benign strictures recur are recalcitrant. Mitomycin C is a chemotherapeutic agent that inhibits both DNA and protein synthesis following intracellular enzymatic reduction resulting in slowing of cell division and fibroblast proliferation ¹. Topical MMC has been used in children and adults to treat laryngeal and tracheal strictures ^2,3. Limited data of MMC topical mucosal therapy in children and adults suggests promising safety and efficacy for recalcitrant esophageal strictures ⁴.

Aims & Methods: We report the clinical outcomes of 9 patients with refractory benign esophageal strictures treated with endoscopic submucosal injection of MMC(0.4 mg/,l) after dilation⁴.

Results: 9 symptomatic patients with 11 refractory esophageal strictures previously treated with numerous dilations (median 4), steroid injections and/or stents underwent MMC treatment. A total of 16 intralesional endoscopic injections were made. 3 patients with complex strictures required more than 1 MMC treatment. Pre-MMC mean stricture length and diameter were 3.7cm (range 1-10cm) and 5.5mm (range 2-10mm), respectively. Mean patient follow-up time was 14 months (range 6.3-49.8 months). Symptomatic recurrence requiring unscheduled intervening therapy was observed in 4/9 patients within the first 3 months (2 dilation, 1 stent, 1 dilation + MMC). Partial response (post-MMC dysphagia score improved by at least 1 grade) was noted in all. A durable complete response was defined as no dysphagia and no intervening therapies at last follow-up. This was observed in all except 1 patient who required stenting within 6 months. MMC injection decreased pre-treatment intervention therapy from median 3.8 procedures per 6 months (interquartile range 3 to 4.5 per 6 months) to 0 procedures in 6 months (p=0.008,Wilcoxon signed rank). There were no treatment-related adverse events with endoscopic injection of a total of 0.64 to 6.4 mg MMC per patient.

Conclusion: MMC injection for refractory recurrent benign esophageal strictures is safe, eliminates dysphagia, and significantly decreases symptom recurrence and the need for subsequent interventions.

Disclosure of Interest: None declared

P0758 NITROUS OXIDE CRYOTHERAPY FOR TREATMENT OF ESOPHAGEAL SQUAMOUS CELL NEOPLASIA (ESCN): INITIAL EXPERIENCE WITH A NOVEL PORTABLE CRYOBALLOON FOCAL ABLATION SYSTEM (CBFAS)

M. I. Canto¹, K. Lynch¹, E. J. Shin¹, J. A. Almario¹, H. Cosby¹, B. Jobe², Y. Komatsu²

¹Medicine (Gastroenterology), Johns Hopkins Medical Institutions, Baltimore, ²Surgery, Allegheny Health Network, Pittsburgh, United States

Contact E-mail Address: mcanto@jhmi.edu

Introduction: Early esophageal squamous cell neoplasia (ESCN) can be successfully treated with radiofrequency ablation (RFA), endoscopic mucosal resection (EMR), or endoscopic submucosal dissection (ESD), but strictures can develop¹. Endoscopic cryotherapy can successfully eradicate neoplastic Barrett’s esophagus^{2, 3}, including those that failed other treatments^{2, 4}. A new portable battery-powered contact cryotherapy system using nitrous oxide (cryoballoon focal ablation system, CbFAS) has been used for Barrett’s esophagus⁵ with promising early results⁶.

Aims & Methods

Aim: To determine the feasibility of endoscopic eradication of ESCN with nitrous oxide cryotherapy using a CbFAS.

Methods: Patients with ESCN who had failed or were ineligible for EMR/RFA (stricture, esophageal varices) were treated with nitrous oxide cryoballoon ablation using the CbFAS, which consists of a small hand-held device containing liquid nitrous oxide, which converts to gas within a low pressure compliant through-the-scope balloon. It freezes targeted mucosa in contact with the balloon, resulting in ablations of approximately 2 cm². After chromoendoscopy, all Lugol’s voiding lesions (LGLs) were treated with multiple focal ablations (8-10 seconds of ice per site). Post-procedure adverse events were recorded. Patients were treated every 6-8 weeks until targeted and random biopsies demonstrated eradication of neoplasia.

Results: 3 male patients (mean age 66, range 55-76) with multifocal low-grade intraepithelial neoplasia (LGIN), high grade intraepithelial neoplasia (HGIN), or flat type ESCC involving 3 cm (Pt1), 4 cm (Pt2), and 10 cm (Pt3 ) of the esophagus had 3, 8, and 10 ablations at the index procedure, respectively. Residual LGLs were treated in a second (Pt2) and third procedure (Pt3). No device malfunction was noted. Aiming the cryogen at LGLs was relatively easy. Median procedure time was 34 min (range 18-57). No major adverse events occurred. One patient had mild odynophagia and chest pain. No strictures or bleeding developed. Squamous regeneration was seen in all treated areas with no LGLs and complete pathologic response achieved in all patients with short term follow-up (mean 165 days, IQR 35-316).

Conclusion: Our initial experience suggests that multifocal cryoballoon ablation is a promising portable, technically simple, well-tolerated, safe and effective endoscopic therapy for ESCN, including extensive disease refractory to EMR and RFA. Prospective studies are needed to optimize cryogen dosimetry and assess safety and long-term efficacy.

Disclosure of Interest: M. I. Canto Financial support for research: Participated in clinical trial on BE cryoballoon ablation 2013-2014 sponsored by C2 Therapeutics. This work was not sponsored by the company., K. Lynch: None declared, E. J. Shin: None declared, J. Almario: None declared, H. Cosby: None declared, B. Jobe: None declared, Y. Komatsu: None declared

P0759 PERCUTANEOUS TRANSESOPHAGEAL GASTROTUBING (PTEG) FOR THE PATIENTS THAT PERCUTANEOUS ENDOSCOPIC GASTROSTOMY (PEG) INSERTION IS IMPOSSIBLE – USEFULNESS OF ENDOSCOPICALLY ASSISTED PROCEDURE

M. Murakami¹², K. Nishino², S. Murakami², K. Mori², B. Murakami², M. Azuma³, S. Tanabe¹, M. Kida¹, W. Koizumi¹

¹Internal Medicine, Kitasato University School of Medicine, Sagamihara, ²Internal Medicine, Murakami Memorial Hospital, Saijo, ³Internal Medicine, Kitasato University School of Medicine, Agamhara, Japan

Contact E-mail Address: masato@murakami-kinen.or.jp

Introduction: Percutaneous transesophageal gastrotubing (PTEG) was developed as an alternative route to access the gastrointestinal tract for the patients that Percutaneous Endoscopic Gastrostomy was contraindicated with conditions such as prior gastrectomy, gastric anterior wall malignancies, or massive ascites. PTEG by endoscopic assistance may enhance the safety of the procedure.

Aims & Methods: The aim of this study is to evaluate the clinical usefulness of PTEG supported by endoscopy. A rupture-free balloon (RFB) catheter is inserted into the lower esophagus. Percutaneous balloon puncture with a specialized needle is then performed from the left side of patient’s neck under ultrasonographic control. A guide wire is inserted through the needle into the RFB, followed by a dilator and sheath. A placement tube is then inserted through the sheath, and the sheath is removed. We started to perform PTEG under endoscopy or fluoroscopy in a total of 144 patients (93 men and 51 women, mean age 72.0 years) in whom PEG was not feasible. PTEG was performed for nutrition in 82 patients and for decompression in 62.Thirty patients were started by fluoroscopic assistance and 114 patients were started by endoscopic assistance.

Results: Satisfactory results were achieved in all 144 patients. Median follow-up was 64.0 days in patients who received decompression because of the obstruction due to malignancies and 255.5 days in those who received nutrition. Seven of 82 patients for nutrition were able to free from tube feeding due to PTEG tube feeding support. There was 1 patient with severe bleeding requiring blood transfusion in the fluoroscopy group. one patient had tracheal penetration, which was managed conservatively. Other complications were minor oozing bleeding in eight patients that did not require blood transfusion, subcutaneous emphysema in two patients, which were managed conservatively. The complication rate associated with fluoroscopically and endoscopically assisted PTEG was 20.0% and 14.1%, respectively. No patient required surgical treatment or died after PTEG.

Conclusion: PTEG is feasible, safe, and useful. PTEG could be an optimal procedure for long-term nutrition and/or decompression even for the patients who failed PEG insertion. The use of endoscopy enhances the safety of the procedure and allows better confirmation of each step involved.

Disclosure of Interest: None declared

P0760 A SELF-ASSEMBLING, MATRIX-FORMING PEPTIDE CAN BE USED TO PREVENT POST OPERATIVE BLEEDING AFTER ENDOSCOPIC RESECTION INCLUDING IN HIGH-RISK SITUATIONS

M. Pioche¹, M. Camus², J. Rivory³, S. Leblanc², I. Lienhart⁴, E. Thimonnier⁴, S. Chaussade², F. Prat², T. Ponchon⁴

¹Gastroenterology and endoscopy division, Pavillon L, Hôpital Edouard Herriot, Lyon, ²Gastroenterology and endoscopy division, Cochin hospital, Paris, ³Gastroenterology and endoscopy division, Edouard Herriot Hospital, ⁴Gastroenterology and endoscopy, Pavillon L, Edouard Herriot hospital, Lyon, France

Contact E-mail Address: mathieu.pioche@chu-lyon.fr

Introduction: Endoscopic resections can remove superficial digestive neoplasia with low morbidity and mortality. Nevertheless, delayed bleeding has been reported in approximately 1, 5, 15 and 2% after resection in the esophagus, the stomach, the duodenum and the rectum, respectively, increasing with antiplatelet/anticoagulant therapy or in case of portal hypertension. A self-assembling peptide (SAP) forming a gel in appropriate conditions of ionization could protect the mucosal defect during the early phase of healing. The aim of this clinical trial was to assess the safety and efficacy of the SAP to prevent delayed bleedings after endoscopic resections.

Aims & Methods: Consecutive patients who underwent endoscopic resections for esophageal, gastric, duodenal or colic superficial lesions were enrolled in two university hospitals. We also included patients with high risk of bleeding like patients with antiplatelet agents, anticoagulation drugs with heparin bridge therapy and cirrhosis with portal hypertension. The SAP gel (Purastat®, 3D Matrix, Ltd) was apllied immediately after resection. The volume of gel depended of the resection size and was applied with a catheter aiming to cover all the ulcer bed. Subsequent patient management included oral PPI after esophageal, gastric and duodenal resections. The primary endpoint was the rate of post resection bleeding. Ease of use and safety were also assessed.

Results: 37 patients were included with 42 lesions (8 esophagus, 10 stomach, 8 duodenum, 3 ampullary, 13 colorectal tumors). Among those 42 lesions, 28 were resected in high-risk situations (8 non-discontinued anti-platelets drugs, 6 heparin bridge therapies followed by anticoagulant drugs at day 1, 9 with cirrhosis and portal hypertension, 1 with both cirrhosis and antiplatelet therapy, 3 large duodenal lesions and 1 lesion of the anal canal surrounded by large hemorroids). The resection technique was ESD in 22 cases, en-bloc EMR in 9 and piecemeal EMR in 5. The mean lesion size was 17.1 mm (SD 18.4) with a mean area of 2.94 cm² (SD : 3.2). The mean volume of Purastat® used was 3.1 ml (SD : 1.5 ml) in a mean time of 2.0 min (SD : 1.2). No difficulty was noted during application. Four delayed overt bleedings occured (9.5 %) (3 hematochezia, 1 hematemesis) needing endoscopic hemostasis in 3 cases. The mean hemoglobin drop off was 0.8 g/dl (-0.1to 2.1 g/dl). There were no adverse events related to the gel.

Conclusion: The use of this novel EMS may help to reduce the post endoscopic resection bleedings including in high risk situations. Its use is easy and safe but further comparative studies are needed to fully evaluate its effectiveness.

Disclosure of Interest: None declared

P0761 PRELIMINARY EVALUATION OF SUBMUCOSAL TUNNELING ENDOSCOPIC RESECTION FOR THE TREATMENT OF LARGE SYMPTOMATIC SUBMUCOSAL TUMORS ORINGINATING FROM THE MUSCULARIS PROPRIA LAYER IN THE ESOPHAGUS AND CARDIA

M. Xu¹, C. Zhang¹, on behalf of Chen Zhang, Quan-Lin. Li, Mei-Dong. Xu

¹Endoscopy center, Zhongshan Hospital, Shanghai, China

Contact E-mail Address: xumeidong@aliyun.com

Introduction: Submucosal tunneling endoscopic resection (STER) has been proved to have many advantages for small upper gastrointestinal (GI) submucosal tumors (SMTs) originating from the muscularis propria (MP) layer. Here, we report the clinical value of STER for huge (≥3cm) and symptomatic SMTs originating from the MP layer in the esophagus and cardia.

Aims & Methods: Our study aimed to evaluate the clinical value of STER for large symptomatic submucosal SMTs originating from the MP layer in the esophagus and cardia. A total of 72 large symptomatic SMTs originating from the MP layer in the esophagus and cardia were treated by STER between May, 2011 and December, 2013. Large symptomatic tumors referred to the tumors which were not less than 3 cm in maximum diameter and caused varying degrees of retrosternal or epigastric discomfort, regurgitation, odynophagia, and/or dysphasia. After located, a submucosal tunnel was created to expose the tumor. The lesion was then resected under direct endoscopic view and the tunnel entry was closed with several metal clips.

Results: STER was performed successfully in all cases, and the en bloc resection rate was 100%. The median maximum diameter of the specimens was 4.0 cm. Pathological results revealed 69 leiomyomas, 1 stromal tumor, 1 schwannoma and 1 cyst. STER-related complications were listed in Table 1. All of those complications were treated successfully after conservative treatments. No patient encountered massive and delayed bleeding, intra-tunnel infection or abscess, and procedure-related death. The symptoms of retrosternal or epigastric discomfort, regurgitation, odynophagia and/or dysphasia were relieved varying degrees after the procedures according to patients’ subjective feelings. An objective relief of dysphagia was also achieved as assessed by Stooler’s dysphagia score (P < 0.001). No tumor residual or recurrence was found during the follow-up period (range, 2-30 months)

Table 1 Clinicopathologic information of the 72 patients

. Patients N=72

Age, median (range), years 46 (28-67)

Sex, n (%). Male 50 (69.4) Female 22 (30.6)

Lesion size, median (range) cm 4.0 (3.0-7.0)

Procedure time, median (range) min 70.0 (42-140)

Tumor location, n (%) . Esophagus 60 (83.3) Cardia 12 (16.7)

Chief complaint, n (%) . Retrosternal or epigastric discomfort 72 (100.0) Regurgitation 56 (77.8) Odynophagia 60(83.3) Dysphasia 72 (100.0)

EUS layer, n (%) . Superficial MP 31 (43.1) Deep MP 41 (56.9)

Pathologic diagnosis, n (%) . Leiomyoma 69 (95.8) GIST 1 (1.4) Schwannoma 1 (1.4) Cyst 1 (1.4)

Complications, n (%) .Substernal or epigastric pain Analgesics required Mucosal damage Closures required 41 (56.9) 3 (4.2) 4 (5.6) 4 (5.6)Pneumothorax Subcutaneous emphysema Diaphragmatic emphysema Pneumoperitoneum Pleural effusion Massive and delayed bleeding Intra-tunnel infection or abscess Surgical-related death Tumor residual or recurrence 9 (12.5) 18 (25.0) 19 (26.4) 9 (12.5) 34 (47.2) 0 (0) 0 (0) 0 (0) 0 (0)

Conclusion: STER is safe and effective for large symptomatic SMTs originating from the MP layer in the esophagus and cardia. The procedure can significantly relieve symptoms without severe adverse events. High en bloc resection rate and accurate histopathologic outcomes can also be achieved with the technique.

Disclosure of Interest: None declared

P0762 ANALYSIS OF CLINICOPATHLOGIC FACTORS THAT AFFECT ON PROCEDURE TIME OF ENDOSCOPIC SUBMUCOSAL DISSECTION

M. W. Jung¹, S. J. Shin¹, K. M. Lee¹, S. G. Lim¹

¹Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea

Contact E-mail Address: jmw_81@hanmail.net

Introduction: Endoscopic submucosal dissection (ESD) has become a widely accepted therapeutic method for gastric adenoma and early gastric cancer. However, it takes a long time to perform ESD procedure because of technical difficulties. So there has been a lot of effort to analyze factors that have an affect on procedure time. Especially, in this study, we analyzed not only total procedure time but also subdivision of the time -inspection, incision, dissection, coagulation time.

Aims & Methods: We reviewed the data of 343 patients who underwent ESD for 378 lesions (gastric adenoma and early gastric cancer) from July 2006 to December 2012 by one skillful endoscopist. Clinical outcomes of ESD such as procedure time, location, pathology, size, invasion depth were analyzed.

Results:

Abstract number: P0762 Table 1.

Mean ESD time of cases with pathology and invasion depth

		InspectionTime(min)	IncisionTime (min)	DissectionTime (min)	CoagulationTime (min)	TotalTime (min)
Pathology	Adenoma	3.54	15.97	30.12	6.98	56.36
	Adenocarcinoma	3.81	19.41	47.44	8.08	79.09
	P value	0.051	0.013	0.001	0.566	0.001
Invasion depth	M	3.62	17.93	36.68	7.04	65.09
	MM	3.58	18.38	37.46	6.32	66.00
	SM	4.71	19.75	77.92	6.08	110.33
	P value	0.383	0.767	0.001	0.659	0.001

Mean total procedure time was 64.9 min, and mean inspection, incision, dissection, coagulation time were 3.68, 17.27, 36.65, 7.32 min respectively. Univariate analysis showed the total ESD time was closely related to pathology (p=0.001), tumor invasion depth (p=0.001), location (p=0.002), size (p=0.001), ulceration (p=0.001) and depression (p=0.001). Especially, the pathology, location, tumor size, ulceration and depression were related to incision time and dissection time. Invasion depth was associated with dissection time (p=0.001). When tumor size was controlled, incision time was positively correlated with dissection time (p=0.001).

Conclusion: ESD procedure takes longer when the neoplasm is adenocarcinoma compared to adenoma. Deeper invasion depth, larger tumor size, presence of ulceration or depression are predictors of a long ESD time, especially SM invasion is related with longer dissection time.

Disclosure of Interest: None declared

P0763 ANALYSIS OF DISCREPANCIES IN HISTOLOGIC DIAGNOSES OF GASTRIC NEOPLASM BETWEEN BIOPSY AND ENDOSCOPIC SUBMUCOSAL DISSECTION

M. W. Jung¹, S. G. Lim¹, K. M. Lee¹, S. J. Shin¹

¹Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea

Contact E-mail Address: jmw_81@hanmail.net

Introduction: Endoscopic submucosal dissection (ESD) has become a widely accepted therapeutic method for gastric adenoma and early gastric cancer. A preoperative histologic diagnosis of neoplasia is a requirement for ESD. But, histologic discrepancies between endoscopic forcep biopsy (EFB) and ESD specimens have been reported at rates ranging from 2.7–49%.

Aims & Methods: Aim of this study was to analyze the prevalence of paradoxical (upgrade and downgrade) and concordant pathology results on ESD specimens and to compare their endoscopic characteristics among the each groups. Between February 2005 and December 2011, 1186 ESDs were done at Ajou University Hospital in Suwon, South Korea. Among these cases, 837 cases was diagnosed as adenoma in endoscopic forceps biopsy. We retrospectively reviewed these cases from our original database of gastrointestinal therapeutic procedures. The following variables were analyzed to document endoscopic characteristics such as size of lesion, sampling ratio and coexistence lesions.

Results:

Abstract number: P0763.

Pre-ESD biopsy result (No.)		Post-ESD result	No. (%)	Discrepancy group
Gastric adenoma (837)	Low grade dysplasia (688, 82.2%)	Non neoplasia	51 (7.4)	Downgrade
		Low grade dysplasia	511 (74.2)	Concordance
		High grade dysplasia	43 (6.3)	Upgrade
			Adenocarcinoma	83 (12.1)
	High grade dysplasia (149, 17.8%)	Non neoplasia	3 (2)	Downgrade
	Low grade dysplasia	28 (18.8)
	High grade dysplasia	36 (24.2)	Concordance
	Adenocarcinoma	82 (55)	Upgrade

Compared with upgrade and concordance group, the downgrade group showed a meaningful smaller tumor size, surface area, and lower sampling ratios (P<0.001). On the other hand, compared with concordance group, the upgrade group showed a significant larger tumor size and more frequent prevalence of ulcerative lesion (14.3%, concordance;4.0%) and depressed lesion (48.8%, concordance; 32.2%) (P< 0.001).

Conclusion: The tumor size and sampling ratio can be predictable value of downgrade group of histologic discrepancy after ESD. And the coexistant endoscopic finding such as ulcerative lesion or depressed lesion could be predictable value of upgrade group of histologic discrepancy after ESD.

Disclosure of Interest: None declared

P0764 HEMOSPRAY IN ACUTE NON-VARICEAL UPPER GASTROINTESTINAL BLEEDING: FIRST EXPERIENCES IN A UK TEACHING HOSPITAL

M. S. Hanna¹, P. Wurm¹

¹Department of Gastroenterology, Leicester Royal Infirmary, Leicester, United Kingdom

Contact E-mail Address: mina.hanna@nhs.net

Introduction: Acute Upper GI Bleeding (AUGB) is a common and serious medical emergency with an incidence ranging from 50 to 190/10 000/year in the UK.¹ Hemospray (TC-325), a hemostatic powder licensed for the treatment of non-variceal upper GI bleeding, was launched in the United Kingdom in June 2013. We introduced Hemospray into our practice at University Hospitals of Leicester [UHL] in December 2013.

Aims & Methods: The aim of our study was to assess the use of hemospray and its impact on our practice at UHL. We retrospectively reviewed our endoscopy reporting database [Unisoft- GI reporting tool] for all patients who underwent Upper GI endoscopy for AUGB [indications: melaena and/or haematemesis] and were treated with Hemospray between December 2013 and March 2015. Data was analysed for patient age, gender, endoscopic diagnosis, Monotherapy vs. combination therapy, concomitant anti-thrombotic agent use, rebleeding rate and 30 day mortality.

Results: From December 2013 until March 2015, 1299 Upper GI endoscopies were performed at UHL for AUGB. Hemostatic interventions were performed in 233 procedures [17.9%]. 19 patients were treated with Hemospray (14 male) in 21 procedures. In 19 endoscopies (90.5%) Hemospray was used at index endoscopy, while it was used at two (9.5%) second look endoscopies for rebleeding. The average age was 72 years (Range 34-94). The cause of AUGB was peptic ulceration in 78% of patients (n=14) {duodenal ulcer 78.6% (n=11) ; gastric ulcer 21.4%( n=3)}, 10.5 % oesophageal ulceration (n=2), 10.5 % gastric malignancy (n=2), 5.3% post-sphincteromy bleeding (n=1). The main reasons for Hemospray use by procedure (n=21) were: 66.7% difficult endoscopic access (n=14), 23.8 % difficulty in visualising exact bleeding point (n=5), 9.5% patient intolerance of procedure (n=2). Amongst peptic ulcers (n=14), the Forrest classification breakdown was: 1A (4, 28.6%), 1B (8, 57.1 %), 2A (2, 14.3%). Immediate hemostasis was achieved in 18/21 endoscopies (85.7 %). 9/19 patients (47.4%) were on anti-thrombotic therapy (aspirin 66.6% (n=6), clopidogrel 22.2% (n=2) and therapeutic enoxaparin 11.1% (n=1). Hemospray was used as monotherapy in 5 (23.8%) endoscopies and in combination with traditional modalities (adrenaline injection, heater probe, haemostatic clips) in 16 (76.1%) endoscopies. 5/19 patients developed rebleeding (26.4%). The average time to rebleeding was 5.8 days (Range 2-14 days). The 30 day mortality was 31.3% (n=6). 3 deaths (50%) were directly related to uncontrolled gastrointestinal haemorrhage. No adverse events as the result of Hemospray use were noted.

Conclusion: Hemospray is a safe and useful adjunct to traditional hemostatic therapies with a high rate of immediate hemostasis. In our series, Hemospray accounted for about 8% of all endoscopic interventions and was only employed in 1.5% of all patients presenting with AUGB. There was a significant rebleed rate of 26%, likely to be a reflection of a very sick patient cohort. The majority of cases had high rebleeding risk (Forrest 1A and 1B ulcers, GI malignancy). The average time to rebleed was 6 days, which suggests that Hemospray is a useful bridging therapy to non-endoscopic GI bleed therapy (angiography/surgery). A formal RCT comparing Hemospray to conventional haemostatic methods is indicated to evaluate its efficacy and effect on mortality.

Disclosure of Interest: None declared

P0765 REFRACTORY GASTROPARESIS CAN BE SUCCESSFULLY MANAGED WITH ENDOSCOPIC TRANSPYLORIC STENT PLACEMENT AND FIXATION

M. Khashab¹, S. Besharati¹, S. Ngamruengphong¹, V. Kumbhari¹, M. H. El Zein¹, A. Abdelgelil¹, A. H. Tieu¹, G. E. Mullin¹, E. M. Stein¹, S. Dhalla¹, M. Nandwani¹, V. Singh¹, M. Canto¹, A. N. Kalloo¹, J. Clarke¹

¹Gastroenterology, Johns Hopkins University, Baltimore, United States

Contact E-mail Address: mkhasha1@jhmi.edu

Introduction: Medical treatment options for gastroparesis are limited. Data from studies of botulinum toxin and pyloroplasty suggest that disruption of the pylorus can result in symptomatic improvement in some patients with refractory gastroparetic symptoms. We previously performed a pilot study that demonstrated improvement of symptoms in 4 patients with gastroparesis treated with transpyloric stent placement (TPS).

Aims & Methods: To (1) determine safety and efficacy of TPS placement for refractory gastroparesis; and (2) evaluate whether various stent fixation techniques had impact on stent migration rate and clinical outcome. Patients with gastroparesis refractory to medical treatment were referred for TPS. A through-the-scope fully covered self-expandable metallic esophageal stent was deployed across the pylorus. In fixation group, the stent was anchored to the gastric wall with either endoclips, over-the-scope clip (OTSC) or endoscopic suture (ES: placed in 2 locations between stent and gastric wall). Self-reported symptom improvement, stent migration rate and post-stent gastric emptying study (GES) results were collected. Time to migration was compared using Kaplan Meier estimate.

Results: A total of 29 patients (20 female, mean age 39yr) with refractory gastroparesis (idiopathic 16, diabetic 8, post-surgical 5) underwent 47 TPS procedures. Of these, 25/47 (53%) were performed in patients admitted to the hospital with intractable symptoms. Most (n=24, 83%) had predominant symptoms of nausea (N) and vomiting (V). Successful stent placement was achieved during 46 (98%) procedures. Most stents were anchored to the gastric wall using ES (n=23), followed by OTSC (n=18) and endoclip (n=2). Three patients did not receive stent fixation. Overall, 20/27 (74%) patients had clinical response (2 patients were lost to follow-up). All inpatients were successfully discharged after stent placement. Clinical success was higher in patients with predominant N/V compared with those with abdominal pain/bloating (95% vs. 71%, p=0.12) (table 1). Repeat GES was performed in 16 patients: mean 4hr GE normalized in 5 patients (76% vs. 98%, p=0.2) and significantly improved in 4 (54% vs. 73%, p=0.02). Stent migration occurred in 59% of procedures: 100% in the no fixation group, 50% in the endoclip group, 71% in the OTSC group, and 48% in the ES group (p > 0.05 for all comparisons). During a mean follow up of 146d, time to stent migration was not different between ES and other groups (P=0.9).

Abstract number: P0765 Table 1:

Predictors of clinical response after transpyloric stent placement

	Clinical Response (n=20)	No Clinical Response (n=7)	OR	P value	CI 95%
Age(yrs)( mean ± SD)	40.95 ± 16.36	40.28 ± 14.18	1.00	0.92	0.94-1.06
Female, n(%)	14(70)	5(71)	0.93	0.94	0.13-6.22
Etiology, idiopathic, n(%)	10(50)	4(57.14)	0.75	0.7	0.13-4.2
Predominant N/V, n(%)	19(95)	5(71)	7.6	0.12	0.56-101

Conclusion: TPS is a promising novel endoscopic treatment modality for gastroparesis and improves both symptoms and gastric emptying in patients refractory to medical treatment, especially those with N/V. TPS can be considered as salvage therapy for inpatients with intractable symptoms. Questions regarding long-term durability and stent migration risk remain.

Disclosure of Interest: None declared

P0766 ACCELERATED TRAINING IN UPPER GI ENDOSCOPY - AN ANALYSIS OF SPRINT PROGRAMME OUTCOMES

N. Hawkes¹, J. Turner², J. Hurley¹, P. Neville¹, C. Geoff³, N. Warren⁴

¹Gastroenterology, Cwm Taf University Health Board, Llantrisant, ²Gastroenterology, ³Surgery, Cardiff and Vale University Health Board, ⁴WIMAT, Cardiff University, Cardiff, United Kingdom

Contact E-mail Address: Neil.Hawkes@wales.nhs.uk

Introduction: In the UK novice endoscopists must attain JAG certification in UGI endoscopy (portfolio >UGI 200 cases, trainer DOPS, achievement of performance indicators and JAG basic skills course attendance). Cases are recorded on the JETS e-portfolio (1). Barriers include need for dual accreditation in general medicine, service pressure, difficulty accessing courses and variable quality of hands-on training. In Wales we designed an accelerated national training pathway - SPRINT programme –delivering core elements with integrated simulator and lesion recognition training.

Aims & Methods: Efficiency of SPRINT training was determined by time to achieve numerical milestones, compared to previous cohorts of Welsh trainees using procedure logs from the JETS e-portfolio. SPRINT trainees evaluated each component of SPRINT training (Simulator, Lesion Recognition, endoscopic non-technical skills [ENTS]) plus an overall rating using a Likert Scale (0=no help to 10=extremely useful). Seven novice trainees were selected by GI and GI surgery training programme directors. The training programme was commenced in Sept 2014 and comprised structured induction and simulator training, JAG Basic UGI course and regional ‘Endoscopy school’ days. Data from a historical cohort of 14 trainees was used for comparison. Differences between groups were measured using a one-sided t-test (p < 0.05 significance level).

Results: Median time to each landmark was significantly faster at all stages in the SPRINT group – shifting learning curves to the left (Table) with a reduced range in completion times in the SPRINT cohort. Mean Likert scores were Simulation 7.8; Lesion Recognition 9.2; ENTS 8.8; Overall program 9.4. Trainee evaluation highlighted the main benefits as peer learning and support, faculty discussion, feedback and access to training opportunities.

Abstract number: P0766 Table: Median (IQR) for time to training landmarks (weeks) by group

No.of UGI cases	50	75	100	125	150	175	200
SPRINT GROUP	10 (7.5 to 13.5)	14 (11 to 25.5)	20 (14.5 to 29.5)	23 (20.5 to 31.5)	27 (25 to 35)	29 (29 to 37.5)	35 (33.5 to 40.5)
HISTORIC CONTROLS	22.5 (15.3 to 29.3)	35 (20 to 40.5)	45 (26.5 to 48)	51.5 (29.5 to 57.3)	58 (32.5 to 63.8)	63 (39.8 to 70)	67.5 (45.8 to 78.8)
p value for difference	0.002	0.005	0.002	0.001	0.001	0.0007	0.0008

Conclusion: A well-structured training pathway, incorporating evidence-based training methods can enhance training quality and experience for trainees and improve efficiency of training – in this case halving training time in UGI endoscopy compared to historic controls. All elements were valued by trainees. Regular contact with regional trainers acts to standardise training, improves discussion and feedback, allowing early identification and targeted support where progress is slower than expected.

Disclosure of Interest: None declared

P0767 THE DIFFERENCES BETWEEN MAGNIFYING ENDOSCOPIC IMAGING OF EARLY GASTRIC CANCER WITH BLI AND NBI WERE CAUSED BY THE PATHOLOGICAL FINDINGS AS THE DEPTHS OF CRYPTS

N. Yagi¹, R. Kimura², Y. Nakahata¹, H. Kitae¹, A. Tomie¹, Y. Oshima¹, A. Obora¹, T. Kojima¹, O. Dohi³, K. Kamada³, Y. Naito³, Y. Fujita⁴, M. Kishimoto⁴, A. Yanagisawa⁴

¹Gastroenterology, Murakami Memorial Hospital, Asahi University, gifu, ²Medical Oncology, Fukushima Medical University, Fukushima, ³Gastroenterology and Hepatology, ⁴Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan

Contact E-mail Address: nyagi@koto.kpu-m.ac.jp

Introduction: We formerly presented about the efficacy of magnifying endoscopy with blue laser imaging (M-BLI) in the diagnosis of early gastric cancers at this meeting (UEGW 2012). BLI is a novel image-enhanced endoscopy with two different lasers. In our previous presentation, we have showed that M-BLI can detect microsurface (MS) pattern at the same level of M-NBI and additionally, 75% of lesions which were showed absent MS pattern in NBI were detected irregular MS pattern in BLI. However, we couldn't quite understand the cause of that until now.

Aims & Methods: The aim of the present study is to clarify the pathological differences among these lesions which were showed absent MS pattern in NBI and irregular MS pattern in BLI. We retrospectively analyzed 20 early gastric cancers that were examined with M-BLI and NBI at the Hospital of Kyoto Prefectural University of Medicine between September 2011 and March 2014. All gastric cancers had been treated by endoscopic submucosal dissection. The following were selected on the basis of their appearance revealed by M-BLI and NBI performed beforehand: 11 lesions showing irregular MS pattern by M-BLI but absent MS pattern by M-NBI (Group A), 4 lesions with irregular MS pattern by both methods (Group B), and 5 lesions with absent MS pattern by M-BLI and NBI (Group C). The resected specimens were observed by a stereoscopic microscope, then photographed microscopic images were compared with endoscopic images. In all cases, it had been confirmed that the histological areas examined corresponded to the parts observed by both methods very closely. We examined the characteristics of the histopathological findings of each group. Furthermore, in Group A and B, the depths of three crypts in each lesion were measured using a viewer soft according to the method by Yagi (Diagn Ther Endosc 2012).

Results: In Group A, 6 of 11 lesions show histological feature that crypts were shallow, 3 lesions had histological feature that number of the ducts opens in the surface layer were few and 2 lesions had winding crypts. In Group B, all 4 lesions had deep and straight crypts. In Group C, 3 of 5 lesions were replaced with signet ring cell carcinoma in all mucosal layer, one lesion had very short intervening part and one lesion had pseudostratified cancer cells. Average depth of crypts of 6 lesions (65 ± 20 µm) in group A was significantly shallower than it of 4 lesions (265 ± 64um) in Group B (p < 0.01). Yagi reported that the depths of crypts in areas where the white zones were indistinct or invisible and those in lesions where the white zones were distinct were 81μm and 182μm, respectively in NBI. Since MS pattern is almost synonymous with white zone, it may be also that M-BLI can visualize even shallower crypt compared with M-NBI.

Conclusion: BLI may be useful for diagnosis of an extent and a submucosal invasion of early gastric cancers by visualizing the shallower crypt compared with NBI. Further study is necessary to clarify what differences of pathological findings except depth of crypts cause the differences in MS pattern findings between with BLI and NBI.

Disclosure of Interest: None declared

P0768 THE DIAGNOSIS OF INVASION DEPTH IN SUPERFICIAL ESOPHAGEAL SQUAMOUS CELL CARCINOMA: A COMPARISON BETWEEN A MAGNIFYING NARROW-BAND IMAGING OBSERVATION AND EUS

N. Matsuura¹, N. Hanaoka¹, R. Ishihara¹, S. Yamamoto¹, T. Akasaka¹, Y. Takeuchi¹, K. Higashino¹, N. Uedo¹, H. Iishi¹

¹Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka-city, Japan

Contact E-mail Address: matuura-no@mc.pref.osaka.jp

Introduction: The diagnosis of cancer invasion depth is crucial for selecting the optimal treatment strategy for esophageal cancer. Endoscopic ultrasonography (EUS) is regarded as the standard modality for diagnosing invasion esophageal cancer depth in the West. In Japan, magnifying endoscopy has been used for diagnosis by observing the architecture of the esophageal microvasculature. This modality represents a rapid and simple diagnostic procedure without the need for any additional equipment. However, the accuracy of magnifying endoscopy has not been compared with that of EUS for the diagnosis of cancer invasion depth.

Aims & Methods: Patients with esophageal squamous cell carcinoma (SCC) suspicious for muscularis mucosa or submucosal invasion in non-magnifying white light imaging were included. All patients received white-light imaging (WLI), magnifying narrow-band imaging (NBI) observation followed by EUS. Magnifying NBI observation was performed by endoscope with magnification (GIF-Q240Z, or H260Z; Olympus, Tokyo, Japan). EUS was performed using a high-resolution probe by jelly-filled method. Before examination, several syringes (5 mL) containing sufficient amounts of jelly (K-Y Lubricating jelly, Johnson and Johnson, k. k.) were prepared. After endoscope insertion (GIF-2TQ260M; Olympus) into the target area within the esophagus, a 30 or 20-MHz miniature probe was then inserted through the left channel of the endoscope and 30 to 40 mL of echo jelly was instilled through the right channel until the esophageal lumen was filled. Cancer invasion depth was diagnosed as T1a or T1b using both modalities. The diagnostic accuracy of magnifying NBI observation was compared with that of EUS while the histologic diagnosis of resected specimen served as reference standard.

Results: From January 2011 to March 2014, 204 patients with esophageal SCC suspicious for muscularis mucosa or submucosal invasion in non-magnifying WLI were examined using the two modalities. Of the 204 patients, 108 treated with chemoradiotherapy or photodynamic therapy were excluded from analysis because histologic specimens were not obtained. Ninety-six patients with 97 lesions treated either by esophagectomy (n = 25) or endoscopic resection (n = 72) were included in the final analysis. Histologic diagnosis was T1a in 48 lesions, T1b in 47 lesions, and T2 in two lesions. 4 lesions couldn’t be diagnosed by magnifying NBI because intra-epithelial papillary capillary loop couldn’t be observed. The overall accuracy of diagnosing invasion depth was 67.7% (63/93 lesions) by magnifying NBI and 71.1% (69/97 lesions) by EUS (P =0.364). The accuracy of diagnosing invasion depth in lesions with protrusions was 63% (29/46 lesions) and 80% (40/50 lesions) by magnifying NBI and EUS, respectively (P = 0.07).

Conclusion: EUS and magnifying NBI exhibited high diagnostic accuracy in esophageal SCC. Considering its simplicity of use, magnifying NBI has the potential to be the standard modality for diagnosing invasion depth of esophageal SCC. However, the diagnostic accuracy for esophageal SCC is not sufficient only with magnifying NBI. Compared with magnifying NBI, EUS has the potential to diagnose invasion depth more accurately lesions with protrusion.

Disclosure of Interest: None declared

P0769 COLON PREPARATIONS WITH PEG 4000 AND LACTULOSE: A PROSPECTIVE RANDOMIZED DOUBLE BLINDED TRIAL

K. Brescia¹, J. C. Coelho¹

¹Endoscopy, Gastrocenter, Belo Horizonte, Brazil

Contact E-mail Address: kbrescia@ig.com.br

Introduction: Colonoscopy represents nowadays one of the best diagnostic methods for colorectal diseases and for colorectal cancer screening. Good colon preparation is essencial for a high quality diagnostic examination and for the necessary therapeutic approaches. This study aims to compare two preparations regarding efficacy: The PEG 4000 preparation, which is the gold standard in the United States, and the 10% lactulose solution. Lactulose is an osmotic laxative still without formal indication as colon preparation.

Aims & Methods: It is a prospective randomized double blinded trial with 400 patients included, submitted to elective out-patient colonoscopies in private clinic. The patients were randomized in two 200 patients groups and in each one preparation was used. The Boston Bowel Praparation Scale was used in order to measure the colon preparation quality.

Results: In only 13 patiens the preparation was considered inadequate. In PEG patients only six (3%) and in lactulose patiens seven (3.5%) were considered inadequate. There was no statistical difference between both groups regarding efficacy (P = 0.778).

Conclusion: The study concluded that lactulose solution is as effective as PEG 4000 as bowel preparation for colonoscopic exams. The lactulose solution can be indicated as an option for colon preparation for colonoscopic exams. Its restrictions and contra-indications should be respected.

Disclosure of Interest: None declared

P0770 THE EFFICACY AND SAFETY OF ENDOSCOPIC SUBMUCOSAL DISSECTION USING THE “CLIP-FLAP METHOD” FOR LARGE SUPERFICIAL COLORECTAL TUMORS

K. Yamamoto¹, S. Hayashi², T. Nishida², H. Saiki¹, M. Kato¹, Y. Tokuda¹, M. Yamamoto², M. Naito¹, T. Michida³, T. Ito¹

¹Department of Gastroenterology, Japan Community Healthcare Organization (JCHO), Osaka Hospital, ²Department of Gastroenterology, Toyonaka Municipal Hospital, Osaka, ³Third Department of Internal Medicine, Teikyo University Medical Center, Chiba, Japan

Contact E-mail Address: yamamoto-kts@umic.ac.jp

Introduction: Endoscopic submucosal dissection (ESD) is technically difficult because of poor visualization and instability in the cutting area. Although the mucosal flap formation improves visualization of the cutting area, it is difficult to achieve, especially in colorectal ESD. To facilitate the mucosal flap creation, we developed the “clip-flap method” by initially substituting an endoclip for the mucosal flap until the flap is completed (K. Yamamoto, et al., Endoscopy 2012·2015).

Aims & Methods: We retrospectively studied 200 cases, in which ESD for large superficial colorectal tumors was performed at Toyonaka Municipal Hospital between 2009 and 2013. We compared the treatment outcomes after the adoption of the clip-flap method (Clipflap-ESD: 100 cases) with those before the adoption of the clip-flap method (Conventional-ESD: 100 cases) to evaluate the efficacy and safety of the clip-flap method. The procedure of the clip-flap method is as follows. After submucosal injection, the mucosa around the lesion on the anal side was incised with an adequate margin, and then the submucosal layer was cut deeply. The edge of the exfoliated mucosa was clipped with an endoclip (EZ CLIP, HX-610-135; Olympus). The distal attachment was inserted under the endoclip as well as under the mucosal flap, and then the submucosal layer was dissected with the endoknife. A single endoclip was generally used, and the cross pattern of endoclips, created by attaching one endoclip to another endoclip, was also used according to the situations. We mainly used a short-needle electrosurgical endoknife with a water-jet function (FlushKnifeBT; Fujinon), and also used other endoknives in some cases.

Results: Median tumor diameter, resected specimen diameter, procedure time, en bloc resection rate, and perforation rate of Conventional-ESD and Clipflap-ESD were 27mm vs 30mm, 34mm vs 37mm, 97minutes vs 70minutes, 91% vs 97%, and 4% vs 1%, respectively. The procedure time of Clipflap-ESD was statistically significantly shorter than that of Conventional-ESD (P < 0.01), and the differences in other parameters were not significant. Perforation was conservatively treated by clipping in 5 of 5 cases. In all cases which the clip-flap method was used, the exfoliated mucosa was lifted by the endoclip attached to the exfoliated mucosa after the distal attachment was inserted under the endoclip, allowing for clear visualization and efficient dissection of the submucosal layer, and effective creation of the mucosal flap.

Conclusion: The clip-flap method very effectively enabled the mucosal flap creation and allowed our treatment outcomes to be greatly improved. The present study demonstrates that the clip-flap method is a simple, safe, and very effective option for colorectal ESD.

Disclosure of Interest: None declared

P0772 PREVALENCE AND ASSOCIATED FACTORS OF INTERVAL COLORECTAL CANCERS AT TAIWAN

C.-E. Tsai¹, K.-L. Wu², Y.-C. Chiu², W.-C. Tai², M.-L. Hu², C.-M. Liang²

¹Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Province of China, ²Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Province of China

Contact E-mail Address: kengliang_wu@yahoo.com.tw

Introduction: Interval colorectal cancer is an emerging issue in cancer screen and surveillance. The frequency and associated factors have not been well studied in Taiwan.

Aims & Methods: We plan to clarify the prevalence and associated factors with interval colorectal cancer. The Colorectal cancer with negative colonoscopy 6 months to 36 months before cancer diagnosis was defined as interval colorectal cancer. Patients’ characteristics, past history, colon preparation, colonoscopy finding and pathology were retrospective evaluated. 670 patients with colorectal adenocarcinoma from Jan. 2005 to Nov. 2014 and who underwent colonoscopy before the diagnosis were recruited.

Results: Colorectal cancer with negative colonoscopy 6 months to 36 months before cancer diagnosis was defined as interval colorectal cancer. Patients’ characteristics, past history, colon preparation, colonoscopy finding and pathology were retrospective evaluated. 670 patients with colorectal adenocarcinoma from Jan. 2005 to Nov. 2014 and who underwent colonoscopy before the diagnosis were recruited.

Results: 22 (3.28%) patients (65.7 ± 9.2 years old; 9 male) were diagnosed as interval colon cancer. The interval colorectal cancer were predominant located at rectum and cecum (rectum 50%, cecum 18.2%, transverse colon 13.6%, sigmoid colon 13.6%, descending colon 4.5%), presented with earlier tumor stage (stage I and stage II 86.4%, stage III and stage IV 13.6%). The associated factors of interval cancer include end-stage renal disease (HR:10.494, 95% CI: 2.131-51.681), and shorter withdraw time from cecum to hepatic flexure (interval cancer: non-interval cancer 2.00 ± 0.82:4.91 ± 3.74 min) (HR: 0.561, 95% CI:0.345-0.913). Prior polypectomy and tumor size showed a tendency to develop interval colorectal cancer.

Conclusion: The prevalence of interval colorectal cancer in present study is 3.28%. Comorbidity with end-stage renal disease and shorter withdraw time from cecum to hepatic flexure could be associated factors of interval colorectal cancer.

Disclosure of Interest: None declared

P0773 THE PROSPECTIVE STUDY OF THE RELATIONSHIP BETWEEN COLONOSCOPY AND INTESTINAL ADHESION

K. Takeda¹², S.-E. Kudo¹, K. Nakahara¹, D. Takayanagi¹, M. Misawa¹, Y. Mori¹, T. Kudo¹, K. Kodama¹², S. Mukai¹, K. Wakamura¹, T. Hayashi¹, H. Miyachi¹, E. Hidaka¹, F. Ishida¹

¹Showa University Northern Yokohama Hospital, Yokohama city, ²Kakunodate Municipal Hospital, Daisen city, Japan

Introduction: When we feel scope decreased mobility at the colonoscopy, we often think that intestinal adhesion may be the reason for difficulty. But it is doubtful whether intestinal adhesion cause difficulties for endoscopy actually. We therefore sought to verify whether the scope decreased mobility is the findings as a result of intestinal adhesion prospectively.

Aims & Methods: 53 patients were performed colonoscopy and underwent laparoscopic surgery for colorectal cancer at Showa University Northern Yokohama Hospital from April 2012 to August 2012. All colonoscopist recorded the findings about colonoscopy such as time for total colonoscopy and degree of difficulty for colonoscopy (insertion grade1,2,3). And surgeon checked the location of intestinal adhesion at the laparoscopic surgery.

Results: 34 male and 19 female were included in this study. 18 cases have the abdominal surgical history and in all cases, intestinal adhesion was observed. On the other hand, intestinal adhesion was also observed in 28 cases have no surgical history. Five of 28 cases have the history of endoscopic treatment and adhesion was observed around the lesion of endoscopic treatment had been performed. There was no significant difference in the average time for reaching at cecum from anal between intestinal adhesion cases and no intestinal adhesion cases.

There were 27 cases that were evaluated as grade 2 or 3 in degree of difficulty for colonoscopy, and intestinal adhesion were observed in fifteen cases of them. We thought that insertion grade2 or 3 may be the bellwether of intestinal adhesion but result showed that insertion grade would not reflect the intestinal adhesion (sensitivity 56.4%, specificity 61.5%, PPV 81.4%, PPV 81.4%, NPV 32.0%).

Conclusion: Difficulties of colonoscopy do not always reflect the intestinal adhesion. But in case of additional intestinal resection for the lesion endoscopic treatment has been performed for colorectal cancer, we should be consider the possibility of intestinal adhesion around the target lesion.

Disclosure of Interest: None declared

P0774 SUBMUCOSAL FIBROSIS AFFECTS THE OUTCOME OF ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) FOR COLORECTAL TUMORS ACCOMPANIED BY FIBROSIS

K. Yanamoto¹, N. Ogasawara¹, A. Shimozato¹, H. Noda¹, Y. Kondo¹, Y. Ito¹, M. Ebi¹, M. Sasaki¹, K. Kasugai¹

¹Aichi Medical University School of Medicine, Nagakute, Japan

Contact E-mail Address: ken1shin2syou3@yahoo.co.jp

Introduction: Endoscopic submucosal dissection (ESD) has recently become a standard treatment for colorectal epithelial neoplasms. Despite the success of ESD, incomplete resection has resulted when it has been applied to laterally spreading tumor (LST) of the colon with submucosal fibrosis which could complicate the separation of the submucosa from the muscular layer. Therefore, ESD for LSTs with submucosal fibrosis might cause high frequencies of incomplete en bloc resection of the tumor and intestinal perforation during ESD. In this study, we aimed to assess the relationship between the outcome of ESD for LSTs and the degree of submucosal fibrosis beneath the tumors. We also evaluated the relationship between the degree of submucosal fibrosis beneath the tumors and the features of LSTs.

Aims & Methods: We evaluated 114 colorectal LSTs larger than 20 mm in diameter between January 2010 and March 2015. LSTs were divided into granular (LST-G) (n=78) and non-granular (LST-NG) (n=36) tumors. LST-Gs were subdivided into homogenous-type tumors (LST-G-homo) (n=34) and nodular-mixed-type tumors (LST-G-mix) (n=44).The degree of submucosal fibrosis beneath the LSTs was determined on the basis of the following original classification system, which was based on the findings obtained at the time of injection of sodium hyaluronate with indigo carmine: F0, no fibrosis, which manifested as a blue transparent layer; F1, mild fibrosis, which appears as a white web-like structure in the blue submucosal layers; and F2, severe fibrosis, which appears as a white muscular like structure without a blue transparent layer in the submucosal layers. The relationship among characteristics of the LSTs, the degree of submucosal fibrosis beneath the LSTs and outcome of ESD for the LSTs were analyzed.

Results: The incidence of F2 fibrosis in LST-G-mix and LSTs-NG was significantly higher than that in LST-G-homo (p < 0.05, compared with F0/1). The tumor locations and sizes did not significantly differ between F2 and F0/F1 fibrosis beneath LSTs regardless of tumor growth patterns. There were no significant differences in the rate of complete en bloc resection and complications such as perforation or delayed bleeding between F2 and F0/1. However, severe bleeding during ESD strongly tended to be related to F2 fibrosis (p=0.06, F2 vs. F0/F1), and the mean duration of the ESD procedure significantly differed between LSTs with severe fibrosis (F2) and LSTs with no or mild fibrosis (F0/ F1) regardless of tumor growth patterns (F2, 269.3 ± 114.4 vs. F0/1, 137.5 ± 80.2 min, p < 0.0001).

Conclusion: The LST-G-mix and LSTs-NG might harbor severe submucosal fibrosis which would predict outcome of ESD for colorectal LSTs. The more advanced the endoscopic submucosal fibrosis, the longer the time required for ESD and the higher the frequency of immediate bleeding during ESD. Further development of endoscopic devices are needed for safe and complete resection of colorectal tumors with severe fibrosis.

Disclosure of Interest: None declared

P0775 NOVEL BIO-MARKER FOR COLORECTAL NEOPLASIA: WHITE OPAQUE SUBSTANCE WITHIN COLORECTAL NEOPLASTIC EPITHELIUM AS VISUALIZED BY MAGNIFYING ENDOSCOPY WITH NARROW-BAND IMAGING

K. Imamura¹, K. Yao², T. Hisabe¹, T. Nagahama¹, F. Hirai¹, M. Nambu³, A. Iwashita³

¹Gastroenterology, ²Endoscopy, ³Pathology, Fukuoka University Chikushi Hospital, Chikushino, Japan

Contact E-mail Address: kentaro2316@ive.jp

Introduction: We previously reported the presence of a white opaque substance (WOS), opaque to the endoscope light, inside the epithelium when we use magnifying endoscopy (ME) to examine gastric epithelial neoplasia (adenomas and carcinomas) and chronic gastritis (intestinal metaplasia). Through further pathohistological study we elucidated that this substance is comprised of minute lipid droplets (LDs) accumulated within the mucosal epithelium of gastric epithelial neoplasia or intestinal metaplasia¹. These minute LDs strongly backscatter the projected light, and are visualized as a white substance. When we examined colorectal neoplastic lesions (adenomas and carcinomas) using ME, we observed WOS as in the stomach. However, it is unclear whether WOS in colorectal epithelial tumors is in fact an accumulation of LDs as in the stomach.

Aims & Methods: Aims: To elucidate whether WOS observed in colorectal epithelial tumors (adenomas and carcinomas) is composed of LDs. We analyzed a continuous series of both 40 WOS-positive and 40 WOS-negative colorectal epithelial tumors. We examined colorectal neoplastic lesions (adenomas and carcinomas), prior to planned treatment, using ME with narrow-band imaging (NBI), determining whether WOS was present in the surface layers of the most anal part of the colorectal epithelial tumor. We took targeted biopsies from this part of the tumor. Biopsy specimens were immediately frozen, slices taken, and the slides were stained for lipids using oil-red O. Slides were examined using light microscopy immediately after staining for the presence of LDs within the neoplastic epithelium. Subsequently, we stained microdroplets of LDs using imunostaining by anti-adiphophilin antibody in formalin-fixed specimen. We investigated the correlation between the presence of WOS as visualized by ME with NBI and the presence of LDs in the histological specimens. And, we compared WOS-positive and WOS-negative about the density of adiphopilin.

Results: We analyzed a continuous series of both 40 WOS-positive and 40 WOS-negative colorectal epithelial tumors. Prevalence of LD as stained by oil red O staining in WOS-positive versus WOS-negative lesions was 47.5% (19/40) and 5% (2/40), respectively (P < 0.001, Fisher's exact test). Furthermore, WOS coincided with the expression of adipophilin. Namely, prevalence of LD as stained by anti-adiphophilin antiboy in WOS-positive versus WOS-negative lesions was 100% (40/40) and 62.5% (25/40), respectively (P < 0.001, Fisher's exact test). Mean density of adiphopilin was significantly greater in WOS-positive (10.8 ± 8.7 %) than in WOS-negative lesions (4.1 ± 4.1 %; P < 0.001).

Conclusion: LDs do not accumulate in the normal colorectal epithelium. However, this study elucidated for the first time that endoscopically visualized WOS may be composed of LDs accumulated in colorectal epithelium. This phenomenon has the potential to be a new biomarker for the pathology and diagnosis of colorectal neoplasia.

Disclosure of Interest: None declared

P0776 TRANSLATION AND CULTURAL ADAPTATION OF THE NATIONAL SURVEY OF MEDICAL DECISIONS QUESTIONNAIRE FOR COLORECTAL CANCER SCREENING FOR USE IN THE SCREENING OF SWEDISH COLON STUDY (SCREESCO)

K. Stake-Nilsson¹, A. Jervaeus², R. Hultcrantz³, K. Fritzell², Y. Wengström²

¹Department of Health and Caring Sciences, University, Gavle, ²Department of Neurobiology, Care Sciences and Society, ³Department of Medicine, Karolinska Institute, Stockholm, Sweden

Contact E-mail Address: ksn@hig.se

Introduction: Colorectal cancer (CRC) is one of the most common cancers in Sweden and CRC screening is a preventive action. At present, Sweden is running a national randomized study Screening of Swedish Colons (SCREESCO) to understand the decision to participate in CRC screening.

Aims & Methods: The questionnaire National Survey of Medical Decisions (DECISIONS) was developed for a US population and the aim was to translate and culturally adapt the DECISIONS questionnaire to the Swedish context. A qualitative design inspired by guidelines based on methods for cross-cultural adaptation of questionnaires in the field of psychology and sociology were used. The guideline includes focus group discussions, individual and telephone interviews and Thinking Aloud (TA) sessions to culturally adapt questionnaires.

Results: The questionnaire: National Survey of Medical Decisions (DECISIONS) was translated and culturally adapted. The translation and adaptation process resulted in reformulation and rewording of 29 items, 11 items changed due to wording and two new items were added as a result of the qualitative interviews and group discussions. The present version of the DECISION questionnaire consists of 24 items concerning decision making.

Conclusion: Our study demonstrates the importance of implementing cultural adaptation to ensure the quality of a translated questionnaire and thereby its results. The major cause for removal and changing of items can be explained by different traditions in communicating with the health care system in Sweden and the US, communication about decision-making and how risk for cancer is communicated in general. The results have hopefully produced a questionnaire that can be used to evaluate decision-making in participation in CRC screening in a Swedish population.

Disclosure of Interest: None declared

P0777 SHOULD WE CHANGE THE INTERVAL OF SURVEILLANCE COLONOSCOPY AFTER REMOVAL OF ADENOMATOUS POLYPS IN PATIENTS WITH FAMILY HISTORY OF COLORECTAL CANCER? - RESULTS FROM THE JAPAN POLYP STUDY

K. Hotta¹, T. Matsuda², on behalf of The Japan Polyp Study workgroup, T. Fujii³, Y. Sano⁴, S.-E. Kudo⁵, Y. Oda⁶, K. Kaneko⁷, T. Shimoda¹, Y. Saito², N. Kobayashi⁸, K. Konishi⁹, H. Ikematsu⁷, H. Iishi¹⁰, K. Kobayashi¹¹, Y. Yamaguchi¹, K. Hasuda¹², T. Shinohara¹³, H. Ishikawa¹⁴, Y. Murakami¹⁵, H. Taniguchi², T. Fujimori¹⁶, Y. Ajioka¹⁷, S. Yoshida¹⁸, on behalf of The Japan Polyp Study Workgroup

¹Shizuoka Cancer Center, Shizuoka, ²National Cancer Center Hospital, ³TF Clinic, Tokyo, ⁴Sano Hospital, Kobe, ⁵Showa University Northern Yokohama Hospital, Yokohama, ⁶Oda GI Clinic, Kumamoto, ⁷National Cancer Center Hospital East, Kashiwa, ⁸Tochigi Cancer Center, Tochigi, ⁹Showa University School of Medicine, Tokyo, ¹⁰Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, ¹¹Kitasato University Hospital, Sagamihara, ¹²Hattori GI Clinic, Kumamoto, ¹³Saku Central Hospital, Saku, ¹⁴Kyoto Prefectural University of Medicine, Kyoto, ¹⁵Toho University, Tokyo, ¹⁶Shinko Hospital, Kobe, ¹⁷Niigata University, Niigata, ¹⁸Aomori Prefectural Central Hospital, Aomori, Japan

Contact E-mail Address: k.hotta@scchr.jp

Introduction: The recommended interval of surveillance colonoscopy for patients with adenomatous polyps is based on adenoma histology, size, and number; however, prospective studies on the impact of family history (FH) of colorectal cancer (CRC) are limited.

Aims & Methods: The aim of this study was to assess whether the interval of surveillance colonoscopy after removal of adenomatous polyps for patients with FH of CRC should be changed compared with patients without FH. The Japan Polyp Study (JPS) is a multicenter randomized control trial conducted at 11 participating centers to evaluate follow-up interval after polypectomy. Patients were eligible if they have had two complete colonoscopies (1st- and 2nd-CS: interval; 1 year) as baseline examination with removal of all neoplastic lesions. Following this they were randomly assigned to have follow-up colonoscopy at 1 and 3 yrs or at 3 yrs only. Main outcome measurements in this subanalysis were prevalence of advanced neoplasia (AN: ≥1 cm, villous histology, high-grade dysplasia, or invasive cancer), high-risk adenoma (HRA: AN or ≥3 non-advanced neoplasia) and low-risk adenoma (LRA: 1 or 2 non-advanced neoplasia) detected during 3 yrs after randomization in patients with first degree relatives with CRC.

Results: Among 3,926 patients with no history of FAP, HNPCC, IBD or colectomy, 1,847 patients (Aged 40-49 yrs: 252, 50-59 yrs: 677, 60-69 yrs: 918, mean age 56.0 yrs, 61.4% male) who underwent two-round complete colonoscopy before randomization and follow-up colonoscopy as scheduled were included. Among patients aged 40-49 yrs who had FH of CRC in first degree relatives or not, the prevalence of AN, HRA and LRA were as follows; AN (0%, 0/43: FH+ vs. 1.0%, 2/209: FH-) (P=0.76), HRA (4.7%, 2/43: FH+ vs. 2.9%, 6/209: FH-) (P=0.90), LRA (25.6%, 11/43: FH+ vs. 21.5%, 45/209: FH-) (P=0.56). Among patients aged 50-69 yrs, prevalence of them were; AN (4.1%, 9/220: FH+ vs. 1.5%, 20/1,375: FH-) (P<0.001), HRA (14.5%, 32/220: FH+ vs. 7.9%, 109/1,375: FH-) (P<0.001), LRA (25.9%, 57/220: FH+ vs. 32.3%, 444/1,375: FH-) (P=0.06).

Conclusion: Prevalence of AN and HRA of patients aged 40-49 yrs and 50-69 yrs without FH of CRC was significantly lower than that of 50-69 yrs patients with FH of CRC during 3 yrs follow-up period. Intensive surveillance colonoscopy namely 3-yrs interval after polypectomy should be recommended only for patients aged 50 yrs or older with FH of CRC; in contrast, there was no novel evidence of changing surveillance interval in patients younger than 50 yrs. Whether these results may affect the current surveillance programs remains uncertain and longer follow-up data might be necessary.

Disclosure of Interest: K. Hotta Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan, T. Matsuda Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan, T. Fujii Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan, Y. Sano Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan, S.-E. Kudo Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan, Y. Oda Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan, K. Kaneko Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan, T. Shimoda Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan, Y. Saito Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan, N. Kobayashi Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan, K. Konishi Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan, H. Ikematsu Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan, H. Iishi Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan, K. Kobayashi Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan, Y. Yamaguchi Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan, K. Hasuda Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan, T. Shinohara Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan, H. Ishikawa Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan, Y. Murakami Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan, H. Taniguchi Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan, T. Fujimori Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan, Y. Ajioka Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan, S. Yoshida Financial support for research: Grants-in-Aid for Clinical Cancer Research (13S-8, 16S-33, 20S-12, and 23S-8) from the Ministry of Health, Labour and Welfare, Japan

P0778 FACTORS AFFECTING THE POST COAGULATION SYNDROME AFTER SUBMUCOSAL DISSECTION FOR COLORECTAL TUMORS

K. Sato¹, S. Ito², T. Kitagawa², Y. Nemoto², K. Tominaga², I. Maetani²

¹Department of Gastroenterology, Mizonoguchi Hospital, Teikyo University School of Medicine, Kanagawa, ²Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Ohashi Medical Center, Tokyo, Japan

Contact E-mail Address: koichiro.sato.0320@gmail.com

Introduction: Postplolypectomy coagulation syndrome (PPCS) has symptoms such as localized abdominal pain, fever, leukocytosis, and peritoneal inflammation without perforation, which occur less than 0.1%. However, post coagulation syndrome (PCS) after colorectal endoscopic submucosal dissection (ESD) is not known well. Here, we aimed to assess the clinical outcomes and factors associated with PCS after colorectal ESD.

Aims & Methods: Between January 2010 and July 2014, we performed ESD on 211 consecutive colorectal tumors in 207 patients. We investigated the incidence of PCS after colorectal ESD and conducted multiple logistic regression analysis of the following factors related to PCS after colorectal ESD: age, gender, location, tumor size (< 40 mm vs. ≥ 40 mm), operation time (< 120 min vs. ≥ 120 min), morphology (granular type laterally spreading tumor [LST-G], non-granular type laterally spreading tumor [LST-NG], or protruded type), fibrosis, and paradoxical movement during the procedure. PCS after colorectal ESD was defined as fever (≥ 37.8°C) and abdominal pain or regional rebound tenderness in the absence of perforation during or after ESD.

Results: After exclusion of 4 of 211 cases with perforation, 207 patients were analyzed. In the treated epithelial lesions, 36 cases were located in the rectum (17.4%), 41 cases in sigmoid colon (19.8%), 44 cases in transverse colon (21.3%) and 51 cases in ascending colon (24.6%). PCS after ESD occurred in fifteen cases (7.2%). Of the fifteen cases of PCS, six cases (2.9%) occurred in cecum, four cases (1.9%) in ascending, three cases (1.4%) in transverse and two cases (0.97%) in rectum.

Average tumor size was 30.9 ± 10.5 mm, and the average procedure length was 66.8 ± 45.1 min. The rate of en bloc resection was 96.6%, while that of en bloc curative resection was 87.4%.

Univariate analysis showed that tumor site in the cecum (p=0.0014), tumor size (≥ 40 mm, p< 0.001), loner procedure time ( ≥ 120 min, p< 0.001) during the procedure and severe fibrosis (p=0.0161) were significantly associated with PCS of colorectal ESD.

Multivariate logistic regression analysis revealed that tumor location in the cecum (odds ratio [OR] 17.58; 95% confidence interval [CI] 2.32–210.9, p=0.0043), a tumor size exceeding 40 mm (OR 6.43 [95% CI 1.37-34.02], p=0.019) contributed to PCS after colorectal ESD. A trend for PCS after the ESD procedure in the group which experienced longer procedure time during the procedure was also noted (p=0.0619).

Conclusion: Tumors located in cecum, larger tumor size more than 40mm were independent factors contributing to the PCS of colorectal ESD.

Disclosure of Interest: None declared

P0779 DOES COLORECTAL ADENOMA INCREASE THE RISK OF GALL BLADDER POLYP?

K. O. Kim¹, S. B. Kim¹, K. H. Kim¹, S. H. Lee¹, B. I. Jang¹, T. N. Kim¹

¹Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Republic of Korea

Contact E-mail Address: cello7727@naver.com

Introduction: Colorectal adenoma and gallbladder (GB) polyp share many risk factors. However studies concerning the association between colorectal adenoma and GB polyp has been rare.

Aims & Methods: The aims of this study were to evaluate whether colorectal adenoma increases the risk of GB polyp and analyze the risk factors associated with GB polyp. Health examinees who underwent both hepatobiliary sonography and colonoscopy in Yeungnam University Hospital health promotion center from January 2010 to December 2013 were included. Subjects with previous history of cholecystectomy and without pathologic report of colorectal polyp were excluded. To eliminating the confounding factors of GB polyp, age, gender and BMI was matched using propensity score. The clinical characteristics, colonoscopy and ultrasonographic findings of the subjects were reviewed and compared between colorectal adenoma and non-adenma group retrospectively.

Results: Among 4373 subjects, colorectal adenoma was detected in 1453 (33.2%) and colorectal cancer in 11 (0.3%). There were significant differences in age, gender and presence of fatty liver between subjects with or without colorectal adenoma. GB polyp was noted in 362 (8.3%) cases. After using propensity score matching, number of subjects in each groups with or without colorectal adenoma was 1453. Subjects with colorectal adenoma only or with concomitant colorectal cancer had tendency of more GB polyps than those without (145 (10.0%) vs 116 (8.0%), (p=0.060)). Although mean age of the subjects was not significantly different depending on the presence of GB polyp, male was more common in subjects with GB polyp (218 (83.5%) vs 1976 (74.7%), p=0.002). There was no significant difference in presence of GB stone and fatty liver and level of BMI and total cholesterol between two groups. Five (0.1%) subjects underwent operation of GB polyp and diagnosed as cholesterol polyp and/or adenoma. By multivariate analysis, the risk of GB polyp was higher in subjects with colorectal adenoma, however, it failed to show clinical significance (OR 1.28, 95% CI 0.99-1.65, p=0.06) and the only significant risk factor of GB polyp was male gender (OR 1.72, 95% CI 1.22-2.40, p=0.002).

Conclusion: Presence of colorectal adenoma was associated with higher tendency for GB polyp although it could not show statistical significance. Meticulous examination with ultrasonography of GB should be considered especially in male subjects with colorectal adenoma not to miss the GB polyps. Further studies concerning the common pathogenesis associated with both colorectal adenoma and GB polyp are warranted.

Disclosure of Interest: None declared

P0780 DIAGNOSTIC VALUE OF FUJINON INTELLIGENT COLOR ENHANCEMENT (FICE) TECHNOLOGY WITH AND WITHOUT MAGNIFICANTION TO DIFFERENTIATE BETWEEN HYPERPLASTIC AND ADENOMATOUS LESIONS ACCORDING TO THE NICE CLASSIFICATION - A PROSPECTIVE, RANDOMIZED, CONTROLLED STUDY

L. Madacsy¹, G. Gyimesi¹, I. Hritz¹, P. Hausinger¹, T. Velkei¹, B. Gellert², Z. Dubravcsik¹, A. Szepes¹

¹Department of Gastroenterology, Bacs-Kiskun County Hospital, Kecskemet, Hungary, Kecskemet, ²Department of Gastroenterology, Semmelweis University, Budapest, Hungary

Contact E-mail Address: endomabt1@gmail.com

Introduction: According to the resect-and-discard strategy the histological type of the colonic polyps (adenomatous vs. non-neoplastic or hyperplastic) is predicted in vivo by an appropriate endoscopic method, and based on this decision certain postpolypectomy pathologic specimens can be discarded rather than sent for histological assessment. The purpose of this prospective, non-interventional study was to validate the Narrow Band Imaging International Colorectal Endoscopic (NICE) classification for differentiating hyperplastic and adenomatous polyps by using Fuji Intelligent Color Enhancement (FICE) technology with high-definition with and without optical magnification.

Aims & Methods: 117 patients referred for outpatient colonoscopy were prospectively enrolled. All endoscopies were performed by experienced endoscopists. 61 patients were randomized to investigate with the Fujinon EC-600WM and 56 patients to investigate with the EC-600ZW/L series. In order to create a video-library of endoscopic cases, patients with at least one histologically verified polyp were included. A short HD video-clip (around 15-20 seconds) of each polyp and a HD DICOM still picture both at white-light and at FICE-virtual chromoendoscopy were recorded and stored in an anonymized video database. Histopathology of the lesions were confirmed by the blinded pathological evaluation of endoscopic resection, polypectomy or biopsy specimens. Finally NICE classification with FICE and histopathological results were compared.

Results: In the 117 patients we detected 247 polyps, all of them were endoscopically removed and sent to histological assessment. The average size of the polyps were 4,1 mm. According to the histopathological results, six early adenocarcinomas, 148 adenomas and 93 hyperplastic polyps were detected. There was a complete agreement between the NICE classification with FICE technology and histological results in 217 polyps (87,9%). 17 polyps classified as NICE type II despite non-neoplastic histology (6,9% false positive), whereas 14 polyps were classified as NICE type I despite adenomatous histology (5,7% false negative). No significant differences in the accuracy of NICE classification between standard and zoom HD colonoscopy compared to histology were detected.

Conclusion: FICE virtual chromoendoscopy in combination with HD colonoscopy with or without magnification is a promising tool for the differentiation of neoplastic from non-neoplastic colorectal polyps. High confidence predictions for adenomas such as NICE classification may provide precise diagnostic tool for real-time endoscopic diagnosis of neoplastic polyps.

Disclosure of Interest: None declared

P0781 LONG-TERM FOLLOW-UP AFTER ENDOMUCOSAL RESECTION FOR COLORECTAL POLYPS: A RETROSPECTIVE AUDIT OF EXPERIENCE AT A LARGE DISTRICT GENERAL HOSPITAL

J. Aldridge¹, T. Murugesan¹, L. Burke¹, D. Vani¹, S. Shah¹

¹Gastroenterology, Pinderfields General Hospital, Wakefield, United Kingdom

Contact E-mail Address: syed.shah@midyorks.nhs.uk

Introduction: Endomucosal resection (EMR) of colorectal polyps at lower GI endoscopy is becoming increasingly important, offering an effective means of removing large, obstinate polyps without resorting to surgery¹. There is ample evidence on short-term recurrence post EMR but longer term data is missing^1,2. We analysed our experience to fill this gap and provide follow-up data at 3 and 5 years post EMR.

Aims & Methods: Retrospective analysis was performed on endoscopy reports for all EMRs performed at lower GI endoscopies during a one year period in 2010 at a non-tertiary GI endoscopy unit. Reports were accessed from the hospital endoscopy reporting system (HICSS) and analysed for details of the EMR performed and follow up endoscopies for recurrence at the site of initial EMR. The location, size and morphology of polyp was recorded along with EMR details including completeness and need for APC. Polyp recurrence at subsequent endoscopies up to 5 years was also recorded.

Results: 188 lower GI endoscopies with EMR were performed. After exclusion for malignancy requiring surgery, incomplete follow up, polyp size <1cm, 111 were analysed. Duration of follow up ranged from 3 to 60 months with a mean follow up of 32 months (median 35 months). Of the 111 polyps, 59% were 1-2cm, 36% 2-5cm, 5% >5cm. Location was in the left colon in 59% of polyps and right-sided in 41%. The majority of polyps regardless of size were sessile (75%) with the remainder being flat (19%) or sub-pedunculated (6%).

Follow up endoscopy	6 months	1 year	3 years	5 years
No. performed	53	68	49	24
Recurrence (%)	7/53 (13)	5/68 (7)	5/51 (10)	0/25 (0)

Conclusion: This study confirms EMR is an effective alternative to surgery in the management of difficult colonic polyps. Our short-term recurrence rates are lower than those previously documented² and these low rates are maintained at long-term follow-up with a mean follow up duration of 32 months. Our results favour the confident use of EMR in the eradication of large and/or complex colonic polyps to achieve low long-term recurrence rates.

Disclosure of Interest: None declared

P0782 BOWELSCOPE SCREENING- RESULTS FROM THE PILOT SITES

L. J. Neilson¹², R. Bevan¹², C. Nickerson³, J. Patnick³, R. Loke⁴, B. P. Saunders⁵, J. Stebbing⁶, R. Tighe⁷, A. Veitch⁸, C. J. Rees¹², on behalf of NHS Bowel Cancer Screening Evaluation Group

¹Gastroenterology, South Tyneside District Hospital, South Shields, ²Northern Region Endoscopy Group, Newcastle upon Tyne, ³NHS Cancer Screening Programmes, Public Health England, Sheffield, ⁴West Kent & Medway BCSC, Tunbridge Wells, ⁵St Marks BCSC, Harlow, ⁶Surrey BCSC, Guildford, ⁷Norwich BCSC, Norwich, ⁸Wolverhampton BCSC, Wolverhampton, United Kingdom

Contact E-mail Address: laura.neilson@stft.nhs.uk

Introduction: A large UK study of single flexible sigmoidoscopy with adenoma clearance in patients aged 55-64, demonstrated a reduction in CRC incidence by 23% and mortality by 31% in intention-to-treat analyses.¹ This provided the rationale for provision of a new arm of the Bowel Cancer Screening Programme (BCSP), offering a single flexible sigmoidoscopy (FS) to all 55 year olds in England, known as BowelScope screening. BowelScope was introduced to 6 pilot sites, beginning in May 2013. It is to be rolled out across the country by 2016.

Aims & Methods: We aim to describe the findings, in terms of procedural data, from the first year of BowelScope screening at the pilot sites.

Data were obtained from the Bowel Cancer Screening System database for all participants who underwent FS between May 2013-May 2014. Procedural data were recorded, including entonox use, adenoma detection rate (ADR), cancer detection, complications and colonoscopy conversion rates.

Results: Overall uptake was 44.1%. 1 cancer was detected. Mean ADR was 9.2%. The mean number of patients requiring colonoscopy conversion was 4.2%. Mean complication rate was 0.1%, including bleeding, discomfort, difficult polyp excision and unwell patient. There was wide variation in entonox use. (Table 1)

Abstract number: P0782

Centre	Uptake (%)		Procedures (n)	Endoscopists (n)	Entonox (n(%))	ADR (%)	Cancer (n)	Colonoscopy Required (n(%))	Complications (n)
Male	Female
1	51.6	48.4	2381	11	254 (10.7)	9.4	0	67 (2.8)	1
2	40.9	35.1	901	8	149 (16.5)	11.1	0	53 (5.9)	4
3	43.2	41.7	2062	15	110 (5.3)	10.2	0	126 (6.1)	2
4	52.3	50.2	712	5	22 (3.1)	9.0	0	26 (3.7)	0
5	49.3	45.9	1437	11	56 (3.9)	7.6	0	56 (3.9)	0
6	39.7	35.7	1326	11	57 (4.3)	7.6	1	46 (3.5)	1
Total	45.6	42.4	8819	61	648 (7.3)	9.2	1	374 (4.2)	8 (0.1%)

Conclusion: Uptake has improved since the six month data were presented but remains lower than for the FOB arm of the BCSP, and varies between sites. The ADR is 9.2% (range 7.6% - 11.1%). This is lower than reported in the UK FS screening trial (12.1%¹), however ADR calculations in BowelScope do not include adenomas not removed at FS but removed later at colonoscopy, whereas the FS trial did. The ADR is comparable to the BowelScope pathfinder project (9.6%²).

Further work is necessary to explore the variation in uptake rates. Variation in ADR exists between centres. Further analysis of endoscopist factors and patient groups may explain this. Entonox use varies widely but does not appear to correlate with ADR- further work may be required to investigate this.

Disclosure of Interest: None declared

P0783 HIGH PREVALENCE OF SYNCHRONOUS AND METACHRONOUS COLONIC NEOPLASIA AND OTHER MALIGNANT NEOPLASM AMONG PATIENTS WITH TRADITIONAL SERRATED ADENOMAS

L. Pereyra¹, E. J. Gómez¹, M. Omodeo¹, R. González¹, J. M. Mella¹, G. N. Panigadi¹, C. Fischer¹, S. C. Pedreira¹, L. A. Boerr¹, D. G. Cimmino¹

¹Gastroenterology and Endoscopy Unit, Hospital Alemán, Buenos Aires, Argentina

Contact E-mail Address: lisandro_pereyra@hotmail.com

Introduction: The traditional serrated adenoma (TSA) is the least frequent colorectal serrated polyp.The prevalence of high-grade dysplasia (HGD) and adenocarcinoma in these polyps as well as association with colorectal neoplasia and malignant neoplasia has not been established.

Aims & Methods

Aim: To determine the prevalence of HGD and adenocarcinoma and to establish the association with synchronous (SNL) and metachronous neoplastic lesions (MNL) and other malignant neoplasm among patients with traditional serrated adenomas (TSA).

Methods: Reports from patients undergoing colonoscopy and polypectomy from January 2003 to September 2014, were retrospectively obtained from the electronic database of a teaching hospital. Personal and family history of colorectal cancer (CRC) and malignant neoplasm were consigned from medical records. TSA diagnosis was based on the presence of luminal serration, cytoplasmic eosinophilia and the presence of ectopic crypt foci. SNL were defined by adenomas, sessile serrated adenomas (SSA), cancer or advanced neoplastic lesions (ANL) (>1cm, HGD or >75% of villous component) in the same colonoscopy. Those lesions appearing after 12 months of index colonoscopy during surveillance were considered MNL. A multivariate analysis was performed, looking for independent predictors of HGD, cancer, SNL and MNL in patients with TSA.

Results: During the analyzed period a total of 101 STA were diagnosed in 89 patients. The prevalence of STA was 0.45% (101/ 22000 colonoscopies). The mean age was 62 years old (range: 32-90) and 55% of patients were men. A personal and family history of CRC was present in 4/89(4.5%) and 12/89 (13%) respectively. Personal history of malignant neoplasm was present in 8/89 (9%) patients (4/8 lung cancer and 4/8 skin cancer).Familial adenomatous polyposis had been diagnosed in 1/89(2%) patients and 7/89 (9%) met the WHO diagnostic criteria for serrated polyposis syndrome. Regarding TSA characteristics, average polyp size was 9.61 mm (range 5-45) and the most frequent location was left-colon 89/101(88%). Polyps more frequent morphology were sessile 63/101(62 %) and pedunculated 33/101( 33%). HGD was present in 6/101(6%). Regarding SNL 39% presented adenomas, 35% SSA, 19% ANL, and 4.5% adenocarcinoma on index colonoscopy. During surveillance colonoscopy 25% presented SSA, 31% adenomas, 44% ANL and 0% adenocarcinoma. Multivariate analysis revealed that polyp size >20mm was the only independent predictor of HGD (OR 25.14 CI 3.10-249, p 0.0001). We didn´t find independent predictors for synchronous or metachronous neoplastic lesions.

Conclusion: We found low prevalence of TSA similar to reported. The frequent association of these lesions with synchronous and metachronous colonic neoplasia, intestinal polyposis syndromes and other malignant neoplasm, highlights the importance of detecting these lesions during routine colonoscopy.

Disclosure of Interest: None declared

P0784 A SECOND LOOK COLONOSCOPY INCREASES THE DIAGNOSTIC YIELD FOR SERRATED POLYPOSIS SYNDROME IN SCREENING POPULATION

L. Rivero-Sánchez¹², M. Lopez-Ceron¹³, S. Carballal¹³, L. Moreira¹, X. Bessa⁴, C. Hernandez⁵, A. Serradesanferm⁶, A. Pozo⁶, T. Ocaña¹, M. Cuatrecasas⁷, J. Llach¹, A. Castells¹, F. Balaguer¹, M. Pellise¹, on behalf of Procolon

¹Gastroenterology, Hospital Clínic of Barcelona, ²Fundació Clínic per a la Recerca Biomédica (FCRB), ³Institut dÍnvestigacions Biomédiques August Pi i Sunyer (IDIBAPS), ⁴Gastroenterology, ⁵Espidemiology and Evaluation Department, Hospital del Mar, ⁶Preventive Medicine and Hospital Epidemiology Department, ⁷Pathology Department, Hospital Clínic of Barcelona, Barcelona, Spain

Contact E-mail Address: mpellise@clinic.ub.es

Introduction: Serrated polyposis syndrome (SPS) is often under-diagnosed in a single colonoscopy. The low sensitivity of diagnostic criteria for SPS could impair the follow-up approach in high-risk patients who have not yet met them. Current surveillance recommendations concerning serrated polyps (SP) are insufficient.

Aims & Methods: We aimed to assess the yield of a second look colonoscopy (SLC) to diagnose SPS after a screening colonoscopy and to determine the optimal SP-threshold to indicate it.

From January 2010 to July 2013, individuals with ≥1 SP ≥5 mm proximal to splenic-flexure or ≥10 mm along the colon after a screening colonoscopy were retrospectively evaluated. Despite the standard surveillance recommendations based on adenomas, an early SLC was empirically scheduled to patients with concomitant SP to rule out SPS. SLC was performed with a special aim at detecting SP.

Results: 196/3444 patients fulfilled selection criteria. At screening colonoscopy, 11 were already diagnosed of SPS. Amongst the 185 remaining patients, 71 underwent SLC in 11.9 ± 1.7 months. According to SLC findings, individuals were grouped into: 1) SPS: 20 (28%) representing a 182% increase compared to baseline-colonoscopy diagnosis, 2) SPS-like (those with a high burden of SP and almost fulfilling SPS criteria): 15 (21%) and 3) Sporadic-SP: 36 (51%). SPS and SPS-like were considered High-Risk group. Independent colonoscopy baseline and individual predictive characteristics of High-Risk were: presence of ≥5 proximal-SP (OR 4.04 [1.2-13.5], p=0.023),  ≥2 sessile serrated polyps ≥10mm (OR 12.42 [1.39-110.72], p=0.024) and high-definition endoscopy and/or conventional/virtual chromoendoscopy use at SLC (OR 7.43 [2.01-27.49], p=0.003).

Conclusion: A SLC within one-year doubles the number of patients diagnosed with SPS after a screening colonoscopy. The presence of ≥5 proximal-SP or ≥2 sessile serrated polyps ≥10mm at baseline-colonoscopy is an optimal threshold to indicate a SLC. SLC has to be performed preferably using advanced endoscopic techniques. These findings provide rationale to adjust surveillance recommendations in individuals with concomitant SP.

Disclosure of Interest: L. Rivero-Sánchez: None declared, M. Lopez-Ceron: None declared, S. Carballal: None declared, L. Moreira: None declared, X. Bessa: None declared, C. Hernandez: None declared, A. Serradesanferm: None declared, A. Pozo: None declared, T. Ocaña: None declared, M. Cuatrecasas: None declared, J. Llach: None declared, A. Castells: None declared, F. Balaguer: None declared, M. Pellise Consultancy: Norgine

P0785 THE NBI TECHNOLOGY COULD INCREASE THE OPTICAL DIAGNOSIS OF THE GASTROINTESTINAL GRAFT-VERSUS-HOST DISEASE

A. Maimone¹, C. Giardini², A. de Leone¹, M. T. Fabi¹, P. Lorenzini³, M. L. Bianchi¹, S. Fiori¹, A. Isidori², G. Visani², L. De Luca¹

¹Gastroenterology and Endoscopy Unit, ²Hematology and Bone Marrow Transplant Centre, ³Department of Pathological Anatomy, A.O. “ Ospedali Riuniti Marche Nord", Pesaro, Italy

Contact E-mail Address: antonellamaimone@yahoo.it

Introduction: Athough graft versus host disease (GVHD) is a complication relatively common after allogenic hematopoietic stem cell transplantation (HSCT), it infrequently evolves in severe gastrointestinal (GI) complications. The diagnosis of GI-GVHD is often elusive, due to variability of the clinical presentation and it is based upon histologic findings. The endoscopic intestinal lesions are macroscopically pleomorphic (i.e. mucosal erytema, aphthous ulcerations) and can be patchy or absent in early phases of the disease. The Narrow Band Imaging (NBI) is a simple “push-on-a button” technique that enhances mucosal and vascular details without the use of dyes, and has proven to be superior to only High-Resolution Endoscopy (HRE).

Aims & Methods: The aims of this pragmatic trial were to explore the role of NBI system in the diagnosis of GI-GVHD. Seventeen of 51 patients (33%) which received allogenic HSCT at Bone Marrow Transplant Unit of Pesaro, presented unexplained diarrhoea at risk for acute GI-GVHD. The median time from transplantation was 40 days and the diagnosis work-up for infection causes resulted negative. These patients underwent to colonoscopy using the Evis Exera II system (Olympus Medical Systems, Tokyo, Japan) and a High-Resolution endoscope (CF-H180AI/L), integrating NBI system by only pushing a button. The multiple biopsies of the ileum, right, transverse, left and rectosigmoid colon were performed by the same operator during each procedure. The histological diagnosis was carried by a skilled pathologist

Results: The histological diagnosis of intestinal GVHD was confirmed in 7/17 patients (41%). HRE have shown macroscopic findings in 2 patients, characterized by extensive mucosal hyperemia, nodularity, hemorragic spots, patchy erosions and multiple shallow ulcers. The NBI system identified minute changes of the mucosal surface as pattern thinning and microvascular network irregularities in 5 patients (M/F 3:2, mean age 39), in whom HRE was normal (Table 1).

Table 1.

The relationship between histological evaluation and endoscopic findings of HRE and NBI technologies for GI-GVHD diagnosis.

Histological Diagnosis		Endoscopic Findings
N. Patients		HRE	NBI
GVHD	7	2	7
Normal	10	15	10

Conclusion: The NBI system could help to identify minute abnormalities suspicious for GI-GVHD, such as alteration of vascular pattern and mucosal micro-nodularity, not detected by HRE. This tool could increase the yield of endoscopic diagnosis of GI-GVHD by targeted biopsy compared to random biopsies at HRE. Further evaluation may be need to establish the correlation between endoscopic and histological findings.

Disclosure of Interest: None declared

P0786 BLUE LASER IMAGING: A NOVEL ENDOSCOPIC TOOL FOR PRECISE EVALUATION OF VASCULAR PATTERN OF COLORECTAL LESIONS

C. R. Teixeira¹, L. F. Figueiredo¹, M. Bonotto¹, J. Pereira-Lima¹, N. H. V. Coelho¹, M. Maia¹, C. R. F. Rodrigues¹, L. Conrado¹

¹Endoscopic Unit, FUGAST, Porto Alegre, Brazil

Contact E-mail Address: texcla@terra.com.br; luciana.gastro@gmail.com

Introduction: A new system using a laser light source, Blue Laser Imaging (BLI-Lasereo by Fujifilm), has been developed allowing an in vivo endoscopic observation of the surface and microvascular pattern of lesions. Colonoscopy with BLI-Lasereo and magnifying zoom enable the characterization of the fine superficial capillary pattern of normal mucosa and of colorectal lesions. The endoscopic distinction between the different capillary pattern can contribute to the differential diagnosis among normal, hyperplastic, serrated and other neoplastic lesions.

Aims & Methods: Applying this latest technology, the objective of this study is to evaluate the accuracy of the capillary-vessel pattern classification of colorectal lesions diagnosed during routine colonoscopy using BLI and magnifying zoom imaging.

A total of 91 colorectal lesions in 42 patients (23 men) were prospectively examined using Kudo's pit pattern classification and capillary-vessel pattern according to our previous published classification ¹. All lesions were endoscopically or surgically resected In summary, the capillary pattern was divided into 5 subtypes according to the number, morphology and architecture of the fine blood vessels. The presumptive endoscopic diagnosis of the lesions were correlated with the histopathologic findings, determining the sensitivity, specificity and accuracy of this method.

Results: The overall accuracy of the fine blood vessel classification by BLI and magnification in differentiating neoplastic and non-neoplastic colorectal lesions was 95.6% (87/91 lesions). The sensitivity, specificity, positive predict value and negative predict value of the capillary pattern classification for distinguishing neoplasia from non-neoplasia were, respectively, 98.5%, 90.9%, 97.1% and 90.9%

Conclusion: The endoscopic classification of the superficial capillary-vessel pattern of colorectal lesions using BLI - Lasereo technology is an accurate method to predict the histopathologic diagnosis. BLI - Lasereo system is a very promising technology for precise evaluation of fine blood vessel pattern.

Disclosure of Interest: C. Teixeira Financial support for research: Research grant, Consultancy: Speaker, L. Figueiredo: None declared, M. Bonotto: None declared, J. Pereira-Lima: None declared, N. H. Coelho: None declared, M. Maia: None declared, C. R. Rodrigues: None declared, L. Conrado: None declared

P0787 ENDOSCOPIC MUCOSAL RESECTION OF LARGE COLORECTAL POLYPS: LONG-TERM PROSPECTIVE EVALUATION OF EFFECTIVENESS AND COMPLICATIONS

L. Elvas¹, M. Areia¹, D. Brito¹, R. Carvalho¹, S. Alves¹, S. Saraiva¹, A. T. Cadime¹

¹Gastroenterology, Portuguese Oncology Institute - Coimbra, Coimbra, Portugal

Contact E-mail Address: luisandreelvas@gmail.com

Introduction: Endoscopic mucosal resection (EMR) is a very important therapeutic procedure for large sessile and flat colorectal polyps. The aim of the study was to prospectively evaluate the success, complications and recurrence with EMR.

Aims & Methods: Prospective cohort study of patients referred for EMR of colorectal polyps ≥20mm at our gastroenterology department, between June of 2008 and February of 2015. Inject and cut technique was used and argon-plasma coagulation was applied in resection margin if any remnant tissue was suspected. Patients’ and lesions’ characteristics were collected, as well as complications and recurrence at 3, 12, 36 and 60 months. Statistical analysis was performed by logistic regression.

Results: A total of 155 colorectal polyps were removed in 148 patients (56% males; mean age 70 ± 10 years). Median polyp size was 30mm (20; 40) and 65% were sessile while 35% were flat polyps. Almost half of the lesions (47%) were located in rectum or sigmoid colon.

Median follow-up time was 24 months (12;41). Piecemeal resection was performed in 86%.

Recurrence rate was 19% (26/136) at 3 months, 6.3% (8/127) at 12 months and 2.7% (2/73) at 36 months. There was no recurrence after 60 months (0/36). Three polyps (1.9%) required surgery after non-complete resection/recurrence. The complication rate was 8.4% (13/155) and all complications were managed without surgery: bleeding – 10 (2 immediate and 8 delayed); perforation – 1 (0.6%); post-polypectomy electrocoagulation syndrome – 1; rectal ulcer – 1. Logistic regression identified distal rectal location of the polyp as the only risk factor for recurrence (OR 3.8, IC 95%: 1.5-10.2).

Conclusion: In our experience, EMR is a safe procedure for removing large colorectal polyp and all procedure-related complications were managed without surgical intervention. The possibility of recurrence implies an endoscopic long-term follow-up and, after 5 years, 98% of our patients were cured only with endoscopic therapy.

Disclosure of Interest: None declared

P0788 IMPACT OF PERSONALIZED PATIENT EDUCATION ON BOWEL PREPARATION FOR COLONOSCOPY – PROSPECTIVE RANDOMIZED CONTROLLED TRIAL

L. Elvas¹, D. Brito¹, M. Areia¹, R. Carvalho¹, S. Alves¹, S. Saraiva¹, A. T. Cadime¹

¹Gastroenterology, Portuguese Oncology Institute - Coimbra, Coimbra, Portugal

Contact E-mail Address: luisandreelvas@gmail.com

Introduction: An adequate bowel preparation is one of the most important quality factors of colonoscopy.

Aims & Methods: Our goal was to analyze the impact of personalized patient education on bowel preparation cleansing for colonoscopy.

We performed a single-blinded, single-center, prospective randomized controlled trial, where patients were allocated to “control” group, which received predefined oral and written information on bowel preparation from the gastroenterologist, or “intervention” group, that also had a 20-minute appointment with a nurse, receiving personalized education on all preparation steps. Primary outcome was the quality of bowel preparation (Aronchick Scale).

Results: A total of 229 patients were randomized, 113 to “control” group and 116 to “intervention” group. In intention-to-treat analysis, bowel preparation was “adequate” in 63% of colonoscopies of “intervention” group and in 40% of “control” group (p=0.001). Subgroup analysis showed a significant impact of personalized education in patients under 65 years (67% vs. 35%; p < 0.001), males (60% vs. 33%; p=0.003), those with higher educational levels (68% vs. 37%; p=0.002), living in urban areas (68% vs. 40%; p=0.004) and with previous colonoscopy (68% vs. 40%; p=0.001). Risk factors for “inadequate” preparation were: male gender (OR=2.1; 95% CI 1.1-4.1), diabetes mellitus (OR=3.8; 1.2-11.6), chronic constipation (OR=3.7; 1.7-8.2), absence of prior abdominal surgery (OR=2.2; 1.2-4.1) and absence of personalized patient education (OR=2.5; 1.4-4.4).

Conclusion: Personalized patient education on bowel preparation for colonoscopy significantly improved the quality of bowel preparation. We believe it should be applied in every gastroenterology department as it could improve the quality of colonoscopy.

Disclosure of Interest: None declared

P0789 ENDOSCOPIC POLYPECTOMY OF COLONIC POLYPS – PROSPECTIVE ANALYSIS OF COMPLICATIONS

L. Elvas¹, D. Brito¹, R. Carvalho¹, M. Areia¹, S. Alves¹, S. Saraiva¹, A. T. Cadime¹

¹Gastroenterology, Portuguese Oncology Institute - Coimbra, Coimbra, Portugal

Contact E-mail Address: luisandreelvas@gmail.com

Introduction: Endoscopic polypectomy of colonic polyps decreases morbidity and mortality of colorectal cancer. Bleeding and colonic perforation are the most common complications of this technique.

Aims & Methods: Our aim was to evaluate the complication rate of endoscopic polypectomy.

We conducted a prospective registry, from 2009 to 2015, of polypectomy procedures performed at our endoscopy unit and its complications. An appointment was scheduled around 1 month after the procedure so that every patient could report any delayed complications. Complication rate and risk factors were analyzed. Statistical analysis was performed with chi-square test and logistic regression.

Results: We included 2416 polypectomies (6.4% endoscopic mucosal resections) in 1052 patients (63% males; mean age 63 ± 11 years). Mean time for the post-polypectomy appointment with gastroenterologist: 44 ± 24 days. Polyp characteristics: mean size – 8.8 ± 7.0mm; left-sided – 61%; sessile type – 71%. Complication rate per-polyp was 1.4%: bleeding – 1%; perfuration – <0.1%; other complications – 0.3%. All complications were managed without surgery. Nineteen patients (0.8%) required in-hospital stay. Delayed complications occurred 4.1 ± 3.7 days after polypectomy. From the 23 cases of bleeding, 11 needed endoscopic hemostasis treatment and 4 required red cell transfusion. Delayed bleeding probability increased with polyp size ≥20mm (3.4% vs. 0.7%, p < 0.001), was higher in sessile versus pedunculated polyps (1.1% vs. 0.6%, p=0.21) and in patients under 65 years-old (1.2% vs. 0.7%, p=0.19). In multivariate logistic regression only polyp size reached statistical significance, OR 4.9 (IC 95%: 2-12).

Conclusion: Complication rate of our series is similar to published data. We point out that there were no deaths and all complications were managed without surgery.

Disclosure of Interest: None declared

P0790 DISTANCE FROM RECTAL AND SIGMOID TUMORS TO ANAL VERGE – EVERY CENTIMETRE COUNTS!

L. Elvas¹, D. Brito¹, M. Areia¹, S. Alves¹, S. Saraiva¹, A. T. Cadime¹

¹Gastroenterology, Portuguese Oncology Institute - Coimbra, Coimbra, Portugal

Contact E-mail Address: luisandreelvas@gmail.com

Introduction: An exact characterization of the distance from distal end of rectal and sigmoid tumours to anal verge is essential for an adequate staging and treatment decision, concerning neoadjuvant therapies and different types of surgery.

Aims & Methods: Our aim was to compare the measures from colonoscopies performed in ambulatory centre outside our hospital against a flexible sigmoidoscopy performed at our gastroenterology department.

We performed a prospective comparative study of patients with rectal and distal sigmoid malignant neoplasia, who were submitted to colonoscopy examination outside our institution and to flexible sigmoidoscopy at our endoscopy unit, to determine the distance from distal end of the lesion to the anal verge. The distance measured in pelvic magnetic resonance imaging (MRI) was used as reference. Statistical analysis performed with Mann-Whitney and Chi-square tests and Spearman correlation coefficient.

Results: We included 32 lesions from 32 patients (53% female; mean age 67 ± 12 years). In 5 (16%) of the ambulatory colonoscopies the distal end of the lesion was not reported. The median value of the difference between measured distances outside and inside our hospital department was 3.0cm (1;6). MRI and both endoscopic procedures were available in 22 of the 32 patients. Spearman correlation coefficient between endoscopic procedures and MRI was 0.68 for ambulatory and 0.93 for in-hospital flexible sigmoidoscopy. Comparing each procedure with MRI, there were statistically significant differences (ambulatory vs. MRI – 3.0cm; in-hospital vs. MRI – 0.0cm; p=0.007). When using MRI as reference, the differences between distance to the anal verge would change the staging or treatment of a lesion in 5% of in-hospital exams vs. 37% of ambulatory colonoscopies (p=0.03). In the latter, 7 out of 22 (32%) rectal tumours were wrongly classified as sigmoid (above 15cm from anal verge), which could change the staging and neoadjuvant therapeutic options, and 1 (5%) distal rectal tumour reported as proximal, which could be immediately directed to a centre with expertise in minimally invasive rectal surgical interventions.

Conclusion: Reporting the exact distance from distal end of rectal and sigmoid tumours to anal verge is important but it is endoscopist-dependent. A precise measure of these distances allows better staging options and adequate treatment decision.

Disclosure of Interest: None declared

P0791 CAN WATER EXCHANGE IMPROVE COMFORT DURING COLONOSCOPY WITHOUT SEDATION IN ELDERLY PATIENTS?

M. Arai¹, K. Okimoto¹, H. Ishigami¹, T. Taida¹, A. Oyamada¹, S. Minemura¹, K. Saito¹, D. Maruoka¹, T. Matsumura¹, T. Nakagawa¹, T. Katsuno¹, K. Yamaguchi², O. Yokosuka¹

¹Gastroenterology, Chiba Univeristy Hospital, ²Gastroenterology, Chiba Foundation for Health Promotion and Disease Prevention, Chiba, Japan

Contact E-mail Address: araim-cib@umin.ac.jp

Introduction: Previous studies have shown that colonoscopy with water exchange technique is superior to air insufflation in attenuating insertion pain and that it is difficult for trainee colonoscopists to perform colonoscopy in elderly patients.

Aims & Methods: To assess comparative effectiveness in elderly patients, we conducted a randomized controlled trial with head-to-head comparison of these two methods. We did not enroll the following cases in this study: (1) patients received endoscopy for treatment, (2) patients were diagnosed with ileus, (3) patients wished to use a sedative agent before colonoscopy. A total of 447 patients in two centers were randomized to either water exchange (WE) or the standard air (CO₂) insufflation technique (AI). In WE, warm water was infused through the forceps channel of the colonoscopy using a foot-switch-controlled water pump. Water used to aid insertion was removed predominantly during the insertion phase. Suspended fecal matter and residual air pockets were removed by suction, followed by infusion of water to improve the view. The primary outcome was patient intraprocedural pain and the secondary outcome was doctor comfort and satisfaction. These outcomes were evaluated using a questionnaire (Score 1 to 5). Clinical trial registry number is UMIN000009706. All authors declare that there are no conflicts of interest.

Results: Forty four patients were excluded for further analysis. As a result, 403 patients without sedation were analyzed. The number of elderly patients aged 75 years and over was 83 (20.6%). There were no differences in patient age (65.6 ± 12.0 vs. 63.1 ± 12.6 years) and body mass index (22.9 ± 3.8 vs 23.3 ± 4.2 kg/m²) between WE and AI groups. Patients in WE group reported less intraprocedural pain than those in AI group (2.18 ± 1.15 vs. 2.42 ± 1.03; unpaired t-test, p = 0.024). In contrast, there was no statistically significant difference in elderly patients between WE and AI groups (2.10 ± 1.12 vs.2.21 ± 0.98). Colonoscopy by trainee colonoscopists (T group) who performed less than 500 colonoscopy was more painful than that by non-trainee (NT group) (2.44 ± 1.08 vs.1.59 ± 0.78; p < 0.01). In T group, there was no significant difference in pain during colonoscopy in elderly patients between WE and AI groups (2.18 ± 1.15 vs. 2.45 ± 1.11). On the contrary, in NT group, WE could reduce pain in elderly patients compared to AI (1.88 ± 1.04 vs. 2.25 ± 1.06; p = 0.033).

Conclusion: Although WE is superior to AI in attenuating real-time insertion pain during colonoscopy, the efficacy of WE is limited in elderly patients. Unlike trainees, colonoscopy experts can attenuate insertion pain of elderly patients by utilizing WE technique.

Disclosure of Interest: None declared

P0792 OPTICAL DIAGNOSIS OF T1 COLORECTAL CARCINOMA BY COLONOSCOPY EXPERTS, GENERAL GASTROENTEROLOGISTS AND GI-FELLOWS: IS IT FEASIBLE?

M. Van Der Vlugt¹, S. van Doorn¹, B. Bastiaansen¹, P. Fockens¹, E. Dekker¹

¹Department of Gastroenterology and Hepatology, Academic Medical Center Amsterdam, Amsterdam, Netherlands

Contact E-mail Address: m.vandervlugt@amc.uva.nl

Introduction: An increasing number of T1 colorectal cancers are diagnosed. It is important to endoscopically recognize these cancers correctly to establish an optimal treatment strategy. Asian studies show that colonoscopy experts can reliably recognize early cancers. In daily practice however, accurate optical diagnosis of T1 carcinomas still seems challenging.

Aims & Methods: To evaluate the performance of optical diagnosis of T1 cancers by colonoscopy experts, general gastroenterologists and GI-fellows. We selected good quality endoscopic images (white light and NBI images) without magnification of 43 lesions: 19 T1 carcinomas and 24 benign polyps (7 sessile serrated adenomas and 17 adenomas with low-grade dysplasia) ranging from 8-30 mm in size. Seven international colonoscopy experts, 7 general gastroenterologists and 14 GI-fellows assessed all images for an optical diagnosis and level of confidence (high/low). We calculated sensitivity, specificity, negative and positive predictive value (NPV,PPV) for optical diagnosis of T1 carcinomas using 2x2 tables. For fellows, this was also described according to years of training.

Results: Sensitivity was 60% for all endoscopists. Sensitivity was best for experts (67%) compared to general gastroenterologists and fellows (53% and 59% resp.). NPV was lowest for general gastroenterologists. Of all endoscopists, only two (1 expert and 1 fellow) reached a NPV of ≥ 90%. 645 (54%) optical diagnoses were made with high confidence. High confidence diagnoses correlated with higher overall sensitivity, specificity, PPV and NPV, especially for fellows.

Abstract number: P0792 Table 1.

Optical diagnosis according to level of experience and level of confidence for diagnosis.

	No. of high confidence predictions (% of total)	Sensitivity, %(range)	Specificity, %(range)	Positive predictive value, %(range)	Negative predictive value, %(range)
All endoscopists (n=28) Experts (n=7) General gastroenterologists (n=7) Fellows (n=14) -1st year training (n=2) -2nd year training (n=3) -3th year training (n=3) -4th year training (n=6)		60 (26-90) 67 (42-90) 53 (32-74) 59 (26-90) 37 (26-47) 58 (42-68) 60 (47-74) 67 (42-90)	95 (79-100) 95 (79-100) 96 (83-100) 95 (88-100) 94 (92-96) 93 (88-100) 93 (88-100) 97 (92-100)	91 (72-100) 92 (72-100) 91 (78-100) 90 (73-100) 82 (82-83) 87 (73-100) 87 (75-100) 94 (82-100)	75 (62-92) 78 (67-92) 72 (64-80) 75 (62-92) 65 (62-69) 74 (66-79) 74 (68-81) 79 (69-92)
HIGH CONFIDENCE ONLY
All endoscopists (n=28) Experts (n=7) General gastroenterologists (n=7) Fellows (n=14) -1st year training (n=2) -2nd year training (n=3) -3th year training (n=3) -4th year training (n=6)	645 (54) 229 (76) 143 (48) 273 (45) 20 (23) 33 (26) 76 (59) 144 (56)	65 (0-100) 66 (38-92) 58 (38-100) 68 (0-100) 40 (0-100) 92 (86-100) 63 (40-75) 69 (33-100)	98 (80-100) 99 (94-100) 99 (94-100) 98 (80-100) 100 (100) 100 (100) 98 (93-100) 98 (80-100)	97 (94-100) 97 (90-100) 97 (86-100) 96 (67-100) 100 (100) 100 (100) 94 (86-100) 95 (67-100)	80 (50-100) 80 (68-95) 77 (67-100) 82 (50-100) 63 (50-100) 95 (92-100) 83 (78-86) 82 (66-100)

Conclusion: Sensitivity for predicting a T1 carcinoma and NPV for excluding a T1 cancer was insufficient. Experts did best with sensitivity of 67% and NPV 78%, and the performance of fellows in their last year of training is comparable to that of experts. This indicates that training for optical diagnosis for malignant polyps is needed.

Disclosure of Interest: None declared

P0793 RESECTION OF LARGE COLONIC PEDUNCULATED POLYPS (PARIS IP)

M. A. Alburquerque¹², A. Smarrelli¹, L. Vidal¹, C. Ledezma¹, J. Chevarría³, A. L. Vargas², M. Figa², F. Gonzalez-Huix²

¹Gastroenterology, Hospital de Palamós, ²Gastroenterology, Clínica Girona, ³Nephrology, Hospital de Palamós, Girona, Spain

Contact E-mail Address: nictalope7@gmail.com

Introduction: There are some techniques to resect large colonic pedunculated polyps.

Aims & Methods: To compare the safety of the techniques commonly used to resect large colonic pedunculated polyps ≥ 20mm according to the stalk measures. Descriptive - prospective study (2010-2014) regarding the safety of the techniques to resect large colonic pedunculated polyps, usually used by four endoscopists. We registered: location and polyp features, resection techniques and complications. The polyps were classified in 4 groups according to the stalk measures. The immediate postpolypectomy bleeding (IPPB) was defined as the bleeding during the resection procedure in which was necessary an additional haemostatic technique. Resection techniques: A) Hot snare, B) Adrenaline (0,005-0,01%) injection in the stalk, cutting snare and close of the wound/remnant stalk with clips and, C) Clip (Quick Clip® Olympus and Resolution clip® Boston Scientific) or detachable snare placement (Endoloop MAJ-339 Olympus®) and cutting snare.

Results: There were resected 180 pedunculated polyps ≥ 20mm (Longest diameter=25.34 ± 6.54; 20–60mm) among 168 patients, women: 49(29.16%). Age: 63.53 ± 10.96 y. There were excluded 20 polyps by incomplete data. In the Group 1 (n=38, stalk: Length < 15mm/Diameter ≤ 10mm) were resected with hot snare: 57.89%, while in the Group 2 (n=28, Length ≥ 15mm/Diameter ≤ 10mm) with clip: 57.15%. In the Group 3 (n=30, Length < 15mm/Diameter > 10mm) were resected with Adrenaline injection: 93.33% and in the Group 4 (n=64, Length ≥ 15mm/Diameter > 10mm) with Endoloop®: 75%; p=0.001. The IPPB was the most frequent global complication: 31.10%(56/180), highest in the Group 3: 63.3%, p=0.001; and was resolved with clips with an effectiveness =91.10%(41/45). In the Groups 1 & 2 (stalk diameter ≤ 10mm), the IPPB rate was 18.75%(6/32) in the resected polyps with only snare vs. 31.8%(7/22) in those with clip, p=0.270. In the Groups 3 & 4 (stalk diameter > 10mm), the IPPB rate was higher in the resection with adrenaline injection than Endoloop®: 64.70%(22/34) vs. 10.20%(5/49), p=0.001. In these groups the IPPB rate was not different between clips and adrenaline injection: 50%(3/6) vs. 64.7%(22/34), p=0.65. In the polyps with stalk diameter > 10mm, in the multivariate analysis, the adrenaline injection was significantly associated to IPPB: p=0.0001; OR=15.23(IC95% 4.43–52.34). In the Group 4, the IPPB was higher with clips than with Endoloop®: 50%(3/6) vs. 10.4%(5/48), p=0.036.

Conclusion: In large colonic pedunculated polyps ≥ 20mm with thinner stalk ≤ 10mm the resection with hot snare was acceptably safe. In thicker stalk > 10mm, the polypectomy with Endoloop® was significantly safer when the stalk length was enough to place it; and the adrenaline injection has shown a high risk to IPPB. Some clips type might not have been superior to prevent the IPPB although they are effective to resolve it.

Disclosure of Interest: None declared

P0794 IN VIVO DETECTION OF EARLY COLORECTAL CANCER BY FLUORESCENCE ENDOSCOPY TARGETING THE ENDOTHELIN-A-RECEPTOR

M. M. Mücke¹, D. Bettenworth¹, C. Geyer², K. Schwegmann³, C. Poremba⁴, M. Schäfers³, D. Domagk⁵, C. Höltke², P. Lenz¹⁶

¹Department of Medicine B, ²Department of Clinical Radiology, ³European Institute for Molecular Imaging, University of Muenster, Muenster, ⁴Institute of Pathology Munich-North, Munich, ⁵ Josephs-Hospital, Warendorf, ⁶Department of Palliative Care, University of Muenster, Muenster, Germany

Contact E-mail Address: lenzph@uni-muenster.de

Introduction: Patients suffering from ulcerative colitis are at an increased risk of developing colorectal cancer. Current guidelines recommend surveillance colonoscopy with chromoendoscopy or random biopsies to further improve detection rates of dyplastic lesions. ET-A receptor (ET_AR) expression is known to be significantly increased in various malignancies including colorectal cancer (1). The objective of this study was to evaluate ET_AR-guided fluorescence endoscopy (FE) in vivo and fluorescence reflectance imaging (FRI) ex vivo for detection and characterization of early dysplastic lesions in mice.

Aims & Methods: Colorectal cancer was induced in C57Bl/6 WT mice (n=15) by single injection of azoxymethane (AOM) i.p. and cyclic administration of dextran sodiumsulfate (DSS) in drinking water. A Cy5.5-labeled nonpeptidic ET_AR imaging probe was intravenously injected 24 hrs before endoscopic examination. Tumor development was assessed in vivo by white light endoscopy and FE. Then colons were explanted and examined by fluorescence reflectance imaging using an MS-FX PRO optical imaging system to measure tracer uptake ex vivo. At the end of the experiment tumors were graded after HE staining and evaluated by an expert pathologist. Tumor biology was assessed utilizing the proliferation marker Ki-67 and ET_AR expression was visualized by immunohistochemistry and western blot analysis. Additionally, binding specificity of the tracer was evaluated by simultaneous injection of an equimolar amount of an unspecific fluorochrome (Cy3.5-glycin) and the specific ET_AR tracer.

Results: In 15 mice, 77 adenomas were confirmed up to high-grade dysplasia in standard histology. FE was able to detect ET_AR expression easily applying the fluorescent ET_AR imaging probe. A significant higher fluorescent contrast was observed in colonic adenomas as compared to adjacent non-malignant mucosa (63.4 ± 7.9 vs. 56.6 ± 7.0; P < 0.001). Correspondingly, ex vivo conventional molecular imaging showed significantly increased tracer uptake in colorectal adenoma as compared to healthy mucosa (1211.0 ± 557.4 vs. 509.7 ± 137.0; P < 0.001). Immunochemistry revealed an increased Ki67 and ET_AR expression in colonic dysplasia. Moreover, western blot analysis verified the detected ET_AR expression. No significant difference in tracer uptake between low and high-grade adenoma was found (tumor-to-background ratio: 2.3 ± 0.8 vs. 2.4 ± 0.7, P = 0.589). The tumor-to-background ratio of lesions imaged for Cy3.5 was significantly reduced as compared to Cy5.5 indicating the high binding-specificity of the utilized ET_AR tracer (1.4 ± 0.3 vs. 2.5 ± 0.7, P < 0.001).

Conclusion: In murine colorectal dysplasia ET_AR expression was significantly increased as compared to healthy mucosa. By detection of ET_AR via FE in live mice, a prognostic biomarker for colorectal cancer development is directly visualized during colonoscopy, thus facilitating in vivo tumor characterization on a molecular level.

Disclosure of Interest: None declared

P0795 SHOULD POLYP RESECTION BE PRIORITIZED ACCORDING TO LOCATION?

M. J. Silva¹, R. V. Loureiro¹, P. Russo¹, C. Bernardes¹, V. P. Borges¹, T. Capela¹, M. N. Costa¹, D. Carvalho¹, A. David Marques¹

¹Central Lisbon Hospital Center, Lisboa, Portugal

Introduction: Prediction of histology of colon polyps according to location and other macroscopic features is particularly relevant as colonographic techniques are becoming more widespread. Advanced polyps are smaller in the right colon¹ and right-sided lesions carry increased risk of recurrence of advanced adenomas.² Nevertheless, differences in histologies between right- vs left-sided colon polyps are not well characterized.² When available, such information may be used for prioritizing colonoscopies recommended after colonography (ie, when at least one polyp ≥6mm is observed).³

Aims & Methods: We aimed at characterizing colonic polyp histology according to patient and polyp macroscopic characteristics.

We reviewed all polyps observed in colonoscopies performed during 2013 in an Gastroenterology Department, whose location and histology (from biopsy or complete removal) are unequivocally known. We considered high risk traditional adenomas all those with ≥10mm at colonoscopy or with advanced histology (villous histology or high grade dysplasia).

We reviewed all polyps observed in colonoscopies performed during 2013 in an Gastroenterology Department, whose location and histology (from biopsy or complete removal) are unequivocally known. We considered high risk traditional adenomas all those with ≥10mm at colonoscopy or with advanced histology (villous histology or high grade dysplasia). Patient demographics, as well as polyp macroscopic and microscopic features, were analyzed with STATA® 12.1.

Results: In total, 1960 polyps were analyzed.In the rectum, the most frequent polyps were hyperplastic (53.3%; 218/409); while in the other segments the most common polyp type was tubular adenoma with low grade dysplasia: 48.3% (236/489) in sigmoid colon, 64.5% (158/245) in descending colon, 68.3% (293/429) in transverse colon, 70.6% (202/286) in ascending colon and 69.6% (71/102) in cecum.High risk traditional adenomas were more common in the sigmoid colon (33.5% of polyps; 164/489) and descending colon (26.9%; 66/245) than in other segments.Among polyps ≥6mm (N=878), advanced histology in traditional adenoma was more prevalent in rectal polyps (33.3%; 42/126), followed by polyps in the sigmoid colon (23.8%; 62/260), descending colon (19.7%; 27/137), cecum (18.9%; 7/37), transverse colon (15.2%; 31/204) and ascending colon (14.0%; 16/114). Advanced histology was significant more frequent in distal compared to proximal polyps, both when comparing all polyps (11.9% vs 7.2%, p=0.001) or only those ≥6mm (25.0% vs 15.2%, p < 0.001).

Conclusion: In this series, distal polyps carried a higher risk of advanced histology. Priorization for colonoscopic removal may consider polyp location.

Disclosure of Interest: None declared

P0796 EFFICACY, ACCEPTABILITY, TOLERABILITY AND SAFETY OF LOW-VOLUME POLYETHYLENE GLYCOL SOLUTION PLUS ASCORBIC ACID VERSUS STANDARD POLYETHYLENE GLYCOL SOLUTION IN BOWEL PREPARATION FOR COLONOSCOPY

M. Tajika¹, T. Tanaka¹, M. Ishihara¹, N. Mizuno², K. Hara², S. Hijioka², H. Imaoka², N. Hieda², N. Okuno², T. Yoshida², Y. Yatabe³, K. Yamao², Y. Niwa¹

¹Endoscopy, ²Gastroenterology, ³Pathology and Molecular Diagnosis, Aichi Cancer Center Hospital, Nagoya, Japan

Contact E-mail Address: mtajika@aichi-cc.jp

Introduction: According to an ageing population, and increasing burden of colorectal cancer at an advanced age, colonoscopies are increasingly needed in the elderly. Polyethylene glycol electrolyte lavage solution containing ascorbic acid (PEG-ASC) has recently become available in Japan, as a low-volume lavage solution. However, in view of concerns of hypertonicity for PEG-ASC, we compared it to standard PEG electrolyte solution (PEG-ELS) and evaluated the hematological and biochemical change before and after taking PEG solution.

Aims & Methods: The aim of this study is to compare the efficacy, acceptability, tolerability, and safety of PEG + ASC and standard PEG-ELS, not only in the general population, but also in patients of advanced age. This was a single-blinded, non-inferiority, randomized, controlled trial including adult inpatients. Although 3–4 L of PEG-ELS is used in Western countries, approximately 2 L of PEG-ELS, along with a laxative, is usually considered adequate for bowel preparation in Japan. Subjects were randomized to receive 1.5 L PEG-ASC or 2 L PEG-ELS, and completed a questionnaire on the acceptability and tolerability of the bowel preparation process. Hematological and biochemical parameters were assessed at baseline, 3 hours, and 7 hours after beginning the preparation solution. The Boston Bowel Preparation Scale was used to evaluate bowel cleansing, and a 3-point scale was used to assess mucosal visibility.

Results: One hundred patients were randomized to either the 1.5-L PEG-ASC group (n=50, males 66%, mean age 66.4 years) or the 2-L PEG-ELS group (n=50, males 64%, mean age 67.9 years). Patients in 1.5-L PEG-ASC group were more willing to repeat the procedure than the 2-L PEG-ELS group (72% 1.5-L PEG-ASC group vs. 52% 2-L PEG-ELS group (95% lower confidence limit, for a difference of 1.4%)). No significant differences were found in bowel cleansing (P=0.889) or mucosal visibility (P=0.063) between the groups. Except for sodium bicarbonate in the 1.5-L PEG-ASC group, all hematological and biochemical parameter variations were within the normal range. However, we demonstrated significant statistical changes in the hematological and biochemical parameters such as sodium, chloride, albumin, hematocrit, and acid-base balance parameters after both type of preparation, regardless of patient age, which were not clinically significant.

Conclusion: The 1.5-L PEG-ASC regimen had higher patient acceptability than the 2-L PEG-ELS regimen. Tolerability, bowel cleansing, and safety were similar between regimens. No significant differences in the safety profile were found between subjects aged less than 70 years and those aged 70 years or more; nevertheless, regardless of age, proper hydration is needed throughout the bowel preparation process.

Disclosure of Interest: None declared

P0797 CLINICAL IMPACT OF NEAR-FOCUS NARROW BAND IMAGING IN DIFFERENTIATING NEOPLASTIC AND NON-NEOPLASTIC COLORECTAL SMALL POLYPS FOR TRAINEES

M. Yamada¹², A. Parra-Blanco¹³, M. A´lvarez-Lobos¹, A. Arias-Ernst¹, R. Mansilla¹, A. Espino¹, R. GonzÁlez¹, T. Sakamoto², T. Nakajima², T. Matsuda², Y. Saito², M. Arrese¹

¹Gastroenterology, Pontificia Universidad Católica, Santiago, Chile, ²Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan, ³Gastroenterology, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom

Contact E-mail Address: masyamad@ncc.go.jp

Introduction: Neoplastic colorectal polyps are precursor lesions recommended to remove. Both Narrow band imaging (NBI) and optical magnification have contributed to an accurate endoscopic diagnosis of the colorectal tumors. Recently, a simplified 45 times optical magnification (near-focus NBI) that is activated by only a switch has become commercially available. This near-focus NBI might help trainees to differentiate between neoplastic and non-neoplastic polyps.

Aims & Methods: The aim of this retrospective image evaluation study is to elucidate diagnostic accuracy of near-focus NBI for differential diagnosis of colorectal small polyp in trainees using western setting.

In the pre-study, education according to NICE classification was performed to 7 reviewers [6 trainees and 1 experienced endoscopists (control)] using 15 typical polyps. In Study 1, endoscopic images obtained by high-resolution white-light (WLI), NBI and near-focus NBI of 20 consecutive polyps removed between July and August 2014, were systematically assessed by the 7 reviewers. In study 2, two weeks after the study, endoscopic images of other consecutive 40 polyps removed between August and September 2014, were evaluated by the 7 reviewers after repeating the same lecture and verifying the pathological diagnosis of the 20 polyps in study 1. Diagnostic accuracy and rate of high confidence were analyzed. Trainees had performed <100 colonoscopies and <3 years’ experience. All reviewers were blinded to clinicopathological data and evaluated the images in a random order. All images used in the study 1 and 2 were obtained by Exera III system (Olympus). All polyps were smaller than 10mm.

Results: Before the education, diagnostic accuracy for differentiating adenomas from hyperplastic polyps (HPs) of the trainees and rate of high confidence were 78% (47∼87) and 67% (60∼80).

Study 1) Overall diagnostic accuracy of WLI, NBI, and near-focus NBI for differentiating adenomas from HPs in trainees were 61% (55∼65), 75% (65∼85) and 80% (75∼90), respectively. Overall rate of high confidence in WLI, NBI and near-focus NBI were 73% (35∼90), 65% (45∼95) and 68% (60∼80). In the experienced endoscopist, diagnostic accuracies were high as 65%, 75% and 85%, and high confidence rate was 85%, 95% and 95%, respectively.

Study 2) Overall diagnostic accuracy of WLI, NBI, and near-focus NBI for differentiating adenomas from HPs in trainees were 50% (40∼63), 65% (48∼78) and 71% (53∼83), respectively. Overall rate of high confidence in WLI, NBI and near-focus NBI were 68% (23∼90), 80% (68∼88) and 80% (60∼80). In the experienced endoscopist, diagnostic accuracies were low as 45%, 45% and 60%, and high confidence rate was 83%, 88% and 88%, respectively.

Table: Diagnostic accuracies of the trainees.

	WLI (%)	NBI (%)	Near-focus NBI (%)
Study 1	61 (55∼65)	75 (65∼85)	80 (75∼90)
Study 2	50 (40∼63)	65 (48∼78)	71 (58∼83)

Conclusion: The present study clearly demonstrated that near-focus NBI was superior to WLI and NBI in differentiating neoplastic and non-neoplastic small lesions for the trainees. Near-focus NBI may help trainees to precisely manage colorectal polyps.

Disclosure of Interest: None declared

P0798 COLORECTAL ENDOSCOPIC SUBMUCOSAL DISSECTION AS A RESCUE ENDOSCOPIC TREATMENT AFTER PREVIOUS INCOMPLETE ENDOSCOPIC MUCOSAL RESECTION: A SINGLE-CENTRE EXPERIENCE

M. Majerović¹, H. Iveković¹, B. Bilić¹, P. Markoš¹, N. Rustemović¹

¹Division of Gastroenterology and Hepatology, University Hospital Centre Zagreb, Zagreb, Croatia

Contact E-mail Address: matea.majerovic@gmail.com

Introduction: Indications for colorectal endoscopic submucosal dissection (CR-ESD) include treatment of mucosal tumors with submucosal fibrosis i.e. after previous biopsy or after incomplete endoscopic mucosal resection, EMR. Little is known on the clinical outcomes of this procedure in a western setting.

Aims & Methods: The aim of our study was to evaluate feasibility of CR-ESD as a salvage endoscopic treatment for residual colorectal lesions after incomplete EMR. A retrospective study on a prospectively collected database of endoscopic procedures during period 2013-2015 was done. Data regarding lesion location, the ESD accessories used, procedure time, pathology, margin involvement (R0) and post-procedure complications, were collected.

Results: We identified 9 patients (6 male, 3 female, median age 71 years, range 39-79 years) with this clinical scenario. 8 lessions were located in rectum and 1 in sygmoid colon (median size 25 mm, range 15-80 mm). Lesions included residual adenomas (Paris Is, 7/9pts; Paris Is + IIc, 1/9 pts) and LST-NG (Paris Is + IIa, 1/9 pts). All procedures were done with Dual and Hook knife. Median procedure time was 240 min (range 60-600 min). Pathohistology specimens were: tubular adenoma with low-grade dysplasia (7/9) and villotubular adenoma with high-grade dysplasia (2/9). R0 resection was confirmed in 7/9 pts (78%). Endoscopic treatment of the intraoperative events included closure of perforation (2/9), and hemostasis (3/9). Two-step procedure was needed in 3 patients to complete the resection and post-procedural fever was observed in one patient. During median follow-up of 7 months (range 1-17 months) no delayed complications were observed.

Conclusion: CR-ESD after incomplete EMR is technically demanding and time-consuming procedure. However, in the hands of experienced endoscopist, it is a ‘surgeon sparing’ procedure that can achieve an acceptable rate of R0.

Disclosure of Interest: None declared

P0799 RANDOMIZED COMPARATIVE EVALUATION OF AN ESD SELF-LEARNING SOFTWARE IN FRANCE AND JAPAN

M. Pioche¹, J. Rivory¹, T. Nishizawa², T. Uraoka², I. Lienhart³, T. Ponchon⁴, N. Yahagi²

¹Gastroenterology and endoscopy, Pavillon L, Edouard Herriot hospital, Lyon, France, ²ENdoscopy division, Keio university, Tokyo, Japan, ³Gastroenterology and endoscopy, Edouard Herriot Hospital, ⁴Gastroenterology and endoscopy division, Pavillon L, Edouard Herriot Hospital, Lyon, France

Contact E-mail Address: mathieu.pioche@chu-lyon.fr

Introduction: Endoscopic submucosal dissection is the reference method to achieve en bloc resections for large lesions of the digestive tract. Nevertheless, it is a difficult and risky technique with a long learning curve. To reduce first procedures morbidity, animal models like bovine colon were developed to teach the initial skills. Self-teaching program could be helpful in the western world but also in Asia even if the technique is more spread out. A self-learning software to assist students in the first steps of ESD has been developed by N. Yahagi jointly with Olympus®. We designed this study to evaluate the impact of such a tool on ESD learning curve using a bovine colon model developed previously(1).

Aims & Methods: A prospective randomized comparative study enrolled 37 students (29 in France and 8 in Japan) experienced in interventional endoscopy but not in ESD. Each student was randomized in one of the two groups and performed 30 ESD for a 30 mm simulated rectal lesion in retroflexed position. Group A used the self-learning software whereas group B only observed an ESD procedure movie. No other technical explanation was given to both groups. Procedure duration, resection completeness, perforation rate and the specimen size and surface were assessed. If the procedure exceeded 75 min, the trainee had to stop and we considered it as a failure.

Results: 39 students performed 1170 ESD (group A: 19 students, 570 ESD) (group B: 20 students, 600 ESD) with 57 failures (time out over 75 min) (group A : 26, 4.6%, group B: 31, 5.2%, p=0.26). Among the 1113 resection of a specimen in less than 75 min, the complete resection rate was 76.2% in group A versus 67.4% in group B (p=0.001). The rate of success defined by a complete procedure in less than 75 min without perforation was significantly superior with respectively 70.9% and 61.2% in group A and B (p < 0.001). The perforation rate and the procedure duration were not different with 6.0 vs 6.4 % (p=0.796) and 35.7 vs 34.9 min (p=0.391) respectively. Regarding only the 30^th procedure of each student, the rate of complete resection was superior in group A with 84.2 versus 70% (p=0.292). Other analyses (learning curve, french vs japanese trainees) are ongoing.

Conclusion: The use of an ESD self-learning software is effective to improve the quality of resection compared to a standard teaching with procedure movies. The main advantage is to save some supervision time. This result suggests to incorporate such a self-learning software in the ESD teaching program.

Disclosure of Interest: None declared

P0800 SKIPPING ONE PRODUCT GENERATION OF COLONOSCOPES RESULTS IN DIFFERENCES IN POLYP MISS RATES: RESULTS FROM A PROSPECTIVE RANDOMIZED TANDEM STUDY

M. Pioche¹, K. Zimmermann-Fraedrich², G. Andrisani³, C. Gerges⁴, I. Lienhart¹, E. Dekker⁵, V. Weingart⁶, T. Noder², L. Petruzziello³, J. Kandler⁴, J. Wallner⁶, A. Denis⁷, P. Fockens⁵, G. Costamagna³, H. Neuhaus⁴, S. Touzet⁷, T. Ponchon¹, T. Rosch², H.-D. Allescher⁶

¹Hopital Edouard Herriot, Lyon, France, ²Universitatskinikum Hamburg-Eppendorf, Hamburg, Germany, ³Policlinico Gemelli, Roma, Italy, ⁴Evangelisches Krankenhaus, Dusseldorf, Germany, ⁵Academic Medical Center, Amsterdam, Netherlands, ⁶Klinikum Garmisch-Partenkirchen, Garmisch-Partenkirchen, Germany, ⁷Pole IMER, Lyon, France

Contact E-mail Address: thierry.ponchon@chu-lyon.fr

Introduction: Multiple randomized studies have shown that changing certain features in imaging of colonoscopes (structure enhancement, wide angle view, HDTV) do not consistently improve adenoma detection rate. Similarly, change from one endoscope generation to the next one, implementing one or even several new features were not successful in achieving a rise in ADR either. There is however indirect evidence that it might need to skip one colonoscope generation (i.e. change from one generation to the next but one) may have this effect.

Aims & Methods: We therefore compared the latest generation Olympus colonoscopes (Exera III, CF- or PCF-190) with the next to last one (CF- or PCF 165) in a prospective randomized multicenter tandem study. Patients with increased risk for colorectal neoplasia (FOBT positive, personal or familial history of colorectal cancer or adenoma, rectal bleeding, recent change in frequency and consistency of stools) were included. Primary outcome was the adenoma miss rate with 190 colonoscopy in comparison to 165 colonoscopy.

Results: 848 patients (48% male, mean age 58.3 years, range 19-87) with personal (41%) or familial (38%) history of colorectal neoplasia, rectal bleeding (19%) and other indications were included. A total of 304 missed adenomas were found in 197 patients. Of the 425 patients in the intervention group (PC or PCF 190 first), 68 patients (16.0%; 95% CI: 12.5 % - 19.5%) had at least one adenoma missing during the 1st procedure, as compared with 129 of the 423 (30.5%; 95% CI: 26.1% - 34.9%) patients in the control group (PC or PCF 165 first). This difference was significantly different between the 2 study groups (p < 10-3). Adenoma detection rate (percentage of patients with at least one adenoma) during the first colonoscopy was 43.3% (184/425) in the intervention group (190 series) and 36.6% in the control group (165 series) (p < 0.05).

Conclusion: Also based on negative results of previous trials, this randomized tandem study shows that it may take two instrument generation improvements before an increase of adenoma miss rate can be observed.

Disclosure of Interest: None declared

P0801 NEW ISOLATED BOVINE COLON MODEL DEDICATED TO COLONIC ESD HANDS-ON TRAINING: DEFINITION AND PRELIMINARY EVALUATION

M. Pioche¹², J. Rivory¹, G. Aguero-Garcete³, O. Guillaud⁴, C. Lafon², T. Uraoka⁵, N. Yahagi⁵, T. Ponchon⁴

¹Gastroenterology and endoscopy, Pavillon L, Edouard Herriot hospital, ²U1032, INSERM, ³Gastroenterology and endoscopy division, Pavillon L, Edouard Herriot Hospital, ⁴Gastroenterology and endoscopy division, Pavillon L, Hôpital Edouard Herriot, Lyon, France, ⁵Endoscopy division, Keio university, Tokyo, Japan

Contact E-mail Address: mathieu.pioche@chu-lyon.fr

Introduction: Endoscopic submucosal dissection is the reference method to achieve en bloc resections for large lesions of the digestive tract. Nevertheless, it is a difficult technique with long learning curve and relatively high risk of perforation. To reduce the risk of first procedures, animal models have been developed to teach the initial skills. In Japan, stomach ESD is the first step for students and pig stomach is a dedicated model to learn ESD in gastric conditions. In Europe, since the number of gastric lesions is low compared to colonic ones, we have to develop different strategies of teaching with dedicated models. Pig colon is a good model but thinner and more difficult than human and the caliber of the bowel is sometimes too narrow to work in retroflexed position. In this present work, we evaluated a bovine colon model to perform rectal ESD in retroflexed position.

Aims & Methods: In a first step we prepared 6 bowels to perform ESD using Dual Knife® and Nestis Enki II® in order to precise the preparation protocol. Using this protocol, two endoscopists unexperienced in ESD performed 62 procedures of 30 mm on 8 colon models. In parallel, we compared the ellipse formula evaluation of specimen area with measured area using a picture size software.

Results: A precise protocol to defrost and to prepare the colon was defined. The lesions were marked with a plastic circle of 28 mm diameter after inversion and swallowing of the bowel. The two students achieved complete en bloc resection in 89.1% of cases with 6.2% of perforations. A large heterogeneity appeared between the speed and the success rate depending on the age of the animal bowel. Using veal colon (animal under 8 months), the rate of failure was significantly higher (p=0.002) and the speed of dissection was significantly lower (p < 0.001) than using adult bovine colon (aged between 12 and 24 months). The progression of dissection speed was significant between the first and the second half of the cases with respectively 0.49 and 0.59 cm²/min using only the cases on adult bovine colon. No significant difference appeared between measured and calculated areas of the specimen.

Conclusion: Bovine colon model is a suitable model to teach ESD in the rectum. Nevertheless, adult bovine colon model is more homogeneous than veal ones and has to be used for comparative works. Calculated area using ellipse formula is a good way to evaluate the size of the specimen with no difference with measured areas using picture measurement software.

Disclosure of Interest: None declared

P0802 ENDOSCOPIC DIAGNOSIS OF COLORECTAL POLYPS USING BLUE LASER IMAGING AND MAGNIFICATION: IMPACT OF A SHORT TEACHING PROGRAM

M. Barret¹, D. T. Cao¹, S. Grabar², M. Camus¹, S. Leblanc¹, J. Dreanic¹, M. Dhooge¹, R. Coriat¹, F. Prat¹, S. Chaussade¹

¹Gastroenterology, ²Epidemiology and Biostatistics, Cochin Hospital, Paris, France

Introduction: Blue Laser Imaging (BLI) is a new image-enhanced endoscopy technique, proven highly effective, in addition to magnification endoscopy, to differentiate between neoplastic and non-neoplastic colorectal polyps. We sought do determine if these results could be reproduced in a group of non expert western endoscopists after a short teaching program.

Aims & Methods: 120 endoscopic images, including white light endoscopic images, standard BLI, BLI-bright and magnified images of 62 small colorectal polyps were used for the study. These pictures were shown to a group of 138 gastroenterologists who were asked to score each polyp as an adenoma or an hyperplastic polyp. After a one hour teaching lesson dedicated to the diagnostic criteria of hyperplastic and adenomatous lesions under BLI or narrow-band imaging and magnification, a posttest was conducted with the same images arranged in a different order.

Results: 61 gastroenterologists, among which 29 residents and 32 seniors, filled the pre and posttest questionnaires. Only 31.7% had previously received a formalized teaching in any kind of virtual chromoendoscopy. The overall sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy of BLI with magnification for the endoscopic diagnostic of small colorectal adenomas were 0.64 (95% CI = 0.63-0.66), 0.58 (95% CI = 0.55-0.6), 0.81, 0.37, and 0.63, respectively. These numbers were not significantly different in residents and senior endoscopists, and did not significantly improve after the teaching lesson. The proportion of diagnostic certainty improved from 31.5% to 41.9% (p < 0.0001) after training.

Conclusion: For non expert Western endoscopists, a one hour teaching lesson is insufficient to acquire basic knowledge in BLI and magnification endoscopy. Longer training programs might be required before such advanced endoscopic imaging techniques can be implemented in France.

Disclosure of Interest: None declared

P0803 EFFECTIVENESS OF A TRAINING SYSTEM FOR THE IDENTIFICATION OF DIMINUTIVE COLORECTAL POLYP HISTOLOGY USING NARROW BAND IMAGING

M. J. A. Oliman¹, E. M. Bondoc¹, I. H. Y. Cua¹, A. Rastogi²

¹Institute of Digestive and Liver Diseases, St. Luke's Medical Center, Quezon City, Philippines, ²Division of Gastroenterology, Veterans Affairs Medical Center, Kansas City, United States

Contact E-mail Address: mjoliman@yahoo.com

Introduction: Patel et al developed a system that effectively trained gastroenterology fellows to identify diminutive colorectal polyp histology using Narrow Band Imaging (NBI).¹ It, however, requires the presence of an expert to provide active feedback during the training session, limiting its applicability. A modified version of the training system was thus developed and tested, which utilised a computer-based testing module, which provided automated feedback on participant performance.

Aims & Methods: A single-center, prospective, educational evaluation study was conducted among 16 gastroenterology consultants and fellows to assess if the modified training system is effective, and if its effects are durable for at least 3 months. Participants initially watched a teaching presentation that described the NBI findings that distinguish polyp histology. They then used a computer-based testing module, operable using a web browser, that showed 80 videos of diminutive colorectal polyps. Predictions of polyp histology and degrees of confidence were recorded. After each video, the module provided feedback by showing a representative picture of the polyp and providing the actual polyp histology and the NBI findings that support the prediction. Performance was evaluated by comparing predicted histology with actual histology. To evaluate durability of learning, after 3 months, the same videos were shown to the participants, and they were again asked to predict polyp histology.

Results: Participant performance and percentage of high-confidence predictions improved significantly as they progressed through video blocks. Predictions made with high confidence were statistically superior to those made with low confidence. All participants performed well during both study sessions, achieving > 90% accuracy, sensitivity, specificity, PPV, and NPV for high confidence predictions. The participants' experience in endoscopy did not affect performance or percentage of high-confidence predictions.

Conclusion: The modified training system effectively trained participants to identify diminutive colorectal polyp histology using NBI. Learning acquired from this system is durable for at least 3 months. This system is noteworthy in its ability to provide automated feedback and its potential to be used online, making it more applicable in a wider spectrum of clinical settings. Further studies that evaluate the long-term durability of learning from this system, as well as the in vivo real-time performance of trained endoscopists are recommended.

Disclosure of Interest: None declared

P0804 THE ADEQUACY OF BOWEL PREPARATION HAS NO IMPACT ON ADENOMA DETECTION RATES

C. D. Mills¹, A. Swaine², C. McCamley³, V. Portelli⁴, M. Swan¹

¹Gastroenterology, ²Medicine, ³General Surgery, Monash Health, ⁴Endoscopy, West Gippsland Healthcare Group, Melbourne, Australia

Contact E-mail Address: chris.mills@monashhealth.org.au

Introduction: Bowel preparation is recognised as an important factor for the completion of colonoscopy. However, due to heterogenous methodologies of published literature, consensus agreement on the effect of bowel preparation on adenoma detection rate is unclear. There has been an unclear impact of the degree of colonic preparation in the literature, in part because of the differences in methodology between studies. The degree of bowel preparation is used as a marker of colonoscopic adequacy, with current guidelines suggesting shorter interval surveillance for those patients with inadequate bowel preparation at index colonoscopy.

Aims & Methods: To compare the polyp and adenoma detection rates of the adequacy of bowel preparation.

A retrospective study was performed from prospectively collected data from three day endoscopy centers involving 4 experienced gastroenterologists. Twelve hundred procedures were identified. Exclusion criteria included a previously performed partial or total colectomy or in the case of multiple endoscopies, having a previous colonoscopy within the study period, or in the case where inadequate description of the degree of colonic preparation was found.

Results: A total of 1122 procedures were analyzed. Participants had an average age of 59.95 years, with 51.4% being female. There was no difference between the two groups in terms of demographics, indication or colonic insufflation method used. Results demonstrated there was no statistically significant difference in the adenoma detection rates dependent on the degree of bowel preparation, even when excellent, good and fair preparation were grouped together for subsequent analysis.

Abstract number: P0804

Parameter		Excellent / Good Bowel Preperation	Fair / Poor / Inadequate Bowel Preperation	OR / t	CI	p
Sex	Male	370	212	1.16	0.92-1.46	0.2
	Female	406	270	0.86	0.68-1.08	0.2
Polyp Detection	PDR	0.322	0.368	0.87	0.69-1.11	0.28
	ADR	0.166	0.191	0.87	0.64-1.20	0.4
Parameter		Excellent / Good / Fair Bowel Preperation	Poor / Inad equate Bowel Preperation	OR / t	CI	p
Sex	Male	500	42	0.79	0.50-1.26	0.33
	Female	540	36	1.26	0.79-2.0	0.33
Polyp Detection	PDR	0.337	0.342	0.98	0.61-1.59	0.94
	ADR	0.178	0.165	1.1	0.6-2.04	0.76

Conclusion: The degree of bowel preparation appears to have little bearing on the adenoma detection rate. This finding supports that the adenoma detection rate is independent of bowel preparation, and other factors affecting bowel preparation should be the subject of further study.

Disclosure of Interest: None declared

P0805 THE COLONOSCOPIC ADENOMA DETECTION RATE INCREASES DEPENDING UPON THE METHOD OF INSUFFLATION

C. D. Mills¹, A. Swaine², C. McCamley³, V. Portelli⁴, M. Swan¹

¹Gastroenterology, ²Medicine, ³General Surgery, Monash Health, ⁴Endoscopy, West Gippsland Healthcare Group, Melbourne, Australia

Contact E-mail Address: chris.mills@monashhealth.org.au

Introduction: There has been an increasing use of carbon dioxide insufflation recently for colonoscopy as this has been shown to improve patient comfort, shorten procedure duration and decrease the use of post procedural analgesia. There have been no studies to date comparing the difference between adenoma detection rates of carbon dioxide or air insufflation.

Aims & Methods: To compare the polyp and adenoma detection rates of carbon dioxide compared to air insufflation for colonoscopy.

A retrospective study was performed from prospectively collected data from three day endoscopy centers involving 4 experienced gastroenterologists. Twelve hundred procedures were identified. Exclusion criteria included a previously performed partial or total colectomy or in the case of multiple endoscopies, having a previous colonoscopy within the study period.

Results: A total of 1163 procedures were analyzed. Participants had an average age of 59.9 years, with 51.4% being female. There was no difference between the two groups in terms of demographics, time of day of the procedure, and indication. Results demonstrated there was a statistically significant difference in the adenoma detection rates between the two groups. The carbon dioxide group had a significant positive advantage in the detection of adenomas. Other procedural parameters were not statistically different.

Parameter		CO2 Group	Air Group	OR / t	CI	p
Sex
	Male	316	245	1.04	0.82-1.31	0.75
	Female	332	267	0.96	0.77-1.22	0.76
Age		60.3	59.5	0.978		0.33
Withdrawl Time		7.47	7.32	0.55		0.58
Bowel Preperation
	Excellent	31	17	1.47	0.80-2.69	0.21
	Good	370	321	0.79	0.62-1.01	0.06
	Fair	180	124	1.21	0.92-1.57	0.17
	Poor	40	22	1.47	0.86-2.50	0.16
	Inadequate	13	4	2.6	0.84-8.03	0.10
Polyp Detection
	PDR	0.36	0.33	1.13	0.84-1.51	0.41
	ADR	0.22	0.16	1.39	1.02-1.89	0.03

Conclusion: Carbon dioxide insufflation was shown to have better adenoma detection rates when compared with air insufflation. This finding further enhances the case for carbon dioxide insufflation in addition to already established procedural benefits.

Disclosure of Interest: None declared

P0806 CLINICOPATHOLOGICAL STUDY OF SERRATED LESIONS OF THE COLORECTUM

M. Sugimura¹, M. Iwabuchi¹, T. Fujiya¹, Y. Abe¹, H. Suzuki², J. Sakurada², K. Ukai¹, K. Tadokoro¹

¹Gastroenterology, ²Pathology, Sendai Medical Center, Sendai, Japan

Contact E-mail Address: msugimura@snh.go.jp

Introduction: Serrated lesions of the colorectum are the precursors of microsatellite unstable carcinomas. However, their clinical and pathologic features are still unclear and need further exploration.

Aims & Methods: The aims of this study was to clarify the clinicopathological features of colorectal serrated lesions. We reviewed clinical charts and pathological files of 3591 endoscopically resected specimens during January 2007 and December 2014 in our hospital. A total of 282 serrated lesions resected were classified into three categories : HP (hyperplastic polyp), SSA/P (sessile serrated adenomas/ polyps), and TSA (traditional serrated adenoma), according to the WHO criteria. We examined the clinical features of these cases. Then we studied the expressions of Ki-67 and MUCs (MUC2, MUC5AC and MUC6) immunohistochemically to evaluate the differences of the distribution of proliferation and the profile of mucins in these serrated lesions.

Results: Of these 282 lesions, a total of 151 (53.6%) were HP, 63 (22.3%) SSA/P, and 68 (24.1%) TSA. Male to female ratio (M/F) was 2.60 for HP, 1.17 for SSA/P, and 2.40 for TSA. Mean size of SSA/Ps (11.3mm) and TSAs (9.5mm) were significantly larger than that of HP (7.9mm). SSA/Ps were located predominantly in the proximal colon, whereas HP and TSA were mainly located in the sigmoid colon and rectum. 85% of SSA/Ps were flat in macroscopic appearance. SSA/Ps and HPs were whitish or almost the same as adjacent mucosa in color, whereas TSAs had a tendency to be reddish. Magnified colonoscopy showed Type II open pit pattern as characteristic of SSA/Ps, whereas pinecone-shaped pit pattern as that of TSAs. Incidences of concomitant carcinomas in HP, SSA/P, and TSA were 0% (0 out of 151), 3.2% (2 out of 63), and 2.9% (2 out of 68), respectively. Ki-67 positive cells in HP showed regular, symmetric distribution, and those in SSA/P did irregular asymmetrical pattern, whereas most of those in TSA were distributed in “ectopic crypts”. Expression levels of MUC2, MUC5AC and MUC6 were significantly different between the serrated lesions ; SSA/Ps and HPs were positive for MUC5AC in comparison with TSAs.

Conclusion: Our studies showed the three types of serrated lesions have their own distinct features and could be helpful to distinguish between them. SSA/P and TSA are premalignant lesions of colorectum and we should detect these lesions and completely remove endoscopically.

Disclosure of Interest: None declared

P0807 FLEXIBLE ENDOSCOPY FOR DIAGNOSIS OF TUBERCULOSIS OF A LARGE BOWEL IN PATIENTS WITH HIV/TB CO-INFECTION

M. Reshetnikov¹, I. Sokolina¹, B. Bormotov¹, M. Synitsyn¹, M. Kalinina¹

¹Moscow Government Health Department, Moscow Research and Clinical Center for Tuberculosis Control, Moscow, Russian Federation

Contact E-mail Address: taxol@bk.ru

Introduction: In patients with HIV/TB co-infection TB-process is characterized by development of generalized and complicated forms with multiple localizations – in lungs, intrathoracic lymph nodes, in inraabdominal, mezenterial lymph nodes, bowel, peritoneum, spleen. Most of the patients of HIV/TB co-infection complain of the abdominal pain, alvine flux, which may be caused by any inflammatory process – both specific or nonspecific, adverse effects of TB-drugs and HIV-therapy. This problem demands attention and diagnostics. Diagnosis of large bowel tuberculosis and inflammatory bowel diseases can be difficult with patients HIV/TB co-infection. Flexible endoscopy and biopsy are necessary for revealing the pathology.

Aims & Methods: Data of 39 patients observed in the surgical department of Moscow Research and Clinical Center for Tuberculosis Control of the Moscow Government Health Department in the period from 2010 to 2014 with the suspecting on TB-process in bowel are examined. 32 (82,1%) patients had lung forms of tuberculosis, 7 (17,9%) patients were hospitalized with the suspecting on TB-process in bowel, these patients had no lung TB. Complex examination of all the patients included ultrasonography of abdominal cavity organs, oesophagogastroduodenoscopy, irrigoscopy, computer tomography of abdominal cavity organs and examination of fecal masses on Mycobacterium tuberculosis by the luminescent microscopy and cultural method. Colonoscopy was performed with biopsy for histological examination, microscopy, cultural method and PCR.

Results: Visual signs of large bowel tuberculosis were observed in 29 (74.4%) of patients. Types of tuberculosis lesions of large bowel are described: military form, infiltrative and infiltrative-ulcerous. They were described as erosion, infiltrative and infiltrative-ulcerous. Epithelioid-cellular granuloma was revealed in the material of biopsy in 19 (48.7%) cases. In 11 (28.2%) cases Mycobacterium tuberculosis was detected. In 2 patients (5,1%) adenocarcinoma of the large bowel was diagnosed, in 3 (7.7%) citomegaloviral ulcerative colitis was observed, in 15 (38.7%) nonspecific colitis was revealed. All the patient were treated with TB drugs, in 22 patients (56.4%) improvements, such as pain and alvine flux elimination were observed, defecation was normalized. 7 patient (17.9%) needed in the correction of TB drug therapy.

Conclusion: To sum up, colonoscopy is a rapid and valuable method of abdominal cavity organs tuberculosis diagnostic.

Disclosure of Interest: None declared

P0808 SYSTEMIC REVIEWS AND META-ANALYSIS: THE EFFECT OF PATIENT EDUCATION ON BOWEL PREPARATION FOR COLONOSCOPY

M.-J. Chen¹, C.-W. Chang¹, C.-H. Chu¹, T.-E. Wang¹, H.-Y. Wang¹, S.-C. Shih¹

¹Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan, Taipei, Taiwan, Province of China

Contact E-mail Address: mingjen.ch@msa.hinet.net

Introduction: Colonoscopy is a useful and widely available tool for diagnosing and managing colorectal diseases. [1] According to the US National Polyp Study, colonoscopy can reduce the incidence and associated mortality of colorectal cancer (CRC) and polypectomy can lower colorectal cancer death rates if polyps are detected during colonoscopy.

Aims & Methods: Effectiveness of bowel preparation is closely linked to patient compliance and the subsequent result of colorectal cancer screening.[2] Poor bowel preparation can result in missed colonic neoplasms, a difficult and time-consuming procedure, and an increased risk of complications. This meta-analysis aimed to determine the effect of educational intervention on the quality of bowel preparation before colonoscopy.

A comprehensive literature review identified randomized controlled trials measuring the effect of educational intervention on the quality of bowel preparation. Two reviewers independently screened relevant articles, extracted data, and assessed the risk of bias. The primary outcome was the quality of each bowel preparation before colonoscopy using a particular assessment scale. The secondary outcomes were polyp detection rates during the procedure and the need for a repeat colonoscopy due to incomplete examination. The quality of all studies was assessed with the 5-point Jadad scale for assessing RCTs. Studies with 3 or more points were considered high quality.

Results: Nine randomized controlled trials were included in this meta-analysis. In all, 2885 patients were enrolled, with 1458 receiving education and 1427 assigned to the control group. Education before colonoscopy can lead adequate bowel preparation. A significant difference was observed in adequate bowel preparation between the education and control groups (OR = 1.97, 95% CI 1.63-2.38). However, no significant differences were identified in polyp detection rates (OR = 1.24, 95% CI 0.79-1.94) and the need for repeat colonoscopy (OR = 0.47, 95% CI 0.21-1.04) between both groups. The subgroup analyses in this meta-analysis based on education delivery methods, use of educational tools, and geographical differences in education delivery indicated that bowel preparation significantly improved after patient education.

Conclusion: Concerning the bowel preparation in all studies the intervention leads to better outcome, the consistency is an important indication to establish the causality. However, there is insufficient evidence to assess improvements in polyp detection rate and avoidance of a repeat colonoscopy.

Disclosure of Interest: None declared

P0809 CLINICAL OUTCOME OF ULCERATIVE COLITIS WITH MUCOSAL HEALING DEMONSTRATED BY WHITE LIGHT ENDOSCOPY BUT WITH SUBTLE ABNORMALITIES DETECTED BY HIGH DEFINITION ISCAN ENDOSCOPY

M. Fort Gasia¹, X. Gui², R. Panaccione¹, G. G. Kaplan¹, S. Ghosh³, M. Iacucci¹

¹IBD unit, University of Calgary, Calgary, AB, ²Department of pathology, ³Department of Medicine, University of Calgary, Calgary, AB, Canada

Contact E-mail Address: iacuccim@yahoo.it

Introduction: Current practice is to assess mucosal inflammation in patients with ulcerative colitis (UC) with white light endoscopy (WLE). However, high definition (HD) iSCAN endoscopy can characterize in details the mucosal and vascular pattern to assess mucosal healing (MH) and inflammation. Subtle endoscopic and histologic abnormalities can still be detected in the apparently healed mucosa and the clinical significance of this is still uncertain

Aims & Methods: We aimed to monitor the clinical outcome of patients with Mayo subscore of 0 and to determine if abnormal mucosal and vascular pattern detected on HD iSCAN endoscopy are associated with worse prognosis of the disease.

79 patients (34 female, median age 48, range 19-72) with quiescent UC Mayo subscore of 0 were followed for a median period of 19 months. All of these patients were previously endoscopically assessed by WLE and HD iSCAN (Pentax EPKi processor (EC-3490Fi; Pentax Tokyo) and Mayo endoscopic subscore was assigned to patients according to WLE findings. Mucosal pattern on iSCAN was graded as 1=normal, 2=mosaic pattern, 3=tubular-gyrus, 4=nodular rosette. The vascular pattern was graded as 1= normal, 2=spiral isolated vessels, 3=crowded tortuous vessels, 4=irregular vessels. The histologic grading system New York Mount Sinai score was used to assess the grading of inflammation on histology. The clinical outcome was assessed by monitoring Mayo clinical score, CRP levels, further endoscopic evaluation, changes in treatment, use of steroids, introduction of new medication, admission to hospital and colectomy rate. Statistical analysis was performed with Chi Square test and compared the endoscopic findings between patients that flared and patients that remained stable.

Results: Eleven patients (13.9%) out of 79 developed a relapse of UC. The initial endoscopic assessment of these eleven patients showed an abnormal mucosal pattern in 2 patients (18.2%) and an abnormal vascular pattern in 7 patients (63.6%). Amongst the 68 patients that remained stable, 35 (51.5%) presented an abnormal vascular pattern and 10 (14.7%) had an abnormal mucosal pattern on HD iSCAN colonoscopy. Histologic assessment showed quiescent colitis in all patients. There was no statistical significance between patients that relapsed and those that remained stable when comparing the distribution of normal and abnormal iSCAN scoring.

Conclusion: A high proportion of patients with mucosal healing presented subtle residual changes detected by HD iSCAN endoscopy. However, this was not associated with increased frequency of relapse or worse outcome of the disease. A more precise endoscopic score is needed to better describe the endoscopic features of mucosal healing in those patients that relapse after initial Mayo endoscopic score of 0.

Disclosure of Interest: None declared

P0810 QUALITY OF COLONOSCOPY IN NATIONAL COLORECTAL CANCER SCREENING PROGRAME IN CROATIA

M. Kalauz¹, N. Antoljak², M. Katicic³, M. Kujundžić⁴, M. Strnad Pešikan⁵, D. Stimac⁶, M. Samija⁷, V. Stamenić⁸, D. Skoko Poljak⁹, Z. Ebling¹⁰, H. Ivekovic¹

¹Clinical Hospital Center Zagreb, ²2.Croatian National Institute of Public Health, Zagreb, Croatia and University Zagreb, Medical School, Zagreb, ³3.University Zagreb, Medical School, Zagreb, Croatia, ⁴4.Gastroenterology, University Hospital Dubrava, Zagreb, Croatia, ⁵2.Croatian National Institute of Public Health, Zagreb, Croatia and University Zagreb, Medical School, Zagreb, Croatia, Zagreb, ⁶Gastroenterology, University Hospital Centre Rijeka, Rijeka, Croatia, Rijeka, ⁷6.University Hospital for Tumors, Zagreb, Croatia, ⁸7.Ministry of Health, Zagreb, Croatia, ⁹valerija.stamenic@miz.hr, Zagreb, ¹⁰Health Centre Osijek, Osijek, Croatia

Contact E-mail Address: mirjanakalauz1@gmail.com

Introduction: The Croatian National Colorectal Cancer Screening Program was established by the Ministry of Health, and started at September 2007.

Aims & Methods: The Croatian National Colorectal Cancer Screening Program was established by the Ministry of Health, and started at September 2007. The aim of this study is to assess the quality of screening colonoscopy based on the fecal occult blood test (FOBT- guaiac Hemognost card-test).From 1.419.639 individuals invited to CRC screening till the end of first cicle, 288.935 (21%) persons returned correctly applied stool specimen on FOBT cards, and among them there were 15.578 (6.3%) positive. Colonoscopies were performed in 10.428 cases (67%), by 62 endoscopists in 24 centers. The quality of colonoscopies were analyzed for sample of 1003 colonoscopies, using caecal intubation rate (CIR), the adenoma and carcinoma detection rate (ADR, CDR), percentage of polypectomy during the first colonoscopy, and quality of colon cleaning. All parameters were assessed for the whole population, and the individual centers.

Results: In this sample, CIR for whole population was 82%, for individual centres 18–100%. We found 1028 polyps in 391 colonoscopied persons (ADR-39%, for centres 0–51%), and 47 cancers (CDR–4,7%). 428 (42%) polyps were immediate removed during the screening colonoscopy (for centres 0–92%). Remaining polyps, mostly larger than 1.5 cm, were scheduled for second colonoscopy. Colon cleaning was satisfactory for good and complete examination in 690 (68%), inadequate in 248 (25%), and very bad in 65 (7%) persons.

Conclusion: Caecal intubation rate was generally satisfactory in most of endoscopic centres. Numbers of polyps and cancers were very high, but proportion of polypectomies during the first screening colonoscopies was rather low. The poor colon preparation and cleansing was the main reason for inadequate examination and should be improved. On the other hand, it is very important to achieve standardized skills of endoscopists, or even, if needed, temporary exclude inadequatelly trained endoscopists from program. It is also required to assure satisfying endoscopic equipment or exclude centres where it is uncomplete or inadequate.

Disclosure of Interest: None declared

P0811 IMPACT OF NEW-GENERATION ENDOSCOPES ON COLONOSCOPY RESULTS

M. Szura¹, A. Pasternak¹, R. Solecki¹, A. Matyja¹, on behalf of Jagiellonian University, Ist. Dept of General, Oncological, G. I. Surgery

¹Ist Dept of General, Oncological and GI Surgery, Jagiellonian University, Krakow, Poland

Contact E-mail Address: msszura@gmail.com

Introduction: Colonoscopy remains the most accurate method for detecting pathologic lesions within large intestine. It can reveal colorectal neoplasm at asymptomatic preinvasive stage allowing for its simultaneous treatment. In recent years the amount and quality of endoscopic examinations have systematically risen. Examination technique and endoscopic equipment have evolved. Electronic video endoscopes offer now a wide field of view with high resolution imaging and electronic colorization of mucosa. Mechanical construction of the endoscope has been redesigned to improve coecal intubation.

Aims & Methods: The aim of this study was to compare colonoscopy results of asymptomatic patients from the same endoscopic center across two date ranges separated by 12 year interval. Retrospective analysis enrolled 3905 colonoscopies performed in one endoscopic center in 2000 – 2001 and 2013 respectively. All examinations were financed by the Ministry of Health as a national screening program for early colorectal cancer detection. Patients aged 40-65 without symptoms suggesting colorectal cancer were included. Analysis concerned frequency of pathological lesions detection, cecal intubation and adenoma detection rates.

Results: Patients were divided into two different groups according to the year in which the colonoscopy was performed. Group I involved 1505 patients examined in 2000-2001 and group II - 2400 examined in 2013. Incidence rate of pathological lesions was 18.4% in group I vs. 30.7% in group II regarding polyps, 20% vs. 24% regarding diverticula, 1% vs. 1.3% regarding hemangiomas and 8% vs. 2.2% for inflammatory lesions, respectively. Colorectal detection rate was 1.2% in both groups. Adenoma detection rate increased from 11.2% in group I to 18.12% in group II.

Conclusion: New-generation endoscopes and physicians who constantly improve their skills contributed to improvement of the detection rate of all polyps, adenomas and diverticula. However, colorectal cancer detection rate still remains the same. The inflammatory lesions incidence was less frequently observed in group II, what undoubtedly results from more restrictive qualification of individuals for screening endoscopy.

Disclosure of Interest: None declared

P0812 COMPARISON AMONG CONVENTIONAL 4L POLYETHYLENE GLYCOL, SODIUM PICOSULFATE AND MAGNESIUM CITRATE, AND LOW-VOLUME PEG PLUS ASCORBIC ACID AS BOWEL PREPARATIONS FOR COLONOSCOPY: A PROSPECTIVE SINGLE-BLINDED RANDOMIZED CONTROLLED TRIAL

M. S. Park¹, B. S. Kim¹, W. K. Lee¹, M. A. Yang¹, J. U. Lee¹, S. H. Yun¹, S. H. Han¹, W. G. Oh¹, Y. J. Lee¹, G. M. Jung¹, Y. K. Cho¹, J. W. Cho¹, J. W. Kim¹

¹Division of Gastroenterology, Department of Internal Medicine, Presbyterian Medical Center, Jeonju, Republic of Korea

Contact E-mail Address: stromas@hanmail.net

Introduction: There are few data that compare among the three widely used bowel preparations: conventional 4L polyethylene glycol (4L PEG); sodium picosulfate and magnesium citrate(SPMC); and low-volume PEG plus Ascorbic acid(2L PEG + Asc).

Aims & Methods: The aim of this study is to compare among the three bowel preparations in the efficacy, tolerability, and safety.

228 patients undergoing outpatient elective colonoscopy were randomly assigned to one of the three bowel preparations by computerized randomization in a single-blinded prospective study. The three bowel preparations were as follows: Group A (n=78), 4L PEG solution; Group B (n=74), 3 sachets of SPMC as a split dose; or Group C (n=76), 2L PEG + Asc as a split dose. Additional stimulant laxative (Bisacodyl 10mg) was taken at the night before colonoscopy in all groups. All colonoscopy images were recorded into computed video files. One endoscopist blinded to the type of preparation gave a bowel cleansing score using recorded video files according to the Aronchick bowel preparation scale and Boston bowel preparation scale. And tolerability and safety were evaluated by a questionnaire immediately before the procedure.

Results: Age, gender distribution, history of DM, previous abdominal surgery, constipation in the three groups were not different significantly from each other. Data analysis showed that efficacy by Aronchick bowel preparation scale and Boston bowel preparation scale was not different significantly among three groups. There were no significant differences among the three groups in tolerability such as overall satisfaction by visual analogue score, consumed volume, willingness to repeat the same preparation. But, taste in SPMC group was significantly better than that in other two groups. The factors associated with safety such as abdominal distension, nausea, vomiting, general weakness were not significantly different among the three groups.

Conclusion: There were no significant differences among three bowel preparations in colonic cleansing efficacy. But, taste in SPMC group was significantly better than that in other two groups.

Disclosure of Interest: None declared

P0813 EVALUATION OF THE USEFULNESS OF BALLOON-ASSISTED ENDOSCOPY IN ERCP-RELATED PROCEDURES FOR PATIENTS WITH SURGICALLY ALTERED GASTROINTESTINAL ANATOMY

K. Kuraoka¹, Y. Okabe¹, T. Ushijima¹, Y. Ishida¹, Y. Sasaki¹, G. Sugiyama¹, R. Kaji¹, M. Fukahori¹, M. Yasumoto¹, O. Tsuruta¹, T. Torimura¹

¹Gastroenterology, Kurume University School of Medicine, Kurume, Japan

Contact E-mail Address: kuraoka_kei@kurume-u.ac.jp

Introduction: The endoscopic approach to pancreatobiliary disease with surgically altered gastrointestinal anatomy has conventionally involved very difficult procedures, but balloon-assisted endoscopy(BAE) has made them practical. In this study, we divided endoscopic retrograde cholangiopancreatography (ERCP)-related procedures performed in our hospital for patients with postoperative gastrointestinal reconstruction into 2 groups, a group using BAE and a group without BAE to retrospectively investigate the usefulness of BAE.

Aims & Methods: The study involved 198 cases (125 patients, including 101 males and 23 females) who underwent ERCP-related procedures performed in our hospital for patients with postoperative gastrointestinal reconstruction (excluding Billroth I reconstruction) between February 2002 and December 2014. Reconstructive procedures included 137 cases of Billroth II (B2), 39 cases of Roux-en-Y (R-Y), and 22 cases of post-pancreatoduodenectomy (or post-choledochojejunostomy). 64 patients had bile duct stones, 22 had malignant biliary strictures, 11 had bilioenteric anastomotic strictures, and 27 had other diseases (such as those who underwent detailed examination for pancreatic tumor). The cases were divided into group A, consisting of 149 cases of normal endoscopy (conventional direct-view endoscopy, colonoscopy, forward oblique viewing endoscopy, and backward oblique-viewing endoscopy), and group B, consisting of 49 cases of balloon endoscopy (single and double balloon endoscopy), to compare the rate of reaching the blind end, cannulation success rate, procedure completion rate, and complications between the groups.

Results: The rates of reaching the blind end were 85.2% (127/149) and 98.0% (48/49) in groups A and B. The cannulation success rates were 92.9% (118/127) and 75.0% (36/48) in groups A and B. The procedure completion rates were 76.5% (114/149) and 65.3% (32/49) in groups A and B. The rate of reaching the blind end was significantly higher in group B (P = 0.0159), whereas the cannulation success rate was significantly higher in group A (P = 0.0011). There was no difference in the procedure completion rate between the two groups. Complications included 4 cases of mild acute pancreatitis (3 cases in group A and one in group B), two cases of hyperamylasemia (both in group A), and 3 cases of intestinal perforation (two cases in group A and one in group B) (including two cases of emergency laparotomy [one case in group A and one in group B]).

Conclusion: The use of balloon endoscopy improved the rate of reaching the blind end in ERCP-related procedures for patients with postoperative gastrointestinal reconstruction. On the other hand, it is desired to develop not only the technology but also the devices for balloon-assisted ERCP to improve the cannulation success rate and procedure completion rate.

Disclosure of Interest: None declared

P0814 RISK FACTORS OF POST ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY PANCREATITIS AND EFFECTIVENESS OF PROPHYLAXIS IN JAPAN: A PROSPECTIVE MULTICENTER OBSERVATIONAL STUDY BY OSAKA PANCREAS FORUM (OPF)

K. Iwahashi¹, M. Shigekawa¹, A. Inoue², M. Oshita³, M. Inada⁴, K. Suzuki⁵, T. Tatsumi¹, T. Takehara¹

¹Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, ²Department of Gastroenterology, Osaka General Medical Center, ³Department of Internal Medicine, Osaka Police Hospital, ⁴Department of Gastroenterology, Toyonaka Municipal Hospital, ⁵Department of Gastroenterology, Osaka Saiseikai Senri Hospital, Osaka, Japan

Contact E-mail Address: k.iwahashi@gh.med.osaka-u.ac.jp

Introduction: Endoscopic retrograde cholangiopancreatography (ERCP) is an important procedure for diagnosis and management of pancreato-biliary disease. However, occurrence of complications, especially post-ERCP pancreatitis (PEP) is a huge problem. Rectal administration of 100 mg dose of non-steroidal anti-inflammatory drugs (NSAIDs) was reported to prevent PEP. However, only 25 or 50 mg of NSAIDs can be available and usable in Japan.

Aims & Methods: The aim of this study was to investigate the rate and risk factors of PEP and to assess effectiveness of prophylaxis in Japan. This was a prospective multicenter observational study. We created a common database of ERCP and each endoscopist entered data prospectively. Nineteen centers of Osaka Pancreas Forum joined this study. Study period was from October 2012 to February 2014. This protocol was approved by ethics committee at all participating centers. The definition of PEP was based on consensus criteria.

Results: A total of 2681 patients received ERCP during the study period. Patients who had undergone gastric or biliary surgery (166 patients) and who were unable to reach papilla because of perforation (3 patients), stenosis (6 patients), complications during ERCP (1 patient), or unable to attempt cannulation because of tumor invasion (2 patients) were excluded from analysis. In 2503 patients, the rate of PEP was 6.4%. Multivariate analysis revealed native papilla (odds ratio [OR] 2.96), female (OR 1.78), younger age (35-70) (OR 1.50 compared to age over 70), longer procedure time (more than 60 minutes) (OR 1.96 compared to time less than 30 minutes), pancreatogram (OR 2.57), double-guidewire cannulation (OR 1.87), endoscopic papillary balloon dilation (EPBD) (OR 2.91), biopsy or brush cytology on common bile duct (OR 1.74), transpapillary self-expandable metallic stent insertion (OR 4.71), bleeding after ERCP (OR 4.59), 25 mg administration of rectal diclofenac (OR 2.85 compared to no administration) were the significant risk factors of PEP, and history of acute pancreatitis (OR 0.33), pancreatic cancer (OR 0.53) were the significant protective factor of PEP.

Although 25 mg administration of rectal diclofenac was a significant risk factor, 50 mg administration of that was not a significant risk factor. Taking into account the bias that rectal diclofenac was selectively administered to patients who were considered vulnerable to PEP, 50 mg administration of rectal diclofenac was presumably effective to prevent PEP.

The frequency of PEP in the patients with pancreatic stent placement was significantly decreased compared to those without stent, when they were administered pancreatogram, EPBD, double-guidewire cannulation or biopsy or brush cytology on common bile duct.

Conclusion: We reported the rate and risk factors of PEP in Japan. Pancreatic stent may be effective to prevent PEP in patients with pancreatogram or procedures traumatic for papilla. Twenty-five mg rectal administration of NSAIDs may insufficient to prevent PEP. We need further investigation about administration dose of NSAIDs and its safety.

Disclosure of Interest: None declared

P0816 LEARNING CURVE OF ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY IN PATIENTS WITH SURGICALLY ALTERED ANATOMY

K. Hosono¹, A. Iwasaki¹, T. Sato¹, Y. Fujita¹, K. Kubota¹, A. Nakajima¹

¹Gastroenterology, Yokohama City University School of Medicine, Yokohama, Japan

Contact E-mail Address: hiro1017@yokohama-cu.ac.jp

Introduction: Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy is still challenging. In order to attain competence in performing this procedure, intensive training is necessary.

Aims & Methods: The study aim was to express development in ERCP in patients with surgically altered anatomy as a learning curve. We evaluate ERCP procedures by using single-balloon enteroscopy (SBE) at Yokohama City University Hospital (YCUH) in Japan between 2011 and 2014. In our facility, the same endoscopist performed the insertion into the target site, and ERCP procedures.

Results: 4 endoscopists were included in this study who have experienced more than 400 cases of the ERCP in normal anatomy. A total of 211 ERCP procedures were carried out in patients with surgically altered anatomy. The breakdown of surgical procedures was as follows: Roux-en-Y (R-Y) reconstruction (n=55 [26.1%]), pancreaticoduodenectomy (PD) (n=46 [21.8%]), hepaticojejunostomy (n=80 [37.9%]), and Billroth II reconstruction (n=30 [14.2%]). The overall success rate of reaching the target site was 94.3% (199 of 211 ERCP procedures). The overall mean time required to reach the target site was 22.8 min. The overall ERCP procedural success rate was 88.1% (186 of 211 ERCP procedures). When the data for all the individual endoscopist assessment periods were combined, the overall insertion rate and ERCP procedural success rate were seen to gradually increase with the total of ERCPs performed in patients with surgically altered anatomy. According to learning curve per block of 10 ERCPs, in the ERCP number of less than 20, insertion rate was 82.0%, ERCP success rate was 75.4%, in 20-30 ERCPs, insertion rate was 93.3%, ERCP success rate was 83.3%, in more than 30 ERCPs, insertion rate was 96.9%, ERCP success rate was 94.0%.

Conclusion: Our findings suggest that more than 30 cases were required for competence development in ERCP with surgically altered anatomy.

Disclosure of Interest: None declared

P0817 ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY IN ACUTE BILLIARY PANCREATITIS: SAFETY, EFFICACY AND IMPACT ON THE OUTCOME

L. C. R. Freitas¹, S. Fernandes¹, P. Santos¹, M. Moura¹, J. Carvalho¹, P. Sousa¹, R. Palma¹, T. Antunes¹, J. Velosa¹

¹Serviço de Gastrenterologia e Hepatologia, Centro Hospitalar de Lisboa Norte - Hospital de Santa Maria, Lisboa, Portugal

Contact E-mail Address: luisfreitas29@gmail.com

Introduction: The role of endoscopic retrograde cholangiopancreatography (ERCP) in the setting of acute billiary pancreatitis (ABP) is still a matter of debate.

Aims & Methods: To evaluate the safety and efficacy of ERCP in ABP and its impact on the outcome. We conducted a retrospective evaluation of ERCP performed in the setting of ABP, over a period of 11 years. Data from ERCP reports and clinical files was analyzed.

Results: Ninety-four cases were observed [Male sex 40 (42.6%); medium age 74.6+/- 12.8 years]. Seventy-three patients (77.7%) presented with severe ABP and 10 patients (10.6%) had associated cholangitis. ERCP was performed in a median of 3 days after ABP onset (range: 0-93), with 58 patients (61.7%) being submitted to early ERCP (<72 hours). Successful canullation was obtained in 92.6% of the cases. Coledocolithiasis was confirmed in 37 cases (39.4%). Spinctherotomy was performed in 83 patitens (91.5%). There were complications related to the procedure in 10 patients (10.6%): 8 post-sphincterotomy bleeding (controlled with endoscopic treatment) and 2 sedation related complications (reverted). Medium in-patient time was 11 days (range: 1-79). Early ERCP did not affect in-patient time. Thirty days mortality was 9.6%. Patients submitted to early ERCP didn’t have a significant lower mortality rate. Local complications (pancreatic necrosis, collections, pseudocysts and gastrointestinal bleegind) were seen in 44.7% of cases. There was no significant association between early ERCP and the development of local complications.

Conclusion: ERCP is safe in the setting of ABP. Performance of early ERCP did not affect in-patient time, mortality or the development of local complications.

Disclosure of Interest: None declared

P0818 ENDOSCOPIC PAPILLARY BALLOON DILATION WITH BILIARY SPHINCTEROTOMY : THE IDEAL TECHNIQUE FOR LARGE COMMON BILE DUCT STONES?

L. C. Lourenço¹, A. M. Oliveira¹, J. C. Branco¹, D. Horta¹, J. T. Canena¹, J. Reis¹

¹Serviço de Gastrenterologia, Hospital Prof. Dr. Fernando Fonseca, Amadora, Portugal

Contact E-mail Address: luisclourenco@gmail.com

Introduction: Endoscopic papillary balloon dilation (EPBD) with biliary sphincterotomy (BS) has been widely adopted when performing endoscopic retrograde cholangio-pancreatography (ERCP) for removing common bile duct stones larger than 10 mm.

Aims & Methods: The aim of this study was to compare results from EPBD with BS and BS alone (control group, CG) when treating large common bile duct stones.

We performed a rectrospective cohort study involving all cases of large common bile duct stones treated endoscopically in a single institution. The inclusion period was from 2011-2014 (4 years). EPBD was performed using a hydrostatic balloon ranging from 10 to 15 mm. We analysed efficacy (complete extraction, number of sessions needed, need for biliary stenting and lithotripsy), safety (complication rate) and recurrence.

Results: 110 patients were included. EPBD with EST was performed in 73 (66.3%), 61.6% were female and median age was 76 ±9.4 years. GC comprised 37 patients (33.7%) 54.1% were female and median age was 77 ± 8.2 (p=ns). In EPBD with EST group, 70.6% presented multiple common bile duct stones versus 48.9% in CG (p < 0.01). Mean diameter of the largest stone was 15.3 ± 4.2 mm (10-30 mm) versus 16.1 ± 6.3 mm (10-35 mm) in CG (p=ns). The stones were totally removed in a single session in 73.9% versus 40.5% ic CG (p < 0,01). Complication (8.2% vs 8.1%, p=ns) and recurrence (5.4% vs 5.4%) rates were comparable between the two groups.

Conclusion: EPBD with BS was safe and effective in removing large common bile duct stones. When compared with BS alone, this method allowed to remove all stones more frequently in a single session, with less need for biliary stenting and no increase in complications.

Disclosure of Interest: None declared

P0819 ENDOSCOPIC PAPILLARY LARGE BALLOON DILATION FOR TREATMENT OF LARGE BILE DUCT STONES ASSOCIATED WITH POST-PROCEDURE PANCREATITIS – MYTH OR REALITY?

L. C. Lourenço¹, A. Oliveira¹, J. C. Branco¹, D. Horta¹, J. T. Canena¹, J. Reis¹

¹Serviço de Gastrenterologia, Hospital Prof. Dr. Fernando Fonseca, Amadora, Portugal

Contact E-mail Address: luisclourenco@gmail.com

Introduction: Endoscopic papillary large balloon dilation (EPLBD) is a well-known procedure for the treatment of common duct stones larger than 10 mm. However, it is classified as an independent risk factor for post-procedure pancreatitits (PPP) and is still not recommended as an alternative to sphincterotomy in routine ERCP.¹

Aims & Methods: The aim of this study was to acess cases of PPP associated with EPLBD in our institution and correlate them patient and procedure related risks factors.

A rectrospective single-center cohort study was performed, including all cases of large common bile ducts (diameter more than 10 mm) treated using EPLBD with biliary sphincterotomy. Inclusion period was four years (2011-2014). To perform EPLBD, a hydrostatic baloon was used (10-15mm) during at least one minute. We defined PPP as a clinical syndrome consistent with acute pancreatitis with hyperamylasemia (level of amylase > 3 times the upper limit of normal) and increased epigastric pain persisting for ≥24 hours after the procedure. We analysed the risk factors for PPP (patient and procedure-related). Incidence and severity of PPP were studied.

Results: 73 patients were included in this study. 61.6% were female. Mean age was 76 ±9.4 years; 5.4%(n=4) were younger than 50 years. 4.1%(n=3) had a previous acute pancreatitis episode. None of the patients had normal bilirrubin levels or was suspected to have of Oddi sphincter disfunction. As for procedure-related risks factors, infundibulotomy was performed in 3 cases; pancreatography and pancreatic sphincterotomy were not performed. PPP prophylaxis was performed in a total of 3 patients (with administration of rectal indometacine in two and pancreatic stent in one). There was not a single case of PPP.

Conclusion: EPLBD with biliary sphincterotomy did not increase the incidence of PPP in patients with large bile duct stones. Its role as an independent risk factor probably deserves a more detailed analysis.

Disclosure of Interest: None declared

P0820 ERCP-GUIDED CHOLANGIO-PANCREATICOSCOPY USING A SINGLE-OPERATOR SYSTEM. AN APPRAISAL OF ITS CLINICAL VALUE BASED ON A UNIQUE EXPERIENCE

M. Reuterwall¹, L. Enochsson¹, L. Lundell¹, M. Konradsson¹, F. Swahn¹, M. Löhr¹, U. Arnelo¹

¹Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden

Contact E-mail Address: marcus.reuterwall@gmail.com

Introduction: The single-operator peroral cholangio-pancreaticoscopy enables direct visualization of duct lesions, biopsy, and therapeutic interventions in the biliary and pancreatic ductal systems. This device was introduced into clinical practice in 2007 under the trade name Spyglass (Spyglass direct visualization system, Boston Corp.). Ever since, it has been met with divergent reactions from being a valuable tool for use in diagnosis and therapy to basically offering no relevant information for the ensuing management of the patient. At Karolinska University Hospital the Spyglass technology was introduced early and has since then frequently been utilized according to a standardized protocol. Accordingly we have collected a unique experience and hereby we have critically analyzed the clinical usefulness of the technology in the diagnosis and treatment of biliary-pancreatic diseases.

Aims & Methods: All Spyglass procedures performed between March 1, 2007, and December 31, 2014, were retrospectively reviewed. Each procedure’s diagnostic yield and therapeutic value was evaluated using a 4 grade scale; where 1= No diagnostic or therapeutic value. 2=Information gained but did not affect clinical decision-making, if a therapeutic intervention was performed it did not alter the clinical course of the patient. 3= Information gained which had an impact on the clinical decision-making. Therapeutic intervention completed which had a subsequent impact on the course of the disease management. 4= Essential and critically important information was gained for the clinical decision-making. Therapy performed which solved the clinical problem leading to no further requirements for diagnostic or therapeutic modalities.

Results: Over approximately 8 years, 365 Spyglass procedures were performed. The overall post-procedural morbidity was 13%, where one case of severe pancreatitis was seen. The main indications for the procedure were; indeterminate stricture (28%), primary sclerosing cholangitis (20%), IPMN (17%), complex cholelithiasis (19%), chronic pancreatitis- including lithotripsy (8%) and miscellaneous in 7% of the cases. In 70% of our patients, the bile ducts were the main target whereas the pancreatic duct was aimed for in 22%. When the clinical usefulness was assessed according to the 4 grade scale, we found the Spyglass procedure of pivotal importance in 20% of the cases and grade 3 was scored in 36%. Information gained from, or therapy performed during the procedures did not affect clinical decision-making in 44% (grade 1 +2).

Conclusion: The single-operator peroral cholangio-pancreaticoscopy technique is an advanced technique for intraluminal visual inspection, and for therapeutic intervention of the biliary and pancreatic ducts associated with an increased risk of intra- and post-procedural adverse events, which shall be balanced against the information and options offered by the technique. We scored the value of the procedure as clinically significant in 56% of the cases, which signifies an important clinical role, mandating further investigation.

Disclosure of Interest: None declared

P0821 EVALUATION OF THE SHORT TYPE SINGLE- AND DOUBLE-BALLOON ENDOSCOPY ASSISTED ERCP IN PATIENTS WITH ALTERED GASTROINTESTINAL ANATOMY

M. Shimatani¹, M. Takaoka¹, M. Tokuhara¹, K. Kato¹, S. Miyamoto¹, H. Miyoshi¹, T. Ikeura¹, K. Okazaki¹

¹The Third Department of Internal Medicine, Kansai Medical University, Hirakata, Japan

Contact E-mail Address: shimatam@hirakata.kmu.ac.jp

Introduction: Background: The pancreatobiliary disease in patients with altered GI anatomy is difficult to be intervened by endoscopic diagnosis and therapies. The development of the balloon assisted endoscope (BAE) radically made the endoscopic approaches feasible. The BAE enabled the deep insertion to the blind end, and the short type BAE made ERCP-related interventions easier to accomplish due to its applicability to almost all the devices that are used for conventional ERCP.

Aims & Methods: Objective: We evaluated utility of ERCP using short DBE (DB-ERCP) and SBE (SB-ERCP).

Patients and Methods: Between February 2006 and February 2015, we performed DB-ERCP in total of 734 patients with surgical anatomic variations (734 procedures (pro.); 400 pro. (220 patients (pts.)) for Roux-en-Y reconstruction (R&Y), 112 pro. (79 pts.) for Billroth II gastrectomy (BII), 110 pro. (44 pts.) for pancreatoduoderectomy (PD), 79 pro (39 pts.) for pylorus preserving pancreaticoduodenectomy (PpPD), and 33 pro. (21 pts.) for others) and SB-ERCP in 26 patients with surgical anatomic variations (26 pro.; 12 pro. (12 pts.) for R&Y, 3 pro. (3 pts.) for BII, 4 pro. (4 pts.) for PD, 5 pro. (5 patients) for PpPD, and 2 pro. (2 pts.) for others). We retrospectively evaluated the success rate of reaching the blind end, the therapeutic success rate, and occurrence of complications.

Results: Result: Deep insertion of the short DBE to the blind end was successful in 665 of the 677 procedures (98.2%). The success rates by type of surgical anatomic variations were; 98.3%for R&Y, 99.1% for BII, 98.2% for PD, 97.5% for PpPD, and 100% for others. Whereas, deep insertion of the short SBE to the blind end was successful in 24 of the 26 procedures (92.3%). The success rate by type of surgical anatomic variations were; 98.1% for R&Y, 100% for BII, 100% for PD, 100% for PpPD, and 100% for others. As for 2 patients in whom short type SBE failed to reach the blind end, the procedure was successfully accomplished after switching the scope to short type DBE. Deep biliary cannulation in DB-ERCP was successful in 702 of the 772 procedures (97.2%). The success rates by type of surgical anatomic variations were; 98.0% for R&Y, 94.6% for BII, 99.1% for PD, 96.1% for PpPD and 93.5% for others. Therapeutic intervention was achieved in all of the 772 procedures in which deep cannulation was successful (100%). Whereas, deep biliary cannulation in SB-ERCP was successful in 22 of the 24 procedures (91.7%). The success rates by type of surgical anatomic variations were; 90.0% for R&Y, 100% for BII, 100% for PD, 100% for PpPD and 50% for others. The therapeutic success rate was 100%. Complications for all the DBE-applied procedures were observed in 40 of the 734 procedures (5.4%). The rates of occurrence by type of surgical anatomic variations were; 5.5% for R&Y, 11.6% for BII, 2.7% for PD, 2.5% for PpPD and 0% for others. For all the SBE-applied procedures, only 1 case of laceration was observed in patients with R&Y (3.8%).

Conclusion: Conclusions: ERCP by BAE is highly effective and safe for pancreatobiliary disease in patients with altered GI anatomy. Especially the short type BAE has proved its high performance, however further improvement is yet to be expected.

Disclosure of Interest: None declared

P0822 THE PRECUT RATE: IS THERE A CORRELATION WITH INCREASED COMPLICATION RISK? RESULTS-FROM THE GERMAN SPHINCTEROTOMY REGISTRY

M. Bechtler^1,*, A. Bachor², K. Westerhausen³, J. Labenz⁴ on behalf of ALGK Study Group, M. Maier⁵, R. Jakobs¹

¹Medizinische Klinik C, Klinikum Ludwigshafen, Ludwigshafen, ²BMI Heidelberg, Heidelberg, ³Hegau-Bodensee-Klinikum Singen, Singen, ⁴Jung-Stilling-Krankenhaus, Siegen, ⁵Knappschaftsklinikum Saar, Püttlingen, Germany

Contact E-mail Address: bechtlem@klilu.de

Introduction: Precut sphincterotomy seems to be associated with an increased complication rate. Whether this increased risk is caused by the procedure itself or by unfavourable circumstances under which it is used, is not yet clear. Early application of precut techniques might even reduce complications. Nevertheless, in 2006, the ASGE proposed a target precut rate below 15% as a possible quality indicator for ERCP. Data that show a clear correlation between precut rate and complication risk are missing, especially in a community setting. Here, we report results obtained by the German Sphincterotomy Registry.

Aims & Methods: Data obtained by the German Sphincterotomy Registry were analysed. 44 hospitals in Germany reported all patients that had undergone sphincterotomy during a one-year time frame between 2004 and 2007. Procedural variables concerning sphincterotomy setting and technique were collected prospectively and complication rates assessed before hospital discharge.

Results: 812 precut sphincterotomies and 4529 bile-duct sphincterotomies were included in the analysis. Participating hospitals reported between 26 and 247 sphincterotomies and 0 to 80 precut sphincterotomies during a given one-year period. The median precut rate between hospitals was 15.7% and ranged from 0.0 to 43.5%. Precut sphincterotomy was associated with a significantly increased complication rate of 17.6% vs. 9,0% of patients undergoing standard bile-duct sphincterotomy. An increased complication rate was observed for all subgroups of complications. However, a higher institutional precut rate was not associated with an increased complication risk (Spearman’s rank correlation coefficient: 0.04, p = 0.8)

Conclusion: In our Registry, which largely represents the common sphincterotomy practice in Germany in community settings, the institutional precut rates varied widely. This seems to reflect differences in the timing and indication for precuts. Although precuts are associated with a higher complication rate, there is no correlation between high institutional precut rate and the higher number of complications, which indicates that a precut itself is no risk factor. We therefore conclude that the precut rate should not be used as a quality indicator for the quality of intraprocedural ERCP.

Disclosure of Interest: None declared

P0823 THE COMBINED USE OF THE EUS-FNA AND BILIARY BRUSHING INCREASES ACCURACY OF CYTOLOGICAL DIAGNOSIS IN PANCREATOBILIARY MALIGNANCES

M. Bulajic¹, F. Vieceli², D. Berretti², L. M. Zoratti², S. F. Vadala' di Prampero², M. Marino², F. Toso², N. Panic³, G. Terrosu², M. Zilli²

¹Gastroenterology and Digestive Endoscopy, ²Academic Hospital “S. M. della Misericordia", Udine, Italy, ³University Clinic “Dr Dragisa Misovic-Dedinje", Belgrade, Serbia

Contact E-mail Address: bulajic.milutin@gmail.com

Introduction: Fifteen percent of patients with suspected pancreatobiliary malignancy that undergo surgery without a cytological assessment have a benign lesion. Cytological or histological diagnosis of pancreatobiliary malignancies before surgery is desirable in order to avoid unnecessary interventions.

Aims & Methods: We conducted a study in order to assess whether the combined use of biliary brushing and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has greater accuracy than the individual procedures in diagnosing pancreatobiliary malignancies before surgery. We recruited 25 patients with probable pancreatobiliary malignancy who underwent both biliary brushing and EUS-FNA at the Gastroenterology Unit of Azienda Ospedaliero-Universitaria Santa Maria della Misercordia, Udine (Italy). After brushing procedure, both collected material and cytology brush were sent for cytological analysis. The results of cytology were compared to the results of histology from surgical specimen, in order to evaluate the diagnostic accuracy of the two procedures.

Results: Histology of surgical specimen confirmed the diagnosis of pancreatobiliary malignancy in 24 of 25 patients, benign lesion caused by chronic pancreatitis was identified in one patient. Cytology from biliary brushing provided a correct diagnosis in 9 patients, with diagnostic accuracy of 36%, including the patient with a benign lesion. For the remaining 16 patients (54%), cytological diagnoses were as follows: indeterminate because of poor quantity or quality of the specimen in 15 patients, negative in one case (1 false negative). EUS-FNA provided a correct diagnosis in 18 patients with diagnostic accuracy of 72%, including the patient with a benign lesion. In 7 patients (28%) EUS-FNA didn’t provide any result because of the poor quality of the specimen. The combined diagnostic accuracy of both methods was 80% as they together provided a correct diagnosis in 20 patients. The additional diagnostic gain derived from the joint use of biliary brushing and EUS-FNA was 11 cases, compared to biliary brushing alone (+44%) and 2 cases compared to EUS-FNA alone (+8%).

Conclusion: The combined use of the EUS-FNA and biliary brushing results in increased accuracy of cytological diagnosing in pancreatobiliary malignancies. The biliary brushing as an addition to EUS-FNA should be considered in patients undergoing the endoscopic retrograde cholangiopancreatography (ERCP) in therapeutic purposes.

Disclosure of Interest: None declared

P0824 A NEW PROTOTYPE OF SHORT SBE FOR ERCP IN PATIENTS WITH SURGICALLY ALTERED ANATOMY

M. Kida¹, H. Yamauchi², K. Okuwaki², S. Miyazawa², T. Iwai², H. Kikuchi², M. Watanabe², H. Imaizumi², W. Koizumi²

¹Endoscopy Center, ²Gastroenterology, Kitasato University Hospital, Sagamihara, Japan

Contact E-mail Address: m-kida@kitasato-u.ac.jp

Introduction: The recent advent of balloon enteroscopy has achieved to perform ERCP in patients with surgically altered anatomy. However we have to use special long devices because of the long length of endoscope and can’t use wire-guided devices because of smaller channel. Then we have designed newly developed short-type prototype of single balloon enteroscope (SBE) and investigated its usefulness.

Aims & Methods: Then we have designed newly developed short-type prototype of single balloon enteroscope (SBE) and investigated its usefulness. From 2009 up to now, we have performed 233 ERCP in 160 patients (R-Y: 110, B- II: 50) with a new prototype of short enteroscope, which is 152 cm in length, 9.2 mm in diameter, and with 3.2 mm working channel. And we historically compared with a standard enteroscope which is used in 26 patients (R-Y: 18, B- II: 8) from 2007 to 2009, 200 cm, 9.2 mm, and with 2.8 mm working channel.

Results: Among the all sessions of ERCP, the rate of prototype and standard one of reaching the blind end was 88% (136/155), 84% (16/19) in R-Y, and 95 % (74/78), 100% (9/9) in B-II. The diagnostic success rates were 81%(80/99), 68% (11/16) in R-Y, and 84% (27/31), 89% (8/9) in B- II. The therapeutic success rates were 94% (75/80), 90% (9/10) in R-Y, and 96% (64/67), 100% (8/8) in B-II. The mean procedure time were 44.0 min., 50.6 min. in R-Y and 41.0 min., 38.4 min. in B-II. Because of the short length of endoscope, most conventional devices of ERCP could be used. And because the channel diameter was 3.2 mm, we could perform with wire guided devices. Hyperamylasemia and post-ERCP pancreatitis occurred 15.5% (24/155), 18.8% (3/16) and 5.2% (8/155), 12.5% (2/16) in R-Y, and 7.7% (6/78), 11.1% (1/9) and 0% (0/78), 0% (0/9) in B- II. Perforation occurred 2.6% (4/155), 0% (0/18) in R-Y, and 1.3% (1/78), 0% (0/9) in B- II.

Conclusion: Short-type SBE is effective for ERCP in patients with surgically altered anatomy and allows most conventional ERCP devices to be used.

Disclosure of Interest: None declared

P0825 USEFULNESS OF CONTRAST-ENHANCED EUS FOR INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM (IPMN) PATIENTS WITH MURAL NODULES

M. Fujita¹, T. Itoi¹, A. Sofuni¹, T. Tsuchiya¹, S. Tsuji¹, K. Kamada¹, R. Tanaka¹, R. Tonozuka¹, M. Honjo¹, S. Mukai¹, K. Yamamoto¹

¹Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan

Contact E-mail Address: fujita.com.com@gmail.com

Introduction: Endoscopic ultrasonography (EUS) is a modality with high resolution. Recently, EUS has made it possible to use new diagnostic imaging techniques, such as contrast-enhanced EUS (CE-EUS). Furthermore, CE-EUS has been reported to be useful in evaluating for Intraductal papillary mucinous neoplasm (IPMN ) with mural nodules.

Aims & Methods: The aim of this study is to evaluate the usefulness of CE-EUS relative to other imaging methods for diagnosing mural nodules of IPMN. 17 patients of IPMN who underwent CE-EUS were enrolled. EUS device system was HI VISION900 or HI VISION Avius (Hitachi Aloka Medical, Inc.) and, EG3870UTK endoscope (Pentax Co., Ltd.), or using ProSound SSDα-10 (Hitachi Aloka Medical, Inc.) and GF-UE260-AL5 endoscope (Olympus medical systems).The contrast agent used was Sonazoid® (DAIICHI SANKYO COMPANY). CE-EUS was performed after the B-mode EUS observation.

Results: The male/female ratio was 11:6, mean age was 61.8(38-78) years old, and mean cyst diameter was 20.5(8.2-50) mm, and mean diameter mural nodule was 7.3(2-16)mm . The modality by which mural nodules were detected was EUS for 5 patients, US for 5, CT for 4 and MRI for 3. Of the 17 patients, mural nodules were detected by EUS B-mode in 12 patients. B-mode imaging showed slightly high echo in 3, and low echo in 9 patients. The mural nodules in 5 of 12 patients was enhanced by CE-EUS. Seven mural nodules was not enhanced to diagnose as mucus lump or debris. Three of 7 patients with enhanced mural nodules were operated. The pathological diagnosis was Intraductal papillary mucinous carcinoma (IPMC) in 1 and Intraductal papillary mucinous adenoma(IPMA) in 2 patients.

Conclusion: CE-EUS is useful in evaluating whether mural nodule of IPMN or tumor.

Disclosure of Interest: None declared

P0826 ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY (ERCP) IN HUMANITARIAN MEDICAL CAMPAIGNS: EXPERIENCE OF A TERTIARY CARE ASSOCIATION IN REMOTE AREAS IN MOROCCO

M. Acharki¹, S. Rais¹, H. El Bacha¹, L. Kabbage¹, I. Ait Ahmed¹, A. Bargach¹, L. Amrani¹, M. Salihoun¹, N. Kabbaj¹

¹EFD Hepatogastroenterology Unit, Ibn Sina Hospital, Rabat, Morocco

Contact E-mail Address: soukaina.ra@gmail.com

Introduction: In developing countries, access to medical care for populations outside the large urban centers is often difficult. Endoscopic retrograde cholangiopancreatography (ERCP) is a gold standard in the management of pancreatobiliary diseases. It is often reserved for tertiary referral hospitals and until now, it is only available in a few centers in Morocco. The aims are to study the benefits of these humanitarian actions and to determine the challenges to achieve this kind of procedure in remote areas.

Aims & Methods: This is a prospective study carried out from April 2014 to April 2015, including all the medical campaign organized by “Action Urgence” Association (AU), in partnership with the Ministry of Health, local autorithies and other various partners, in public or private hospitals in the secluded areas of Morocco. We included all the patients who underwent ERCP. The characteristics collected were: age, gender, indication, outcome, complications and the main difficulties in realizing such procedures.

Results: During our study, AU organized 11 medical campaigns on a 12-month period all over Morocco, through mobile clinics involving many specialities such general surgery, pediatric surgery, ophthalmology and general medicine. Every event lasted an average of 3 days. 44 patients underwent ERCP: 30 women (68.1%) and 14 men (31.8%). The mean age was 48 years (11-80 years). The procedure was performed for treatment of choledocholithiasis in 36 cases (81.8%) (including 8 cholangitis and 5 pancreatitis), for a traumatic stenosis of the commun biliary duct (CBD) in 3 cases (6.8%), for a tumor stenosis requiring the placement of stents in 2 cases (4.5%), for a hydatid cyst fistulizing in the CBD in 2 cases (4.5%), and for 1 suspected sphincter oddities (2.27%). 5 patients (11.3%) underwent combined treatment (cholecystectomy under coelioscopy followed by endoscopic treatment) in the same procedure. The average length of hospital stay was 24 hours. We realized 35 sphincterotomies (79.5%), 6 infundibulotomies (13,6%) and 1 sphincteroclasy (2.27%). The biggest stone extracted measured 5/3 cm. treatment success was obtained from the first session in 38 patients (86.3%): 3 patients required performing a second procedure. Treatment by ERCP failed in 3 cases (6.8%). Complications were represented by 1 case of acute pancreatitis (2.27%). 1 death (2.27%) occurred as a result of severe cholangitis. The main difficulties met in these campaigns were: availability of the X-ray image intensifier, selection of patients and the difficulty of follow-up.

Conclusion: Performing ERCP in mobile hospitals provides access to tertiary centers care for population of remote areas. Our study demonstrates the feasibility of this procedure showing a good results and an acceptable complication rate. However, the organization of this kind of mobile unit requires an experimented multidisciplinary team and a significant investment.

Disclosure of Interest: None declared

P0827 AGE-APPROPRIATE SEDATIVE STRATEGY USING DEXMEDETOMIDINE AND MIDAZOLAM FOR ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY

N. Yamashita¹, O. Inatomi¹, H. Hasegawa¹, S. Bamba¹, M. Sugimoto², T. Tsujikawa³, A. Andoh¹

¹Division of Gastroenterology, ²Division of Endoscopy, ³Department of Comprehensive Internal Medicine, Shiga University of Medical Science, Otsu, Japan

Contact E-mail Address: osam@belle.shiga-med.ac.jp

Introduction: Endoscopic retrograde cholangiopancreatography (ERCP) often requires deep sedation because it is an invasive procedure. Although propofol has been widely used and accepted for ERCP, these agents occasionally cause respiratory depression. Dexmedetomidine (DEX), a highly selective α2-adrenoreceptor agonist with sedative effects and minimal respiratory effects, has recently been widely used for patients in the intensive care unit. However, its usefulness in endoscopic procedures remains unclear, particularly for elderly patients because of its effects on cardiac depression. In this study, we retrospectively investigated the safety and efficacy of DEX sedation during ERCP.

Aims & Methods: Among the patients who underwent ERCP from January 2013, 126 patients were sedated using DEX (intravenous infusion of 3.0 μg/kg/hr over 10 min followed by continuous infusion at 0.4 μg/kg/hr) with the addition of midazolam and pentazocine. Thirty elderly patients (> 81 years) were included in the study group. Additionally, pentazocine, midazolam, and propofol were administered as required to maintain a Ramsay sedation scale level of 4. For the control group, we collected information from patients who had undergone ERCP before January 2013 and who had been sedated with midazolam and pentazocine without DEX. The outcome measures were the amounts of midazolam and pentazocine administered, any adverse events associated with sedation, and patients hemodynamics.

Results: The incidence rate of decreased SpO₂ levels (3.5% vs. 11.6%, p = 0.04) and the median dose of additional midazolam and pentazocine were significantly lower in the DEX group than in the control group (5.2 mg vs. 12.5 mg and 7.5 mg vs. 11.4 mg, respectively; both at p < 0.001). There were no cases in whom propofol was required or the procedure had to be discontinued because of respiratory depression in the DEX group. The blood pressures and pulse rates were significantly lower in the DEX group than in the control group. The lower pressures and pulse rates were more common in the elderly patients in the DEX group. However, no patients required a vasopressor or suffered cardiac failure in the study group.

Conclusion: DEX reduced the incidence of respiratory complications and the total doses of other sedative agents that are concurrently administered. DEX can be used as an alternative to conventional methods for adequate sedation during ERCP even in elderly patients.

Disclosure of Interest: None declared

P0828 FULLY COVERED METAL STENTS VS MULTIPLE PLASTIC STENTING IN THE TREATMENT OF BILIARY STRICTURE AFTER LIVER TRANSPLANTATION: COST-EFFECTIVENESS ANALYSIS

P. Cantù¹, I. Parzanese¹, R. Rosa¹, A. Tenca¹, D. Conte¹, R. Penagini¹

¹Department of Pathophysiology and Transplantation, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy, Milan, Italy

Contact E-mail Address: paolo.cantu@policlinico.mi.it

Introduction: Multiple plastic stenting (MPS) is the traditional first-line endotherapy for anastomotic biliary stricture (ABS) after orthotopic liver transplantation (OLT). However, MPS requires multiple procedures to progressively maximize dilation of ABS, thus accounting for the high costs related to the procedures and hospital stay.

Aims & Methods: Aim was to compare, in patient with ABS, fully covered self expandable metal stent (FCSEMS) with MPS as concerns respective effectiveness, complications and costs. 25 OLT patients with clinically relevant ABS were retrospectively reviewed (#12) or prospectively collected (#13). FCSEMS and MPS groups were balanced for sex, age, etiology of cirrhosis and time from OLT. Eight or 10 mm large FCSEMS were used according to biliary duct diameter and removed after 4-6 months. Number of 10 Fr plastic stents was increased at 3 months interval up to maximal dilation. At stent removal, technical success was assessed by the easy passage of a balloon catheter through the anastomosis. During follow-up patients underwent clinical, laboratory and ultrasound abdominal examinations according to a standardized protocol. In case of technical failure or ABS recurrence, the patient was crossed-over to the other endoscopic procedure, whereas surgery was carried out when facing with endotherapy failure after cross-over. Overall costs included both procedures, stents and hospitalization.

Results:

	FCSEMSn=10	MPSn=15	p
ERCP, #pt (range)	2 (2-3)	4 (3-9)	<0.01
Technical success, n (%)	9 (90%)	14 (93%)	ns
Clinical success, n (%)	8 (80%)	14 (93%)	ns
Endoscopy costs (€) / pt,	4.432	6.509	<0.01
Hospitali stay costs (€) / pt,	2.400	6.720	<0.01
Treatment costs (€) / pt,	6.352	13.452	<0.01

Complications occurred in 2 (8.6%) cases after FCSEMS and in 3 (4.4%) cases after MPS (p=ns). Endotherapy duration was 4 (3-18) and 8 (4-55) months in the FCSEMS and MPS groups (p=0.001). After cross-over, endotherapy achieved clinical success in 24/25 (94%) pts at 19 (3-84) months.

Conclusion: Technical and clinical success and complication rate of FCSEMS and MPS were comparable, but FCSEMS achieved a significant reduction in costs, because of a lower number of procedures and a shorter length of hospital stay. These preliminary data suggested the role of FCSEMS as first-line endotherapy in ABS. A larger controlled randomized trial is currently ongoing to confirm the above findings.

Disclosure of Interest: None declared

P0829 TOLERABILITY OF COVERED METAL STENTS VS MULTIPLE PLASTIC STENTS FOR TREATMENT OF ANASTOMOTIC BILIARY STRICTURE AFTER LIVER TRANSPLANTATION. INTERIM ANALYSIS OF A RANDOMIZED STUDY

I. Parzanese¹, R. Rosa¹, A. Tenca¹, L. Kylänpää², M. Udd², O. Lindström², D. Conte¹, R. Penagini¹, P. Cantù¹

¹Department of Pathophysiology and Transplantation, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy, Milan, Italy, ²Department of Gastrointestinal Surgery, Helsinki University Central Hospital, Abdominal Center, Helsinki, Finland

Contact E-mail Address: paolo.cantu@policlinico.mi.it

Introduction: First-line endoscopic treatment of the anastomotic biliary stricture (ABS) is under debate. After orthotopic liver transplantation (OLT), high rate of technical and clinical success may be achieved by both multiple plastic stents (MPS) or covered self-expanding metal stent (CSEMS). However tolerability of these two endotherapies has never been evaluated, deserving integration in the ongoing randomized studies on effectiveness.

Aims & Methods: This prospective series was aimed at evaluating tolerability and effectiveness of CSEMS vs MPS in ABS management. From June 2013, 23 OLT pts with ABS were randomized to MPS or CSEMS in two Academic Centres. Age, sex, etiology of cirrhosis, time from OLT and severity of ABS were balanced between study groups. Tolerability was evaluated on: intensity of abdominal pain (Numerical Rating Scale, NRS), use of analgesics, need of pethidine, length of hospital stay (LOS ≥ 1 day) and early removal of stent for persistent pain. NRS was administered 1 day before ERCP (basal value) and daily after procedure with a thirty-day diary. To overcome intrapatient variability, for each value reported after maximal MPS or CSEMS, ΔNRS(daily value – basal) was evaluated. An easy transanastomotic passage of a balloon inflated at the diameter of native bile duct was considered as technical success, whereas absence of symptoms, cholestasis and bile duct dilation at US tested for clinical success. Tolerability data were correlated with severity of ABS, maximal diameter of stenting and type of endotherapy. ΔNRS > 4 was considered as relevant abdominal pain. Data were expressed as median ± IQ range. Mann-Whitney and Chi-squared (χ²) tests were used.

Results: Tolerability data are summarized in the Table.

Parameter		MPS(n=10)¹	CSEMS(n=12)	p
Pain	Pt # (%)	2 (20)	8 (67)	<0.05
ΔNRS (range)	0 (-2:9)	3 (-1:8)	ns
ΔNRS > 4	Pt # (%)	2 (20)	5 (42)	ns
Need for:
- drugs	Pt# (%)	2 (20)	8 (67)	<0.05
- pethidine	Pt # (%)	0 (0)	4 (33)	<0.05
Prolongation of LOS	Pt # (%)	1 (10)	6 (50)	<0.05

¹One patient was excluded because of mild post-ERCP pancreatitis

Intensity of pain and use of drugs did not differ for other scheduled recordings. No patient underwent early stent removal for persistent pain and treatment is still ongoing in two MPS and three CSEMS pts. Technical success was achieved in 7 of 8 MPS pts (87%) and in 8 of 9 CSEMS ones (89%, p=ns). In one case, MPS failed due to bleeding and cross-over to CSEMS was needed for ABS treatment and hemostasis as well; in one case CSEMS failed for early migration and cross-over to MPS was needed due to cholangitis. Clinical success was achieved in 5 of 8 MPS patients (62%) at 7 mos (3-8) and in 7 of 9 (77%) CSEMS patients at 2 mos (1-16). ABS recurred in two MPS cases at 3 and 5 mos; the first was retreated with CSEMS and the other with maximal MPS. Technical and clinical success rates were not related to characteristics of population. Use of pethidine was associated with a more severe grade of ABS (>90%) (p=0.04) and use of CSEMS but was not correlated with maximal diameter of stenting.

Conclusion: Due to its more rapid expansion, the need for analgesics was higher with CSEMS leading to a longer hospital stay. Noteworthy, the occurrence of abdominal pain did not impact on the success rate of endotherapies.

Disclosure of Interest: None declared

P0830 BALLOON ASSISTED ERC - AN ALTERNATIVE IN BILE DUCT DISORDERS IN PATIENTS WITH SURGICALLY ALTERED ANATOMY

P.-O. Stotzer¹

¹Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden

Contact E-mail Address: per-ove.stotzer@vgregion.se

Introduction: Bile duct disorders in patients with surgically altered anatomy are a growing problem. ERC performed with a ballon assisted enteroscope has been reported as a way to handle these problems.

Aims & Methods: To evaluate double-ballon assisted ERC in postsurgical patients.

ERC were performed with a double-balloon enteroscope with a working channel of 2.8 mm. All examinations were performed by a single investigator.

Results: Thirty-six investigations were performed in 29 patients, 15 women and 14 men. Mean age was 53 year, range 17 – 73. Surgery altering the anatomy was: Liver transplantation (n=13), Whipple-procedure (n=5), gastric by-pass (n=5), Billroth II (n=4) and Bile duct reconstruction after iatrogenic damage (n=3). Seventeen had a biliodigestive anastomosis and 12 had an intact papilla. Mean procedure time were 86 min. 23/36 procedures were performed in full anesthesia. Overall success rate per procedure were 24/36 (67 %) and per patient 22/29 (76 %). Following procedures were successfully performed: Brush- cytology (n=4), papillotomy + dilatation of the papilla + stone-extraction (n=3), papillotomy + stone-extraction (n=2), stone-extraction (n=2), dilatation of the hepaticojejunostomy + stone-extraction (n=2), stent-removal (n=2), stent-insertion (n=1). Five subjects had bile ducts without pathology, of whom two had an inconclusive MRCP and 3 had a false positive MRCP. Three patients had complications: one had a bowel perforation, one mild pancreatitis and one subject had post-procedural abdominal pain.

Conclusion: Balloon assisted enteroscopy is a feasible way to gain access to bile ducts in patients with altered anatomy. However, it is cumbersome and should probably be used in selected cases.

Disclosure of Interest: None declared

P0831 THE POLYMORPHISMS AT PRSS1-PRSS2 AND MORC4 LOCI AND THE RISK OF POST-ERCP PANCREATITIS

P. Angsuwatcharakon¹, P. Sodsai¹, R. Rerknimitr¹, N. Hirankarn¹

¹Medicine, Chulalongkorn University, Bangkok, Thailand

Contact E-mail Address: borndeb@yahoo.com

Introduction: The risks of post-ERCP pancreatitis (PEP) are identified as patient- and procedure-related factors. Recent data show that the polymorphisms of PRSS1-PRSS2 (rs10273639) and MORC4 (rs12688220) are associated with recurrent acute pancreatitis and chronic pancreatitis. However, the genetic contribution for PEP is still unclear.

Aims & Methods: We aim to evaluate the association between these polymorphisms and post-ERCP pancreatitis in order to improve better prognosis and better care for these patients. This is a retrospective, case-control study includes 49 cases and 101 controls that had age-, procedure-, and risk of PEP-matched with the cases in 1:2 fashion. The PEP was diagnosed and graded for severity according to the standard consensus, and the risk factors of PEP were identified according to ESGE guideline. Polymorphisms at rs10273639 and rs12688220 were evaluated by TaqMan technique and were identified in 133 (40 cases & 93 controls) and 150 patients repectively.

Results: The demographic data between 2 groups are not significantly different. The genotype frequencies of PRSS1-PRSS2 (TT, TC, CC) are 26, 13, and 1 vs 67, 25, and 1 in cases and controls, respectively (p = 0.642). The genotype frequencies of MORC4 in female (TT, TC, CC) are 8, 23, and 5 vs 12, 27, and 21 in cases and controls, respectively (p = 0.071). The genotype frequencies of MORC4 in male (T, and C) are 5, and 8 vs 21, and 17 in cases and controls, respectively (p = 0.468). The allelic frequency of MORC4 in combination of both genders (T, C) are 44, and 41 vs 72, and 86 in cases and control, respectively (p = 0.431). In PEP cases, the allelic frequencies of PRSS1-PRSS2 (T, and C) are 59, and 13 vs 6, and 2 in mild and moderate/severe cases, respectively (p = 0.633). The allelic frequencies of MORC4 (T, and C) are 38, and 39 vs 4, and 4 in mild and moderate/severe cases, respectively (p = 0.972).

Table 1.

Baseline characteristic and results of polymorphisms of PRSS1-PRSS2 and MORC4

	Case (n = 49)	Control (n = 101)	P-value
Age, mean (SD) (years)	60.3 (14.1)	60.0 (15.4)	0.901
Gender (%female)	72%	61%	0.145
Risk group (%high risk)	67%	63%	0.632
PRSS1-PRSS2 genotype frequency* TT TC CC	26131	67251	0.642
MORC4 genotype frequency TT (female)/ T (male) TC (female) CC (female)/ C (male)	8/5235/8	12/212721/17	0.071 (female)/ 0.468 (male)
PRSS1-PRSS2 allelic frequency* T C	6515	15927	0.493RR (95%CI) = 0.81(0.52-1.28)
MORC4 allelic frequency T C	4441	7286	0.431RR (95%CI) = 1.17(0.83-1.66)

* n = 113 (40 cases and 93 controls)

Conclusion: Polymorphisms at PRSS1-PRSS2 and MORC4 are not associated with the risk or severity of post-ERCP pancreatitis.

Disclosure of Interest: None declared

P0832 A RANDOMIZED ASSESSMENT OF A SEMI-DISPOSABLE, FIBEROPTIC SINGLE-OPERATOR CHOLANGIOSCOPE WITH A FULLY-DISPOSABLE, DIGITAL SINGLE-OPERATOR CHOLANGIOSCOPE IN A BILIARY TRACT BENCH MODEL

R. J. Shah¹, H. Neuhaus², M. Parsi³, D. N. Reddy⁴, D. K. Pleskow⁵

¹Gastroenterology, University of Colorado, Aurora, United States, ²Gastroenterology, Evangelisches Krankenhaus Dusseldorf, Dusseldorf, Germany, ³Gastroenterology, Cleveland Clinic Foundation, Cleveland, United States, ⁴Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India, ⁵Gastroenterology, Beth Israel Deaconess Medical Center, Boston, United States

Contact E-mail Address: raj.shah@ucdenver.edu

Introduction: A new four-way tip deflection digital single-operator cholangioscope (DSOC); (SpyGlass DS ™ Boston Scientific, MA) has a complementary metal-oxide semiconductor (CMOS) chip for higher resolution, magnification, and field of view; it has a thin copper cable for digital transmission and lacks a separate fiber optic probe which may improve catheter tip articulation. The processor is portable for simplified setup.

Aims & Methods: The aim was to compare maneuverability between the fiber optic SOC (FSOC) and DSOC. A biliary tract model devised after input from the authors (PULSE R&D, Southampton, PA) contained three fixed “left intrahepatic” (LIHD) tracts at varying angles with colored terminal targets and a variable “common bile duct” (CBD) and “right intrahepatic” (RIHD) tracts each with two ∼4mm colored targets, respectively, and multiple configurations. Seven targets were placed on the circumference. Investigators were blinded to target locations. Runs were randomized and timed with a goal to target each colored area using forceps (Spybite^TM). Definitions: Visual Success – identifying targets; Targeting Success – touching a target with a forceps; Complete Run – touching all targets with a surrogate metric for futility of 20 minutes. Image quality and ease of use was recorded on a visual analog scale (VAS) of 0 to 10. Time to completion was analyzed using a t-test and a negative binomial model was used to test visual and targeting success between the groups (SAS 9.4).

Results: A total of 39 runs were completed by five expert investigators; 2 were excluded due to inadequate randomization and 37 (20 DSOC, 17 FSOC) were analyzed. DSOC was superior to FSOC in terms of Visual (96% vs. 66%, p<.001) and Targeting Success (6.6 vs. 4.5, p = .007) and Complete Runs (13/20 vs. 0/17, p <.001). Five FSOC trials terminated due to futility. For fixed LIHD, DSOC achieved higher targeting success compared to FSOC (2.6 vs. 1.1, p<.001); no difference was seen with RIHD and CBD targets (4.0 vs. 3.4, p = 0.39). DSOC run completion time (minutes) was faster than FSOC (mean 10.1 vs. 15.4, p < 0.001). By VAS (0-10), investigators reported superior image quality and ease of use with the DSOC.

TABLE 1.

Comparison of Fiberoptic Single-Operator Cholangioscopy with Digital Single-Operator Cholangioscopy

	Fiberoptic SOC (n=17)	Digital SOC (n=20)	P-value
Percentage of Targets Visualized (n)	66% (79/119)	96% (134/140)	<0.001
Variable (n)	90% (61/68)	100% (80/80)	<0.001
Fixed (n)	35% (18/51)	90% (54/60)	<0.001
Successful Targeting per Run	4.47+/-0.72	6.55+/-0.69	0.007
Variable Targets	3.41+/-0.71	3.95+/-0.22	0.394
Fixed Targets	1.06+/-0.24	2.60+/-0.68	<0.001
Time of Run	15.35+/-4.00	10.05+/-3.72	<0.001
VASImage Quality	4.25+/-0.96	8.25+/-0.50	<0.001
VASEase of Use	4.75+/-0.96	8.50+/-0.58	<0.001

Conclusion: 1) In this benchtop biliary tract model that simulated CBD and intrahepatic ducts with variable and fixed colored targets, respectively, DSOC performed superiorly to FSOC with respect to image quality and maneuverability based on the metrics of visualization, targeting, and complete runs. 2) Whether these advantages will translate to higher clinical success or be appreciated by non-experts requires further investigation.

Disclosure of Interest: R. Shah Consultancy: Boston Scientific Endoscopy, H. Neuhaus Consultancy: Boston Scientific Endoscopy, M. Parsi: None declared, D. N. Reddy: None declared, D. Pleskow Consultancy: Boston Scientific Endoscopy

P0833 EUS-GUIDED GALLBLADDER DRAINAGE : AN ALTERNATIVE TREATMENT FOR ACUTE CHOLECYSTITIS

J. Privat¹, H. Demmak¹, I. Patrascan¹, L. Bianchi¹

¹Gastroenterology, Centre Hospitalier de Vichy, Vichy, France

Contact E-mail Address: jocelyn.privat@ch-vichy.fr

Introduction: Therapeutic EUS has greatly improved since the past years. Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD is one of the next challenges in the field of therapeutic EUS and may become an alternative to the conventional percutaneous transhepatic gallbladder drainage for acute cholecystitis in non-surgical candidates.

Aims & Methods: This is a single center case-study of 10 EUS-GBD. All cases were reviewed retrospectively from June 2014 to March 2015. Surgery was contraindicated for all patients, most being in a palliative situation. Primary outcomes measured were technical and clinical success. Secondary outcomes were adverse events and recurence of cholecystitis.

Results: 10 patients underwent EUS-GBD with a mean age of 79 (62-92, 3M/7F). The mean follow up time was five months (3 days - 8 months). 7 cases were performed for malignant disease (pancreatic and biliary cancers). Transmural acces was prefered, offering better stability, from duodenal bulb in 8 cases and from gastric antrum in 2 cases. EUS-GBD was achieved by placement of combined metallic and plastic stents with stent in stent technique (Boston Scientific WallFlex™ biliary fully covered metallic stent 10mm x 4cm with double pigtail plastic stent 7Fr x 5cm). Technical and clinical success occured in all cases with no early adverse event. A delayed stent migration occured in one case at 3 week and was discovered by recurrence of cholecystitis, managed conservatively.

Conclusion: EUS-GBD appears to be a feasible, effective and safe technique for the treatment of acute cholecystitis in high risk patients. Further studies are needed to confirm theses results and etablish safety of this procedure. Device and technical options needs also to be specified.

Disclosure of Interest: None declared

P0834 OBSERVATIONAL, MULTICENTER STUDY TO EVALUATE THE DIAGNOSTIC ACCURACY OF A NEW EUS 20-GAUGE NEEDLE FOR INTRAINTESTINAL AND EXTRAINTESTINAL LESIONS

J. Iglesias-Garcia¹², P. van Riet³, A. Larghi⁴, M. Giovannini⁵, M. Petrone⁶, J. Lariño-Noia¹², J. Poley³, E. Bories⁵, E. Davizzi⁶, I. Abdulkader¹, G. Monges⁵, K. Biermman³, C. Doglioni⁶, G. Rindi⁴, G. Costamagna⁴, P. Arcidiacono⁶, M. Bruno³, J. E. Domínguez-Munoz¹

¹University Hospital of Santiago de Compostela, ²Foundation for Research in Digestive Diseases, Santiago de Compostela, Spain, ³Erasmus MC, University Medical Center, Rotterdam, Netherlands, ⁴Catholic University, Rome, Italy, ⁵Paoli-Calmettes Institute, Mareilles, France, ⁶Vita Salute San Raffaele University, Milan, Italy

Contact E-mail Address: info@fienad.org

Introduction: Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) is an accurate technique for sampling intraintestinal and extraintestinal lesions. However, cytology possesses certain limitations, which may be overcome if histological specimens are provided to the pathologist.

Aims & Methods: The aim of the study was to evaluate the feasibility and accuracy of a newly developed 20-gauge histology needle. METHODS: Retrospective analysis of a prospectively collected data base including patients who underwent EUS-guided biopsy with the 20-gauge ProCoreTM histology needle with reverse bevel (3-HD-20) for the evaluation of intraintestinal or extraintestinal lesions. EUS procedures were performed under sedation with linear echoendoscopes (Olympus and Pentax).

Samples recovered into cytological solution or formalin and processed for histological evaluation. Results were compared to the gold standard of surgical histopathology, or global pathological, clinical and radiological assessment, and follow-up in non-operated cases. Feasibility of the procedure and different technical aspects were recorded. Percentage of samples suitable for histological evaluation and the overall diagnostic accuracy were evaluated. Results are shown as mean and standard deviation or 95% confidence interval.

Results: 51 patients (mean age 62.2 years, range 36-83 years, 26 male) were included. A total of 52 lesions were attempted to be sampled (mean size

31.88 ± 12.4mm). Indications were pancreatic mass (n=30), intraabdominal lymph nodes (LN) (n=6), subepithelial lesions (n=6), liver mass (n=3) and 1 cases of mediastinal LN, lung cancer, rectal mass, esophageal lesion, hiliar

mass, intraabdominal mass and a left suprarenal gland mass. Lesions were accessed from esophagus in 3 cases, stomach in 27 cases, bulbous in 15 cases, second part of the duodenum in 6 cases and from the rectum in 1 case.

EUS-guided biopsy was feasible in 50 cases (96.1%), with a mean of 1.7 passes (range 1-4). From 50 cases completed, sample quality was adequate for histological assessment in 46 lesions (92.0%). In the intention to treat analysis, diagnostic yield was 84.6% (95%CI: 72.5-91.9) and in per protocol analysis, diagnostic yield was 88.0% (95%CI 76.2-94.4). There were 2 (3.9%) mild complications (intraparietal hematomas at the place of FNB).

Conclusion: The EUS-guided biopsy with the 20-gauge ProcoreTM histology needle provides with a very good core sample for histological evaluation allowing a high histopathological diagnostic accuracy.

Disclosure of Interest: J. Iglesias-Garcia Conflict with: International Advisor Cook, P. van Riet Conflict with: International Advisor Cook, A. Larghi Conflict with: International Advisor Cook, M. Giovannini Conflict with: International Advisor Cook, M. Petrone: None declared, J. Lariño-Noia: None declared, J. Poley Conflict with: International Advisor Cook, E. Bories: None declared, E. Davizzi: None declared, I. Abdulkader Conflict with: International Advisor Cook, G. Monges: None declared, K. Biermman: None declared, C. Doglioni: None declared, G. Rindi: None declared, G. Costamagna: None declared, P. Arcidiacono Conflict with: International Advisor Cook, M. Bruno Conflict with: International Advisor Cook, J. E. Domínguez-Munoz: None declared

P0835 OBSERVATIONAL, PROSPECTIVE, SINGLE-CENTER COMPARATIVE STUDY BETWEEN STRAIN HISTOGRAM AND STRAIN RATIO FOR THE QUANTIFICATION OF ENDOSCOPIC ULTRASOUND (EUS)-GUIDED ELASTOGRAPHY OF SOLID PANCREATIC LESIONS

J. Iglesias-Garcia¹², J. Lariño-Noia¹², I. Abdulkader¹, J. E. Domínguez-Munoz¹²

¹University Hospital of Santiago de Compostela, ²Foundation For Research in Digestive Diseases, Santiago de Compostela, Spain

Introduction: Quantitative EUS-elastography allows quantifying tissue stiffness during a standard EUS examination. Elastography is a very accurate technique supporting the diagnosis of malignancy in solid pancreatic lesions. Elastography result may be analyzed either by strain ratio (SR) or strain histogram (SH).

Aims & Methods: Aim of the study was to evaluate the accuracy of SR and SH for the differential diagnosis of solid pancreatic masses. METHODS: A prospective, observational, comparative study was designed. 162 consecutive patients (mean age 63 years, range 17-89, 98 male), with a solid pancreatic mass at EUS were prospectively included. Elastography was performed with linear Pentax-EUS and Hitachi-Preirus. For SH, the tumor area was selected and analyzed. The mass (area A) and a peripancreatic soft reference area (B) were selected for SR analysis (quotient B/A). Final diagnosis was based on surgical histopathology, or EUS-FNA/FNB and global clinical and radiological assessment at follow-up in non-operated cases. Data are shown as mean (95%CI) and analyzed by ANOVA. Diagnostic accuracy was calculated by drawing the corresponding ROC curves.

Results: Size of masses was 35.0 ± 17.8mm. Tumors were located in the head (n=107), body (n=45) and tail (n=10) of the pancreas. Final diagnosis was pancreatic adenocarcinoma (n=106), malignant neuroendocrine tumor (NET) (n=9), benign NET (n=4), pancreatic metastasis (n=9), and inflammatory masses (n=34). Results of SH were 84.42 (76.4-92.45) in benign masses and 26.33 (24.7-28.0) in malignant tumors (p < 0.001). SR was 8.73 (5.21-12.2) in benign masses and 43.90 (37.8-50.0) in malignant tumors (p < 0.001). Sensitivity and specificity of SR for diagnosing malignancy were 100% and 92.1% (cut-off 9.74) (AUC=0.942; 95%CI 0.88-1), and of SH 92.1% and 100%, respectively (cut-off 62.0) (AUC=0.961; 95%CI 0.91-1). There were no differences in terms of diagnostic yield between both methods.

Conclusion: Elastography is a very useful tool for the diagnosis of malignancy in solid pancreatic masses. SR and SH are equivalent in this setting.

Disclosure of Interest: None declared

P0836 A COMPARATIVE STUDY OF ENDOSCOPIC ULTRASOUND-GUIDED CHOLEDOCHODUODENOSTOMY AND TRANSPAPILLARY STENT PLACEMENT IN PATIENTS WITH MALIGNANT BILIARY OBSTRUCTION AS THE FIRST-LINE TREATMENT

K. Kawakubo¹, H. Kawakami¹, M. Kuwatani¹, S. Haba¹, Y. Abe¹, S. Kawahata¹, Y. Kubota¹, K. Kubo¹, N. Sakamoto¹

¹Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan

Contact E-mail Address: kkawakubo-gi@umin.ac.jp

Introduction: Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) has gained popularity as an alternative to percutaneous biliary drainage in patients with failed ERCP. There was no comparative study as the first-line treatment for distal malignant obstruction between EUS-CDS and endoscopic trasnpapillary stenting (ETS).

Aims & Methods: The aim of this study was to compare the clinical efficacy and safety of EUS-CDS and ETS in patients with distal malignant biliary obstruction as the first-line treatment. Before May 2012, 56 patients underwent ETS, after that, 26 patients underwent EUS-CDS as the first-line treatment for the management of distal malignant biliary obstruction. We retrospectively compared the clinical success rate, adverse event rate and reintervention rate.

Results: Clinical success rate was equivalent in both groups (EUS-CDS; 96.2, ETS; 98.2%, p=0.54). Procedure time was significantly shorter in EUS-CDS than in ETS (19.7 vs 30.2 min, p < 0.01). The rate of overall adverse events was not significantly different between groups (EUS-CDS; 27%, ETS; 36%, p=0.46). Post-procedure pancreatitis was only observed in ETS group (0% vs 16%. P=0.03). Reintervention rate at one year was 16.6 and 13.6% in EUS-CDS and ETS, respectively (p=0.50).

Conclusion: EUS-CDS could be considered the first-line treatment of patients with distal malignant biliary obstruction due to the short procedure time and no risk of pancreatitis.

Disclosure of Interest: None declared

P0837 ENDOSCOPIC ULTRA SOUND-GUIDED INTRAHEPATIC PORTOSYSTEMIC SHUNT (EGIPS) IN A LIVE PORCINE MODEL

L. Poincloux^1,2,*, P. Chabrot³, M. Goutte¹, J. Genes⁴, L. Boyer³, G. Bommelaer¹, A. Abergel^1,2

¹Digestive Disease, NHE - CHU of Clermont-Ferrand, ²ISIT (Image Sciences for Innovations Techniques), Auvergne University/CNRS, ³Radiology, GM - CHU of Clermont-Ferrand, Clermont-Ferrand, ⁴Digestive Disease, Hospital of Riom, Riom, France

Contact E-mail Address: lpoincloux@chu-clermontferrand.fr

Introduction: Interventional EUS is a promising novel approach in intravascular interventions. The aim of this study was to assess the feasibility and the safety of EUS-Guided Intrahepatic Portosystemic Shunt (EGIPS) in a live porcine model.

Aims & Methods: The Left Hepatic Vein (LHV) or the Inferior Vena Cava (IVC) was punctured with a needle which was advanced into the Portal Vein (PV). A guide-wire was inserted into the PV and an intrahepatic fistula between LHV and PV was created with a needle-knife. A portal pressure was recorded. The intrahepatic fistula was dilated with a balloon and an expandable biliary metal stent was deployed between LHV and PV under sonographic and fluoroscopic observation. A final portocavography validated the permeability of the stent. Euthanasia allowed necropsies.

Results: A portosystemic stenting was technically achieved in 19/21 cases. Final portocavography confirmed the stent permeability between the PV and the LHV or the IVC in 17 cases (efficacy of 81%): 4 stents were dysfunctionning because 2 were thrombosed and 2 too proximal. Portal pressure before and after shunt was achieved in 20/21 cases. Necropsies revealed that 19/21 procedures were transesophageal, and 2 were transgastric. We observed 1 hemoperitoneum and 1 pneumothorax in pig 5, 1 hemothorax in pigs 6 and 20. The morbidity was 14.2% (3/21 animals).

Conclusion: EGIPS in a live porcine model was technically feasible in 91%, functional in 81% and with a morbidity of 14.2%. EGIPS should be assessed in portal hypertension pig models and could become an option to TIPS failure.

Disclosure of Interest: None declared

P0838 NEEDLE-BASED CONFOCAL LASER ENDOMICROSCOPY (NCLE) FOR THE DIAGNOSIS OF PANCREATIC MASSES: VALIDATION OF THE DESCRIBED CRITERIA (CONTACT STUDY)

M. Giovannini¹, F. Caillol¹, F. Poizat¹, G. Monges¹, L. Palazzo², D. Lucidarme³, B. Pujol⁴, A. I. Lemaistre⁵, B. Napoleon⁴

¹Institut Paoli Calmettes, Marseille, ²Clinique du Trocadero, Paris, ³Hopital Saint Philibert, Lomme, ⁴Hopital Jean Mermoz, ⁵Centre Leon Berard, Lyon, France

Contact E-mail Address: giovanninim@wanadoo.fr

Introduction: Needle-based Confocal Laser Endomicroscopy (nCLE) is an imaging technique, which enables microscopic observation of solid organs, in vivo and in real-time, during an EUSFNA procedure. The CONTACT study (Clinical evaluation Of NCLE in The lymph nodes Along with masses and Cystic Tumors of the pancreas) aims at building an image atlas, define interpretation criteria for nCLE images in the pancreatic masses and propose a first validation of these criteria.

Aims & Methods: 3 centres in France (7 investigators) took part in this prospective study. Any pancreatic mass studied by EUSFNA could be imaged by nCLE, but if a patient had multiple masses, only one of them could be imaged.

40 patients with a pancreatic mass were included prospectively during the study (June 2012 to March 2014).Out of these 40 patients, 33 were evaluable : 23 adenocarcinomas, 3 neuroendocrine neoplasms, 1 pseudopapillary tumor and 5 chronic pancreatitis.

Based on the previously described criteria (1), two validations of these criteria have been performed : one by the physicians who described the criteria (M.G, F.C, F.P, G.M), the second one by three gastroenterologists and one pathologist (B.N, B.P, L.P, A.I.L) external to the definition of the criteria.

For this evaluation, physicians were completely blinded to the clinical history of the patient, and the EUS examination. They only had the nCLE recorded sequence.

For each of the 33 patients, they were asked to give a diagnosis based on the existing criteria (1). When agreement between investigators was not complete, a consensus was reached.

Results: For the first validation (by investigators who established the classification- Group 1): IOA was perfect (k=1) – agreement between the observers was complete in 70 % of the cases. A consensus was obtained for the other 30 %.

For the second validation (by external investigators- Group 2) : IOA was moderate (k=0.55) – Agreement between the observers was complete in 40 % of the cases. A final consensus was obtained for the other 60 %.

Diagnostic performances of nCLE for the characterization of pancreatic masses are presented in Table 1.

Abstract number: P0838

Final diagnosis	n	Sensitivity		Specificity		PPV		NPV		Accuracy
		Group 1	Group 2	Group 1	Group 2	Group 1	Group 2	Group 1	Group 2	Group 1	Group 2
Adenocarcinoma	23	86%	78%	100%	100%	100%	100%	79%	67%	91%	85%
Neuroendocine neoplasm	3	100%	100%	93%	97%	60%	75%	100%	100%	94%	97%
Chronic Calcifying Pancreatitis	5	67%	40%	100%	100%	100%	100%	93%	90%	94%	91%

Conclusion: These two validations, even preliminary due to the small number of inclusions, show a really slight difference between experts and less trained physicians: the learning curve seems to be short.

Although the sensitivity still needs to be improved (by an additional work on the criteria), the excellent specificity of nCLE for the characterization of pancreatic masses could be very usefull tu rull out malignancy and avoid repeated diagnosis procedures.

Disclosure of Interest: None declared

P0839 PERFORMANCE OF LINEAR-ENDOSCOPIC ULTRASONOGRAPHY FOR LOCOREGIONAL EVALUATION OF AMPULLARY LESIONS

M. C. Petrone¹, E. Dabizzi¹, S. G. G. Testoni¹, V. Occhipinti¹, C. Doglioni², G. Balzano³, P. G. Arcidiacono¹

¹Gastroenterology and Digestive Endoscopy Unit, ²Pathology Unit, ³Pancreas Unit, Department of Surgery, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milano, Italy

Contact E-mail Address: petrone.mariachiara@hsr.it

Introduction: Accurate preoperative staging for ampullary neoplasm is mandatory for making therapeutic decisions. Endoscopic Ultrasound (EUS) has been suggested as the modality of choice in the locoregional staging of the ampullary lesions, because the high frequency ultrasound transducer probe can be placed in close proximity to the ampullary region. To date, almost all information available on staging of ampullary tumors has been obtained with radial echoendoscope, that is considered the gold standard.

Aims & Methods: Aim of the study was to compare the accuracy of linear array echoendoscope in locoregional staging of ampullary lesions, with histology and surgical pathology as gold standard. The Endoscopy Database of a tertiary referral center was reviewed, searching for patients referred for an evaluation in known or suspected ampullary lesion between January 2010 and January 2015. Patients demographic and clinical data were collected, including the lesion size and local tissue invasion. Histology from endoscopic and surgical specimens was assumed as reference standard. All EUS were performed by 3 experienced endosonographers by using linear array echoendoscopes (Pentax EG3870UTK). Data were analyzed using descriptive statistics.

Results: We identified 89 patients who underwent EUS for ampullary lesions. Among them, 48 pts were excluded (41/48 underwent EUS, without any treatment and in 7/48 histology did not confirm the suspected diagnosis). 41 pts (22 M; mean age 70.7 years± 12.1) were included in the study (5 pts previously treated with biliary stent). The mean size of the lesions was 15.9 ±7.5 mm. 23 patients (56%) were treated with whipple resection, 15 patients (37%) underwent endoscopic papillectomy, and 3 (7%) surgical papillectomy. Pathologic type of the tumors were adenoma in 18 pts (44%), adenocarcinoma in 23 pts (56%). In those undergoing endoscopic/surgical papillectomy, 16 had adenoma (89%), and 2 had adenocarcinoma (11%). Of the patients who underwent whipple resection 2 had adenoma (9%), 21 had adenocarcinoma (91%). For the assessment of local tissue invasion, the overall accuracy of EUS was 75.6% by using histology as the reference standard. Excluding pts with biliary stent, accuracy raised up to 81.1%. The diagnostic accuracy of EUS was 85.7%, 55.6%, and 80% in identifying patients with T1, T2, T3-4 stages, respectively. Overstaging by EUS occurred in 5 patients (12%), 3 of them had biliary stent. Understaging occurred in 2 patients (5%).

Conclusion: Linear EUS accurately predicts the depth of invasion in the preoperative evaluation of ampullary lesions, providing useful information for making therapeutic decisions, especially in selection of eligible patients for endoscopic treatment.

Disclosure of Interest: None declared

P0840 FINE NEEDLE ASPIRATION OF PANCREATIC CYSTIC LESIONS: A MULTICENTER, RANDOMIZED STUDY COMPARING STANDARD AND FLEXIBLE NITINOL NEEDLES

M. Wallace¹, M. Al-Haddad², W. Brugge³, S. Lakhtakia⁴, Z.-S. Li⁵, A. Sethi⁶, D. Pleskow⁷, C. Nguyen⁸, R. Pannala⁸, J. DeWitt², M. Raimondo¹, T. Woodward¹, M. Ramchandani⁴, Z. Jin⁵, C. Xu⁵, D. Faigel⁸

¹Mayo Clinic Jacksonville, Jacksonville, ²Indiana University, Indianapolis, ³Massachusetts General Hospital, Boston, United States, ⁴Asian Institute of Gastroenterology, Hyderabad, India, ⁵Changhai Hospital, Shanghai, China, ⁶Columbia Presbyterian, New York, ⁷Beth Israel Deaconess Hospital, Boston, ⁸Mayo Clinic Arizona, Scottsdale, United States

Contact E-mail Address: Wallace.Michael@mayo.edu

Introduction: Endoscopic ultrasound fine needle aspiration (EUS-FNA) is the reference standard for pancreatic cystic lesions (PCLs) diagnosis. Limited fluid aspirate can restrict analysis. A new nitinol 19G flexible (19G Flex) needle may improve access and aspiration, especially for viscous and/ or difficult to reach PCLs.

Aims & Methods: Document impact of needle gauge and flexibility on success of PCL aspiration and sufficient yield for cytology and CEA. Prospective multinational trial of 250 patients (pts) with PCLs ≥ 13mm at largest axis. Interim report on ITT basis for 125 pts with 30 day follow up. Pts randomized in 2:1:1 ratio to 19G Flex:19G:22G needles. Salvage with another needle if no access or incomplete aspiration. Primary endpoint: percent (%) total cyst volume aspirated based on pre- and post-aspiration PCL measurements. Other endpoints: successful EUS-FNA (complete aspiration/ fluid sufficient for testing), salvage rate, 30 day adverse events.

Results: 125 pts (mean age 67, 43% male, 30% symptomatic) treated with 19G Flex(62), 19G(32), or 22G(31) needles. PCLs: mean largest diameter: 22.6 ± 13.1mm; head 43%, body 22%, tail 31%; unilocular: 61% (76). Mean # passes all procedures including salvage: 1.1 ± 0.5. Mean % aspirated volume: 78 ± 38% (124). Successful EUS-FNA: 93.5% (116/124); performance of all needles was equivalent. Primary endpoint for 76 pts with unilocular PCLs by location and viscosity (Table 1) illustrates % aspirated volume for viscous PCLs in head of pancreas of 85% (19G Flex), 63% (19G std) and 66% (22G std) with enrollment ongoing. Salvage required in 13.6% (17/125) pts including 14 (82.4%) in head or very viscous PCLs. 19G Flex required fewer rescues compared to other needles: 9.7% (6/62)-19G Flex, 18.8% (6/32)-19G, and 16.1% (5/31)-22G needles. Complications in 7pts (6%): 1 bleeding PCL that refilled with blood (22G), 1 abdominal pain (19G), 3 acute pancreatitis (2-19G Flex, 1-22G), 2 unrelated deaths from metastatic endometrial (19G Flex) and neuroendocrine (22G) cancer.

Abstract number: P0840 Table 1.

Percent aspirated unilocular PCL volume by needle type

	19G Flex	19G	22G	Total	19G Flex-22G	19G-22G
	Mean ± SD(N)				P-value
Overall	86.9 ± 28.7(34)	80.0 ± 39.2(24)	79.3 ± 38.4(18)	82.9 ± 34.4(76)	0.453	0.946
Location
B/T	91.3 ± 20.1(21)	94.7 ± 18.7(14)	83.4 ± 34.5(11)	90.4 ± 23.7(46)	0.380	0.248
H/U	79.8 ± 38.8(13)	59.4 ± 51.2(10)	72.8 ± 45.9(7)	71.4 ± 44.2(30)	0.741	0.551
Viscosity
LW/SV	83.6 ± 31.5(27)	94.0 ± 23.5(18)	92.2 ± 25.4(12)	88.7 ± 27.9(57)	0.378	0.862
VV	99.8 ± 0.5(7)	38.0 ± 48.7(6)	53.4 ± 48.8(6)	65.6 ± 45.6(19)	0.046	0.497
Location & Viscosity
B/T & NV	88.7 ± 22.6(16)	99.8 ± 0.7(11)	99.6 ± 0.7(7)	94.5 ± 16.2(34)	0.136	0.976
H/U or VV	85.3 ± 33.9(18)	63.3 ± 47.8(13)	66.4 ± 45.1(11)	73.5 ± 41.8(42)	0.240	0.856

Location: B=body, T=tail, H=head, U=uncinate; Viscosity: LW=like water, SV=somewhat viscous, VV=very viscous, NV=non viscous

Conclusion: Results suggest that nitinol 19G flexible FNA needles may require fewer salvage procedures and show a trend of higher fractional cyst aspiration compared to standard needles for very viscous PCLs. Further data are forthcoming.

Disclosure of Interest: M. Wallace Conflict with: Study funded by Boston Scientific Corporation, M. Al-Haddad Consultancy: Boston Scientific Corporation, W. Brugge: None declared, S. Lakhtakia: None declared, Z.-S. Li: None declared, A. Sethi Consultancy: Boston Scientific Corporation, D. Pleskow: None declared, C. Nguyen: None declared, R. Pannala: None declared, J. DeWitt: None declared, M. Raimondo: None declared, T. Woodward: None declared, M. Ramchandani: None declared, Z. Jin: None declared, C. Xu: None declared, D. Faigel: None declared

P0841 VARIATIONS IN DIAGNOSTIC ACCURACY OF RADIAL AND LINEAR ENDOSCOPIC ULTRASOUND (EUS) FOR SUSPECTED CHOLEDOCHOLITHIASIS ARE RELATED TO CLINICAL PRESENTATION AND NOT TO TIME TO ERCP OR CHOLEDOCHOLITHIASIS RISK LEVEL

N. Barsic¹, T. Pavic¹, D. Hrabar¹, I. Budimir¹, M. Nikolic¹, N. Ljubicic¹

¹Sestre Milosrdnice University Hospital Center, Zagreb School of Medicine, Zagreb, Croatia

Contact E-mail Address: neven.barsic@gmail.com

Introduction: EUS is considered a reliable method in assessment of choledocholithiasis, but reported diagnostic accuracy rates vary, and patient numbers are not very large in the majority of reports. Given the high occurrence of suspected choledocholithiasis seen in daily practice and use of an invasive method (ERCP) in those with positive EUS findings, implications of inaccurate diagnosis are medically, financially and organizationally significant.

Aims & Methods: Our aim was to evaluate diagnostic accuracy of EUS in our setting with a large emergency department and very frequent cases of biliary lithiasis complications, and to compare the accuracy across different clinical scenarios and ASGE choledocholithiasis risk levels, as well as its dependence on time elapsed between EUS and ERCP and type of EUS probe used (radial vs. linear).

We retrospectively included 194 consecutive patients who underwent EUS for suspected choledocholithiasis in the period of two years (2011 and 2012). Mechanical radial (n=149) and linear (n=45) Olympus probes were used for EUS examination in all patients.

We compared the positive EUS findings with subsequently performed ERCP, and in patients with negative EUS we confirmed the lack of later biliary events at a 6-month follow-up visit and through electronic medical records revision. Comparison of accuracy was made between different clinical presentations, ASGE choledocholithiasis risk levels, time elapsed between EUS and ERCP and probe type.

Results: 106/194 (54.6%) of patients had a positive EUS finding of choledocholithiasis, and positive predictive value when compared to ERCP was 88.5% (85/96). There were no differences in accuracy with ASGE choledocholithiasis risk levels (6/11 pts with a false positive finding were ASGE high risk level) or type of EUS probe used (PPV with linear 92% vs. radial 87.3%). Time elapsed to ERCP was only slightly longer in pts with a false positive finding (mean 3.87 vs. 2.71 days).

However, significant difference was observed when comparing PPV in pts presenting with biliary colic or pancreatitis (PPV 72.0 %, n=18/25) and pts presenting with either cholangitis, obstructive jaundice or asympthomatic biliary dilatation or elevated liver enzymes (PPV 97.1 %, n= 67/69, P=0.0011).

In 88 patients with negative EUS findings, there were only 3 cases of biliary complications during follow-up, and neither of them underwent recommended cholecystectomy after the initial event, so negative predictive value of EUS would at worst be 96.6%.

Conclusion: Although generally high, different levels of diagnostic accuracy of EUS for choledocholithiasis reported in various studies could well be influenced by a difference in distribution of clinical presentations of patients studied.

This is probably the result of a transitory nature of biliary obstruction (due to a spontaneous propulsion of the stone), which is very frequent in settings of biliary colic and biliary pancreatitis, whereas obstructive jaundice and cholangitis are related to a more persistent CBD obstruction.

Disclosure of Interest: None declared

P0842 NATURAL HISTORY OF ASYMPTOMATIC UNIQUE PANCREATIC CYSTIC TUMORS CONSIDERED OF BENIGN POTENTIAL IN ENDOSCOPIC ULTRASOUND LONG-TERM SURVEILLANCE OF 144 PATIENTS

O. Luna¹,*, I. Oria¹, R. Gincul², C. Lefort¹, B. Pujol¹, J.-Y. Scoazec³, J.-C. Souquet⁴, J. A. Chayvialle², B. Napoleon¹

¹hopital prive Jean Mermoz, ²Ed Herriot Hospital, Lyon, ³Gustave Roussy, Villejuif, ⁴Croix Rousse Hospital, Lyon, France

Contact E-mail Address: oliluna@terra.com.br

Introduction: A follow up (FU) can be proposed for asymptomatic pancreatic cystic tumors with benignpotential (BCT) such as serous cystadenomas (SC) or congenital cysts. However, it is often difficult to confirm the diagnosis of BCT.In 1991,we proposed the criterias of BCT in endoscopic ultrasound (EUS).

Aims & Methods

Aim: Evaluatethe natural history of asymptomatic pancreatic cystic tumors considered as BCT by EUS. Between June 1992 and November 1996, 144 asymptomatic patients with suspected single BCT by the EUS were included. The exclusion criteria: acute or chronic pancreatitis; criteria for malignant potential in the EUS (wall thickening,echogenic fluid,mass syndrome,duct communication,unilocular cyst > 3 cm); multiple cysts. 111 women with a mean age of 60 years.EUS found in 101 cases a cyst multilocular(probable SC). In 43 cases,one cyst unilocular ≤ 3 cm. Cysts had an average diameter of 21 mm, a localization body-tail in 49. Clinical and radiological FU was recommended. Patients and physicians were recontacted every 5 years. Thelast assessment has been in September 2014.

Results: 4 patients (3%)were lost to FU. 21 patients (15%) underwent surgery,7 immediately (5 SC,1 Brunerienne,1 inconclusive) and 14 in FU due to the appearance of symptoms (1 SC),an increase in size or appearance of suspicious signs (8 SC,5 mucinouscystadenoma with one degenerated).47 patients (33%) died during the FU (mean 7 years).2 patients died of pancreatic pathology (1 neuroendocrine tumor,1 cystadenocarcinoma),42 died for a cause independent of the pancreas,3 died of unknown cause.4 patients had other cysts appearing (IPMN probably).54 patients are alive in October 2014 asymptomatic (mean 20 years).18 were a partial FU (mean 10 years). For these 72 patients (50%) the diagnosis of IPMN was mentioned 12 times before.4 cases the signs for a MC have occurred in older patients for surgery too.The mucinous lesions accounted for 18% of patients and were distributed between lesion initially unilocular (n=9/43:21%) or with microcysts (n=17/101:17%).

Conclusion: In this follow-up study in the very long term (20 years) EUS criteria had an accuracy of 82% for the diagnosis of BCT.One death related to pancreatic tumour was noted.18% of patients ultimately had mucinous cysts with malignant potential to justify the creation of more specific tests for BCT diagnosis.

Disclosure of Interest: None declared

P0843 IS ASCITES A CONTRA-INDICATION TO AN ENDOSCOPIC ULTRASOUND-GUIDED BILIARY DRAINAGE IN CASE OF UNSUCCESSFUL CATHETERIZATION?: RESULTS OF A PILOT STUDY

O. Luna¹, I. Oria¹, F. Fumex¹, J. Marsot¹, C. Lefort¹, V. Lépilliez¹, J. Balique¹, R. Bourdariat¹, S. Gaetan¹, B. Napoleon¹

¹Hopital Prive Jean Mermoz, Lyon, France

Contact E-mail Address: oliluna@terra.com.br

Introduction: In case of malignant obstruction of the bile duct with failure of endoscopic retrogradecholangiography (ERCP), a percutaneous trans-hepatic biliary drainage (PTBD) is usually done.One contra-indication of this procedure is the presence of ascites.Endoscopic ultrasound-guided biliary drainage (EUS-BD) could be a solution but it has never been evaluated in this situation.The objective of this single-center study is to determinewhether ascites is a contra-indication for EUS-BD.

Aims & Methods: Between July 2010 and July 2014 patients with choledocoduodenostomy (CD) or hepaticogastrostomy (HG) for an ERCP failure were included. Systematic bile samples for bateriology were performed at the time of puncture.October 2014 a retrospective analysis was performed comparing those with ascites (group 1) to those without ascites (group 2). The technical and clinical success, complications andfollow-up until death were compared between the two groups.

Results: 31 patients included.Group 1(5CD, 6HG) technical success in 10/11 cases.One complication (migration of the stent). Clinical success in 7/10 patients.4 patients died in the first month. One death related to the procedure. Bacteriology of the biliary fluid positive twice (22%). All patients died of disease progression (mean survival 78 days). Group 2 (8CD,12HG) technical success in 17/20 cases. Three complications (1 perforation, 1 bile peritonitis, 1 bleeding). Clinical success in 16/17 cases. Bacteriology of the biliary fluid positive in four cases. One patient had cholangitis. 14 patients died of disease (mean 115 days, 6 alive (mean 300 days).

Conclusion: This study showsthat we can achieve a EUS-BD with good technical efficacy in patients with ascites.The risk of infection remains limited (22% of patients) and comparable to patients without ascites.These results suggest aprospective multicenter study.

Disclosure of Interest: None declared

P0844 AN ALTERNATIVE METHOD OF DRAINAGE OF PSEUDOCYSTS IN PRESENCE OF BIG VARICES IN THE FUNDUS

P. N. Desai¹

¹Endoscopy, Surat Institute Of Digestive Sciences, Surat, India

Contact E-mail Address: drp_desai@hotmail.com

Introduction: An alternative method of drainage of Pseudocysts in presence of big varices in the fundus.

Aims & Methods

Aims: A study 18 cases of draining pseudocysts complicated by portal hypertension and gastric varices with EUS guided locating the site of puncture distally on the bulge.

Methods: 18 cases from all that were referred to us from 1^st January 2011 to May 30, 2014 with pseudocysts were found to be complicated with fundic and esophageal varcies secondary to splenic vein. UES revealed big varices around the GE junction and the proximal body and no window was found for EUS guided cyst drainage in the conventional manner. The bulge of the cyst was followed distally with an EUS scope and an area devoid of varices was found distally. Here the tip of the EUS scope was fully up and it was impossible to get a 19G needle out for puncture and further steps of conventional cyst drainage. Ttherefore we marked the area with biopsy forcpes taking a pinch of tissue for identification on passage of the side viewing scope subsequently. A conventional ERCP 4.2mm channel scope from Olympus was then passed, positioned in front of the marked area and the cyst punctured around the mark with a needle knife papillotome from Boston and guide wire placed under fluoroscopic control. The tract was then dilated with a 6.5Fr cystotome from Endoflex and dilated with a CRE balloon upto 12mm only to avoid bleeding. Two 10 Fr Double pig tail stents were kept. In cases with necrosis and additional naso cystic catheter was placed for lavage which was removed after 48 to 72 hours exchanging it for an additional 10Fr DPT stent. ERCP done if a leak was suspected at the time of removal of naso cystic drain and stent placed. Stents were removed after six weeks to three months and the PD stent removed or changed as needed.

Results:

Bulge Present	18	100.%
Puncture Possible around marked site	17	94.4%
Bleeding ( Minor )	3	16.7%
Necrosis Present	5	27.7%
Infected Fluid	4	22.2%
Naso Cystic Drain kept	9	50%
Perforation	0	0
Sepsis	4	22.2%
ERCP Performed	6	33.3%
Cysto gastrostomy stents Removed	12	63.1%
Stents still present	4	22.2%
Lost to Follow up	2	11.1%
Procedure Related Mortality	0	0

The bleeding was minor from the wall and was treated with injection of adrenaline and balloon tamponade.

The sepsis was treated with antibiotics for 5 to 7 days and was seen in patients with necrosis and infected fluid.

4 patients had a disrupted duct and hence the stents have not been removed.

Conclusion: In difficult situations of pseudocysts complicated with varices, puncturing distally on the bulge at a site marked by EUS scope is a feasible alternative. EUS guide drainage is difficult in these situations as the scope is angled acutely and this makes the procedure very difficult. The complications rates are also reasonable.

Disclosure of Interest: None declared

P0845 GLOBAL ASSESSMENT OF EUS PERFORMANCE SKILLS (GEUSP) - A NEW TOOL AND APPROACH TO OBJECTIFY AND MEASURE THE LEARNING CURVE AND TECHNICAL SKILLS OF ENDOSONOGRAPHISTS

P. Hedenström¹, B. Lindkvist¹, R. Sadik¹

¹Departement of Internal Medicine, Division of gastroenterology, Göteborg, Sweden

Contact E-mail Address: per.hedenstrom@vgregion.se

Introduction: The overall learning curve of endoscopic ultrasound (EUS) is regarded long, but until now it is not very well characterized in the literature. There is also a lack of easy to use tools to assess the practical skills of endosonographists in training.

Aims & Methods: The aim of this study was to elaborate and validate a new tool for the assessment of endosonographists in training and by this elucidate the learning curve of EUS.

The study was conducted at a tertiary university endoscopy center in West Sweden. Patients undergoing EUS for clinical reasons were enrolled and examined first by an endosonographist in training (performer) and secondly by an experienced endosonographist (observer). Both doctors performed EUS-guided puncture if this procedure was indicated. The observer assessed and scored 5 different parameters of the performer’s EUS-procedure, each on a 5-graded scale. A study specific assessment sheet, GEUSP, was designed for this purpose. The performer also scored him- or herself regarding the same 5 parameters including an aspect on confidence in own performance. Previous endoscopy experience including EUS and annual endoscopy volumes of the performer were registered. The overall GEUSP score was calculated regarding each case to assess the performer´s development over time. The influence of different variables on the GEUSP score was analyzed using non-parametric tests.

Results: During May 2014 – February 2015 a total of 60 patients (38 males and 22 females) were examined and four performers were assessed according to GEUSP. Two performers performed the majority of examinations (P1=48, P2=10, P3=1, P2=1) all were assessed by one single observer. EUS-FNA/FNB was performed by the performer in 22 cases. Target organs were as followed: Pancreas (29), Submucosal lesions (22), Paraintestinal lesions (11). There was a good correlation between the overall mean GEUSP-score of the observer and that of the performer (r = 0.68, p < 0.001) supporting the robustness of the assessment sheet. Analyzing comparable lesions there was a correlation between the overall mean GEUSP-score and the previous overall EUS experience of four performers assessed so far (r = 0.9, p=0.06). The observer´s mean overall GEUSP Score of Performer 1 was significantly higher after initial first 25 examinations, (3.7 vs 3.1, p < 0.01). There was no significant difference in the overall GEUSP score comparing different target organs nor comapring solid and cystic lesions. The assessment sheet was easy to use and the registration engaged few minutes. We did not notice any negative influence on the everyday endoscopy program due to the use of GEUSP. Two patients reported brief abdominal symptoms the day after EUS, but no certain complications related to EUS were verified during follow-up.

Conclusion: A new tool for the assessment of endosonographists in training (GEUSP) has been proven feasible and simple to use in clinical practice. Further evaluation of a larger cohort of endosonographists is ongoing. We invite other centers to participate in this study.

Disclosure of Interest: None declared

P0846 DIAGNOSTIC EFFICACY OF ENDOSCOPIC ULTRASOUND-GUIDED NEEDLE SAMPLING FOR UPPER GASTROINTESTINAL SUBEPITHELIAL LESIONS: A META-ANALYSIS

Q.-L. Li¹, P.-H. Zhou¹

¹Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China

Contact E-mail Address: zhou.pinghong@zs-hospital.sh.cn

Introduction: An increasing number of studies have been conducted on the use of endoscopic ultrasound (EUS)-guided needle sampling, including fine needle aspiration, fine needle biopsy, and trucut needle biopsy, for upper gastrointestinal (GI) subepithelial lesions (SEL). However, reported diagnostic efficacy varies greatly.

Aims & Methods: We did a meta-analysis to summarize up current evidences on diagnostic efficacy of EUS-guided needle sampling for upper GI SEL. A reproducible strategy was used to search four databases. 17 studies, including a total of 978 sampling attempts, were included in the final analysis. The primary outcome was the pooled efficacy of EUS guided needle sampling in upper GI SEL. Secondary outcomes were procedure-related complications, diagnostic errors, and independent factors related to a higher success rate.

Results: The pooled diagnostic rate of EUS-guided needle sampling was 59.9%, with a heterogeneity I² of 55.2%. Subgroup analysis and meta-regression suggested that the cell block method might be correlated with a higher diagnostic rate. Few severe complications were reported. Diagnosis errors were rare.

Conclusion: EUS guided needle sampling is a safe, but only moderately effective method for pathological diagnosis of upper GI SEL. However, the results have inherent limitations, especially in view of the limited sample size and heterogeneity of the original studies.

Disclosure of Interest: None declared

P0847 LONG-TERM REBLEEDING RISK AFTER ENDOSCOPIC THERAPY OF SMALL-BOWEL VASCULAR LESIONS WITH DEEP ENTEROSCOPY

A. Ponte¹, R. Pinho², A. Rodrigues¹, T. Pinto-Pais¹, C. Fernandes¹, I. Ribeiro¹, J. Silva¹, J. Rodrigues¹, M. Mascarenhas-Saraiva³, J. Carvalho¹

¹Gastroenterology, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, ²Gastroenterology, Centro Hospitalar Vila Nova de Gaia/Espinho, ManopH e ManopH-Instituto Cuf, Vila Nova Gaia, Porto, ³Gastroenterology, ManopH e ManopH-Instituto Cuf, Porto, Portugal

Contact E-mail Address: ana.ilponte@gmail.com

Introduction: In western countries, small-bowel vascular lesions (SBVL) represent the most frequent small bowel finding in patients with obscure gastrointestinal bleeding (OGIB).¹ Recent systematic reviews raise some doubts concerning the therapeutic efficacy of Balloon-Assisted Enteroscopy (BAE) of SBVL after 2y of follow-up and there is limited data regarding the long-term outcome of these patients.^2,3 Objective: Evaluate the short- and long-term rebleeding risk after BAE therapy of SBVL detected in capsule enteroscopy.

Aims & Methods: Between July 2007 and February 2015, all patients with SBVL who underwent BAE therapy were included. The endpoint was rebleeding, defined as the presence of overt OGIB, the need for red blood cells transfusions or a decrease in haemoglobin ≥2g/dL. Factors predictive of rebleeding were also analysed. Statistical analysis: Kaplan-Meier survival curves, Log-rank test, t-student test, X². Significance: p < 0.05.

Results: 35 patients with SBVL underwent BAE therapy, 57.1% were men with a mean age of 67.8+/-13.7 years. Findings included angioectasias in 97.1% (n=34), classified in types 1a in 14.3% (n=5) and 1b in 82.9% (n=29), and Dieulafoy’s lesion in 2.9% (n=1) classified as type 2a.⁴ Types 1a/1b were approached exclusively with argon plasma coagulation in 88.6% (n=31) or combined with other technique in 11.4% (n=3); and the type 2a lesion was treated with adrenaline and clips. Globally, rebleeding occurred in 40% (n=14) of cases, manifested as overt OGIB in 35.7% (n=5), need of blood transfusion in 42.9% (n=6) and haemoglobin drop ≥2g/dL in 21.4% (n=3). Rebleeding at 1y/2y/3y/4y/5y after BAE therapy occurred in 32.7%/38.3%/46.0%/53.7%/63.0%, respectively. Patients with aortic stenosis/chronic renal failure/cirrhosis/Osler-Weber-Rendu syndrome had a rebleeding risk at 2y/3y after BAE therapy of 51.3/67.6%, superior to those without these comorbidities (22.2/22.2%), p=0.006.

Conclusion: Rebleeding at 2y after BAE therapy of SBVL occurred in 38.2%, consistent with two recent systematic reviews which revealed a rebleeding rate of 45% at 26 months and 42.7% at 1.5-2y.^2,3 Long-term risk of rebleeding progressively increases, reaching 63% at 5y after BAE therapy. The presence of comorbidities increases the rebleeding risk.

Disclosure of Interest: None declared

P0848 SMALL-BOWEL SURVEILLANCE IN PATIENTS WITH PEUTZ-JEGHERS SYNDROME: COMPARING MAGNETIC RESONANCE ENTEROCLYSIS AND DOUBLE BALLOON ENTEROSCOPY

A. Goverde¹², A. Wagner¹, S. E. Korsse², M. E. Van Leerdam²³, N. Krak⁴, J. Stoker⁵, H. Van Buuren², R. M. Hofstra¹, M. J. Bruno², P. Dewint²⁶, E. Dekker⁷, M. Spaander²

¹Clinical Genetics, ²Gastroenterology & Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, ³Gastroenterology & Hepatology, Antoni van Leeuwenhoek Hospital, Netherlands Cancer Institute, Amsterdam, ⁴Radiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, ⁵Radiology, Academic Medical Center, Amsterdam, ⁶Gastroenterology & Hepatology, Maasstad Hospital Rotterdam, Rotterdam, ⁷Gastroenterology & Hepatology, Academic Medical Center, Amsterdam, Netherlands

Contact E-mail Address: a.goverde.1@erasmusmc.nl

Introduction: Surveillance of the small-bowel with polypectomy of significant polyps (SP, defined as polyps ≥15mm in diameter) prevents polyp-related complications in Peutz-Jeghers syndrome (PJS). However, evidence for the optimal imaging technique for these patients is lacking. Therefore, we aimed to compare the diagnostic yield and patient preference of Magnetic Resonance Enteroclysis (MRE) and Double Balloon Enteroscopy (DBE) in PJS.

Aims & Methods: Adult PJS patients recruited from two academic centers underwent MRE followed by a proximal DBE with polypectomy of SP within 20 weeks. The endoscopists were blinded for the MRE results. DBE was performed under conscious sedation with midazolam and fentanyl intravenously or under general anaesthesia with propofol. We compared the number of SP and total number of polyps detected by MRE and DBE. Patients’ perception regarding shame, pain, burden and duration of both procedures were assessed through questionnaires, as well as their preference for future surveillance.

Results: Fifteen PJS patients, 67% males with a median age of 47 (IQR 39-53) years underwent both MRE and DBE. The median maximal insertion depth for DBE was 270cm (IQR 160-340cm). SP were identified by MRE and/or DBE in 12/15 (80%) patients. Agreement between MRE and DBE on the presence of SP was 87% (13/15) and both methods identified 11 patients with SP. Significantly more polyps were detected by DBE than with MRE (148 vs. 93, p=0.03), however there was no significant difference in the detection of SP (47 by DBE vs. 38 by MRE, p=0.37). Patients’ perception regarding shame and burden at preparation and during both procedures did not differ significantly between MRE and DBE. However, patients reported significantly more pain during the preparation for MRE than for DBE (moderate vs. no pain, p=0.02). Perception of pain during the procedures was comparable (both mild, p=0.89). Significantly more patients perceived a longer procedure time for MRE than for DBE (38.5% vs. 8.5%, p=0.05). For future small-bowel surveillance 10/13 (77%) patients preferred DBE over MRE (p=0.09).

Conclusion: Our results suggest that MRE and DBE have comparable diagnostic yield of clinically relevant polyps ≥15mm in diameter. Although DBE resulted in incomplete small-bowel visualization in all patients, it allows for direct intervention and was preferred over MRE by patients in this series. Based on the MRE results, 11/15 (73%) patients had an indication for DBE with polypectomy. Larger cohorts of PJS patients are needed to fully evaluate the diagnostic yield of DBE compared with other diagnostic modalities.

Disclosure of Interest: None declared

P0849 THE ROLE OF DOUBLE-BALLOON ENTEROSCOPY IN MALIGNANT SMALL BOWEL TUMORS MAY BE DECISIVE

E. Pérez-Cuadrado Robles¹, P. Esteban Delgado¹, B. Martinez Andrés¹, P. Bebia Conesa¹, J. L. Rodrigo Agudo¹, S. Chacón Martinez¹, E. Torrella¹, A. Lopez Higueras¹, J. Shanabo¹, E. Perez-Cuadrado Martinez¹

¹Gastroenterology, Morales Meseguer Hospital, Murcia, Spain

Contact E-mail Address: kikemurcia@gmail.com

Introduction: Malignant small bowel tumors (MSBT) are a heterogeneous and relatively rare group of neoplasms. Double balloon enteroscopy (DBE) role in these lesions remains controversial.

Aims & Methods: The aim of this study was to assess the DBE role in MSBT. The present retrospective study included all consecutive patients who underwent a DBE with final diagnosis of a malignant neoplasm from 2004 to 2014 in our referral center. Patient demographic and clinical pathological characteristics were reviewed. MSBT diagnosis was achieved either by DBE directed biopsy, endoscopic findings or histological analysis of surgical specimen. We have analyzed DBE impact in the outcome and clinical course of these patients.

Results: Of 627 patients, 28 (4.5%) (mean age: 60 ± 17.3 years) underwent 30 procedures (25 anterograde, 5 retrograde) and were diagnosed of a malignant tumor. Patients presented with obscure gastrointestinal bleeding (n = 19, 67.9%), occlusion syndrome (n = 7, 25%) and diarrhea (n = 1, 3.6%). They were diagnosed by DBE biopsy (n = 18, 64.3%), histological analysis of surgical specimen (n = 7, 25%) and unequivocal endoscopic findings (n = 2, 7.1%). Gastrointestinal stromal tumor (n = 8, 28.6%), adenocarcinoma (n = 7, 25%), lymphoma (n = 4, 14.3%), neuroendocrine tumor (n = 4, 14.3%), metastatic (n = 3, 10.7%) and Kaposi sarcoma (n = 1, 3.6%) were identified. In summary, DBE modified outcome in 7 cases (25%), delaying or avoiding emergency surgery (n = 3), modifying surgery approach (n = 2) and indicating emergency SB partial resection instead of elective approach (n = 2).

Conclusion: DBE may be critical in the management of MSBT providing additional information that may be decisive in the clinical course of these patients.

Disclosure of Interest: None declared

P0850 A PROSPECTIVE COMPARISON OF SAFETY AND TOLERABILITY OF PROPOFOL VERSUS STANDARD SEDATION FOR DOUBLE BALLOON ENTEROSCOPY - TIME FOR A PUSH FORWARD?

F. Branchi¹, D. Sanders², D. Turnbull³, G. Eapen³, S. Jankowski³, R. Sidhu²

¹Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy, ²Academic Department of Gastroenterology, ³Department of Anesthesiology, Royal Hallamshire Hospital, Sheffield, United Kingdom

Contact E-mail Address: federica.branchi@gmail.com

Introduction: Double balloon enteroscopy (DBE) is routinely performed with moderate sedation in the UK. However, in comparison to standard endoscopy, DBE is complex and takes longer, therefore deep sedation with propofol could improve tolerability and feasibility of the test.

Aims & Methods: All patients undergoing DBE between March13 and October14 were prospectively enrolled. DBE was performed either with administration of sedation with fentanyl and midazolam or with anesthetist-assisted deep sedation with propofol, the decision being made on the basis of patients’ clinical history and expected length of the test. Data from patients receiving propofol were compared to those from patients receiving standard sedation during the same period. Patients were asked to fill in a questionnaire regarding their expectations before the test and their satisfaction afterwards. Anxiety, pain and discomfort were assessed by means of validated numeric rating scales (NRS, range 0-10). Data on comorbidities, previous surgery and hospital anxiety and depression scores (HADS) were also collected. The procedural characteristics of DBE were assessed.

Results: Twenty-one DBE (18 oral, 3 anal, 33% male) were performed with the aid of propofol infusion and 67 (54 oral, 13 anal, 51% male) with standard sedation. Mean age was 48 ± 14.3 in the propofol group and 58.6 ± 15.9 in the sedation group (p=0.012). There were no other differences in demographics, comorbidities or HADS scores between the groups. The indications for DBE included obscure gastrointestinal bleeding (n=45), Peutz-Jeghers syndrome (9) and suspected Crohn’s disease (20), small bowel tumor (10) or celiac complication (2). The mean dose of propofol administered was 1123 ± 483 mg. The mean doses of midazolam and fentanyl were 6 ± 3 mg and 118 ± 54 mcg respectively. No differences were observed in terms of diagnostic yield (52% vs 57%, p=ns) and therapeutic yield (33% both groups). Patients in the propofol group reported lower scores of pain (median score 0, IQR 0-0.5 vs 3, IQR 0-6, p < 0.0001), discomfort (median 0, IQR 0-0.5 vs 3, IQR 1-7, p < 0.0001) and distress (median 0, IQR 0-0 vs 1, IQR 0-5, p=0.001) during the procedure. Whilst there were no complications in the propofol group, there was one episode of oxygen desaturation in the control group.

Conclusion: The use of propofol for DBE has a good safety profile and better patient tolerability and satisfaction in comparison with moderate sedation. It is associated with a high diagnostic and therapeutic yield. Its use should be recommended when the procedure is expected to be longer and technically challenging.

Disclosure of Interest: None declared

P0851 DOUBLE-BALLOON ENTEROSCOPY IN PATIENTS WITH CARDIOVASCULAR COMORBIDITIES - IS IT WORTH THE ‘CORONARY’?

F. Branchi¹, D. Sanders², R. Sidhu²

¹Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy, ²Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, United Kingdom

Contact E-mail Address: federica.branchi@gmail.com

Introduction: Double balloon enteroscopy (DBE) is an advanced endoscopic technique for the diagnosis and treatment of small bowel diseases. It is a relatively invasive and long procedure therefore its use in patients with comorbidity can be risky.

Aims & Methods: The aim of our study was to assess the safety and feasibility of DBE in patients with cardiovascular comorbidities.

All consecutive patients referred for DBE in our trust were prospectively reviewed. Clinical and demographic data were collected and patients with cardiovascular comorbidities were included in the analysis. Patients were divided into 2 groups- elderly (Group 1: age > 70 years) and the young (Group 2: age <70 years) Diagnostic and therapeutic yields, dose of sedation and complications rates were collected.

Results: Out of a total of 404 DBE procedures, 97 were performed in patients with one or more cardiovascular (CV) comorbidities (Group 1=52, group 2=45), including ischaemic heart disease (n=61), valvular replacement (n=24), atrial fibrillation (AF, n=19), chronic cardiac failure (CCF, n=16), arrhythmias with pacemaker implantation (n=5), previous cerebrovascular event (n=8). AF and CCF were commoner in the elderly compared to the young (p= 0.035 and p=0.026 respectively). There were no significant differences in warfarin or NSAIDS use in the two groups. The indications for DBE were obscure gastrointestinal bleeding (occult, 59%, and overt, 27%), suspected Crohn’s disease (7%), small bowel stricture at radiology (4%) and suspected celiac complication/malabsorption (3%). Transfusion was required in 67% patients in the elderly group and 60% in the younger group (p=ns). There were no differences in terms of procedure time between the elderly and the young (median time 70 minutes, range 35-125, vs 65, range 25-140, p=ns). Elderly patients were administered significantly lower doses of midazolam (median dose 4 mg, range 1.5-10 vs 6 mg, range 2-10, p < 0.0001) and fentanyl (median dose 50 mcg, range 12.5-100 vs 75, range 12.5-200, p < 0.0001).

DBE had high diagnostic (65% and 58%, p=ns) and therapeutic yield (54% vs 33%, p=ns) in both groups. The most common finding was angiodysplasia in both groups (48% vs 29%, p=0.06), other findings included ulcers (6% vs 9%), small bowel polyps (0% vs 7%) or tumors (0% vs 4%), diverticula (4% vs 0%), changes of celiac disease and intestinal lymphangectasia (0% vs 6%). The complication rate was 3% overall with one non STEMI in the elderly group and one episode of cardiac failure and a respiratory arrest in the younger group.

We also made comparisons between patients with CV comorbidity compared to all others without CV comorbidity undergoing DBE in the same period. The overall diagnostic yield was higher in patients with CV, irrespective of age, as compared to all other patients without CV comorbidity (62% vs 46%, p=0.005). Similarly, the therapeutic yield was also higher (44% vs 18%, p < 0.0001) in relation to the high number of vascular lesions treated in patients with CV comorbidity. The difference in complication rate between patients with and without CV comorbidities did not reach statistical significance (3% vs 1%, p=0.15).

Conclusion: We are the first to demonstrate that DBE in patients with CV comorbidity is relatively safe and with a good diagnostic and therapeutic yield. Careful patient selection is imperative to prevent serious complications.

Disclosure of Interest: None declared

P0852 THE OVER-THE-SCOPE-CLIP (OTSC) AS A THERAPEUTIC OPTION FOR IATROGENIC PERFORATION (IP), ANASTOMOTIC LEAKAGE (AL) AND CHRONIC FISTULA (CF) IN THE GASTROINTESTINAL TRACT

J. Stückle¹, J. Brueckner¹, A. Probst¹, M. Bittinger¹, A. Ebigbo¹, H. Messmann¹, S. Goelder¹

¹Department of Internal Medicine III, Klinkum Augsburg, Augsburg, Germany

Contact E-mail Address: johannes.stueckle@klinikum-augsburg.de

Introduction: Patients with iatrogenic perforation during endoscopy, anastomotic leakage and chronic fistula used to be transferred to the surgeon for further therapy. Since the recent development of the Over-The-Scope-Clip (OTSC), an increasing number of such lesions can be treated endoscopically which makes the closing procedure to a fast and safe method.

Aims & Methods: All applications of OTSC in our department between 12/2009 and 02/2015 were assessed prospectively and classified into three groups: 1. iatrogenic perforation (IP) during endoscopy, 2. anastomotic leakage (AL) after upper, middle or lower gastrointestinal surgery and 3. chronic gastrointestinal fistula (CF). Technical success was determined by the endoscopist subsequently to the procedure. As a second end point, we assessed the clinical success. Additionally, we added all cases of further interventional or surgical treatment All additionally required interventions (e.g. interventional radiology or surgery) were documented.

Results: n = 34 patients (m = 20, f = 14; mean age 70 years, range 30-89) underwent OTSC-treatment and were classified by indication:

1. IP (n = 10): The perforations were caused by piece-meal resection of an duodenal (4) or antral (1) adenoma, endoscopic retrograde cholangiopancreatography (2), diagnostic colonoscopy (2) and accidental perforation of an endosonographic fine-needle biopsy (1).

None of the patients needed to be transferred for surgical treatment. One patient (10 %) showed an insufficient closure but could be treated conservatively by means of a drainage of a retroperitoneal abscess. All patients survived with an excellent outcome.

2. AL (n = 15): OTSC clipping was performed due to anastomotic leakage in different surgery sides of the upper, middle and lower gastrointestinal tract: Gastric anastomosic leakage in bariatric surgery (2), duodenal leakage after pancreas- or aorta-surgery and cholecystectomy (3), leakage after esophageal (5) and colonic surgery (5). Technical success was achieved in 100% of these interventions. However, 6 patients (40 %) did not experience sufficient clinical amerlioration. The reason for these failure were additional developed leakage and persisting leakage. Further interventional and surgical treatment was needed.

3. CF (n = 9): Persisting leakage after removal of an infected percutanous endoscopic gastrostomy (1), intestinale fistulae due to acute-necrotising panceatitis (2), chronic enterocutanous fistula (1), rectovaginal fistula after radiation therapy (1), perforating nasojejunal tube (1), spontaneously perforated gastric ulcer (1) and colonic perforation of unknown reason (2). All 9 patients could be successfully treated by endoscopic closing with the OTSC primarily. However, 7 patients (77.8%) developed a relapse of fistula or new fistula were arisen. Endoscopic treatment failed in these cases.

Conclusion: All iatrogenic perforations were sufficiently closed by OTSC and showed an excellent technical and clinical outcome without any further surgical treatment required. However, anastomotic leakage and chronic fistula that are endoscopically closed by OTSC, often require additional interventional or surgical procedures.

Disclosure of Interest: None declared

P0853 HYPERAMYLASAEMIA AND ACUTE PANCREATITIS AFTER DOUBLE BALLOON ENTEROSCOPY: A PROSPECTIVE STUDY

M. F. Hale¹, D. S. Sanders¹, R. Sidhu¹

¹Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield, United Kingdom

Contact E-mail Address: melissa.hale@sth.nhs.uk

Introduction: Hyperamylasaemia and acute pancreatitis are potential complications following a double balloon enteroscopy (DBE) procedure. The mechanism of these complications is not fully understood. We present a prospective analysis of all patients undergoing DBE at a tertiary centre.

Aims & Methods: Single centre, prospective study involving all consecutive patients attending for DBE by either route, between 23rd Aug 2012 and 3rd October 2014. Serum amylase levels were obtained before and three hours after the procedure. Clinical evaluation for signs and symptoms of pancreatitis was performed three hours after the procedure. A record of the procedure duration, insertion depth and number of passes was also documented. Hyperamylasaemia was defined as an elevation of the serum amylase level to greater than the upper limit of normal.

Results: 115 procedures were performed on 89 patients, mean age 57.4 years (21-83 years), 46 male (51.7%). Indication for procedure is presented in Table 1. 91 procedures were performed per orally and 24 via the anal route. 88 procedures were performed on the basis of a positive small bowel capsule endoscopy (SBCE), 9 patients did not have prior SBCE due to failure to excrete the patency capsule. Indication for DBE is presented in Table 1. Overall 47 patients (61%) had an elevated serum amylase post procedure. Hyperamylasaemia post-procedure was observed in significantly more patients following per-oral DBE compared to DBE via the anal route (p=0.03). Hyperamylasaemia in the per-oral group was associated with procedure depth (mean 147cm vs 187cm p < 0.0009) and number of passes (mean 10 vs 18 p < 0.0007), but not procedure duration (mean 64 vs 70 mins p=0.2) or dose of fentanyl administered (mean 108mcg vs 118mcg p=0.6). No patients developed signs or symptoms of pancreatitis post-procedure.

Table 1.

INDICATION	No. of PATIENTS
Iron deficiency anaemia	46
Obscure gastrointestinal bleeding	19
Suspected Crohn’s	15
Peutz Jegher’s syndrome	11
Abnormal radiology	6
Small bowel stricture	6
Abdominal pain	4
Coeliac complications	3
Other	4

Conclusion: Hyperamylasaemia is common following DBE per-orally and is associated with procedure depth and number of passes. However, in the majority of cases this is of limited clinical significance and no patients in our series went on to develop pancreatitis.

Disclosure of Interest: None declared

P0854 MAGNIFYING NARROW-BAND IMAGING BY USING NEWLY DEVELOPED MAGNIFYING ENTEROSCOPY CAN BE USEFUL FOR EVALUATION OF INFLAMMATORY ACTIVITY IN SMALL INTESTINAL CROHN’S DISEASE: A PILOT STUDY

N. Ogata¹, K. Ohtsuka², S. Hayashi¹, M. Misawa¹, F. Ishida¹, S.-E. Kudo¹

¹Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, ²Enodoscopy unit, Tokyo Medical and Dental University Hospital, Tokyo, Japan

Contact E-mail Address: n.ogata@hotmail.co.jp

Introduction: The development of balloon endoscopy and capsule endoscopy has made observation of the small intestine possible in clinical practice. The usefulness of magnifying endoscopy has already been reported in observing the pharynx, esophagus, stomach and colon. The prototype of a single-balloon enteroscopy (SBE) with 80x magnification has been recently developed.

Aims & Methods: The aim of this pilot study was to assess the efficacy of narrow-band imaging (NBI) magnifying findings for evaluating the severity of inflammation in small intestinal crohn’s disease (CD). The study was conducted in Showa University Northern Yokohama Hospital. We included CD patients who underwent enteroscopy with magnification from September 2013 to December 2014. NBI images and a biopsy specimen were obtained from small intestinal mucosa for CD patients with use of SBE (Y-0007, Olympus, Tokyo). Magnifying NBI was performed, and the images were evaluated by assessing visibility, increased vascularization, and the increased caliber of capillaries into three grades as follows: Normal, Visible and Irregular. Normal was indicative of inactive disease, while Visible and Irregular were indicative of acute inflammation in our study. The outcome measures included the diagnostic ability of magnifying NBI findings to distinguish active CD from inactive CD on the basis of histological activity.

Results: Twenty-two patients were enrolled. There was a correlation between magnifying NBI findings and the histological assessment (Spearman’s |r| = 0.667).The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of magnifying NBI findings for diagnosing acute inflammation were 71.4%, 95.2%, 83.3%, 90.9%, and 89.3%, respectively.

Conclusion: The NBI magnifying findings in the small intestinal mucosa had a correlation with histological inflammation and could help in distinguishing between active and inactive in CD.

Disclosure of Interest: None declared

P0855 MULTICENTRE EXPERIENCE USING A NOVEL DEEP ENTEROSCOPY PLATFORM IN SURGICALLY ALTERED GASTROINTESTINAL ANATOMY

J. X. Cai¹, D. L. Diehl², A. Hoffman³, A. C. Storm¹, A. H. Tieu¹, M. H. El Zein¹, M. A. Khashab¹, R. Kiesslich³, P. I. Okolo III¹, V. Kumbhari¹

¹Division of Medicine, Department of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, ²Department of Gastroenterology and Nutrition, Geisinger Medical Center, Danville, United States, ³Department of Internal Medicine II, HSK Hospital, Wiesbaden, Germany

Contact E-mail Address: vkumbhari@gmail.com

Introduction: Conventional deep enteroscopy platforms achieve technical success rates between 61-98% in patients with surgucally altered anatomy. However, they lack widespread availability and have limited therapeutic potential due to a smaller working channel. Through-the-scope balloon-assisted enteroscopy (TTS-BAE) marketed as NaviAid AB (Smart Medical Systems Ltd., Ra’anana, Israel) is a novel technique using a standard adult colonoscope allowing for a broader range of interventions through the larger working channel but may be hampered by a shorter depth of maximal insertion.

Aims & Methods

Aims: to determine the efficacy and safety of TTS-BAE in patients with surgically altered anatomy.

Methods: A retrospective multicentre (2 in U.S., 1 in Germany) study of consecutive patients with sugrically altered anatomy who underwent TTS-BAE between 2012 to 2014 were included. Target success was defined as ability to access the intended target. Technical success was defined as completion of the procedure as intended. Clinical success was defined as >50% reduction in abdominal pain or hepatic enzyme levels and resolution of jaundice or bleeding. Adverse events were graded according to the ASGE lexicon’s severity grading system.

Results: A total of 42 patients (mean age 53yr, 18 female) underwent anterograde enteroscopies with a median procedure time of 42.5 minutes (25-250) (Table 1). Overall, the intended target was reached in 57.14% (n=24), of which 95.83% (n=23) were technically successful and 91.67% (n=22) were clinically successful. The biliopancreatic limb and deep small bowel had the highest rates of target and technical success (Table 1). Success rates did not differ between patients with RY vs not RY anatomy (P=0.78). A total of 7 metal stents and one 10Fr plastic stent were successfully deployed (5 biliary, 2 jejunal); this would not have been possible using other platforms. Adverse events occurred in 3 (7.14%) cases: aspiration pneumonia (mild), cholangitis (mild) and perforation (severe) distal to the HJ requiring surgical closure.

	N (%)	Target success (%)	Technical success (%)	Clinical success (%)
Type of anatomy
RYGB	8 (19.05)	62.5	62.5	62.5
Transplant RYHJ	7 (16.67)	57.14	57.14	57.14
Non-transplant RYHJ	12 (28.57)	50	41.67	41.67
Whipple	10 (23.81)	60	60	60
Other	5 (11.90)	60	60	40
Indication for TTS-BAE
ERCP	33 (78.57)	57.58	54.55	54.55
Small bowel stricture	5 (11.9)	80	80	60
GI bleeding	4 (9.52)	75	75	75
Target of TTS-BAE
Hepaticojejunostomy/ Jejunojejunostomy	32 (76.19)	56.25	56.25	56.25
Deep bowel	5 (11.9)	75	75	50
Biliopancreatic limb	4 (9.52)	50	25	25
Excluded stomach	1 (2.38)	0	0	0

Conclusion: TTS-BAE does not reach the therapeutic target as often as conventional platforms possibly due to its shorter depth of insertion and the less flexible adult colonoscope. However, we demonstrate very high technical and clinical success rates once an intended target is reached, which can be particularly useful for metal stent deployment.

Disclosure of Interest: J. Cai: None declared, D. Diehl: None declared, A. Hoffman: None declared, A. Storm: None declared, A. Tieu: None declared, M. El Zein: None declared, M. Khashab Financial support for research: Cook Medical, Consultancy: Boston Scientific, Olympus America, Xlumena, R. Kiesslich: None declared, P. Okolo III: None declared, V. Kumbhari: None declared

P0856 THE SMALL BOWEL VIDEOCAPSULE ENDOSCOPY: MAY WE DELEGATE IT TO NURSES ?

J. Dreanic¹, M. Gaudric¹, M. Dhooge¹, R. Coriat¹, S. Leblanc¹, F. Prat¹, V. Abitbol¹, E. Sion¹, V. Goncalves¹, C. Michel¹, D. Lalo¹, S. Chaussade¹

¹Gastroenterology and endoscopy unit, Hopital Cochin - APHP, Paris, France

Contact E-mail Address: johann.dreanic@cch.aphp.fr

Introduction: Small bowel videocapsule endoscopy (VCE) is a non-invasive and validated technique allowing the visualization of the small intestine mucosa. It generates more than 40,000 images per examination and induces a long median time of medical reading that may exceed one hour. In a transfer of skills’ program, Nurses (N) might be involved in the VCE reading. We herein present a feasibility study that evaluated two strategies of transfer skills of the VCE to N through either the pre-selection of abnormalities or the complete analysis.

Aims & Methods: Twenty VCE were selected and interpreted by two medical experts (group A). Two N with endoscopic experience were trained for the small bowel VCE reading. Pre-selection of VCEs’ pathological images were performed by N. Other experts in VCE readings established the definitive VCE’s report from pre-selected images (group B). Meanwhile, N produced a report of the VCE (group C). The stomach and small intestine transit times and the reading time were recorded. The accuracy of the whole VCE interpretation was compared (group A vs. B; A vs. C). Experts reviewed all discordant interpretations.

Results: The extent of transit time in the stomach and the small intestine, and the identification of a normal endoscopic examination were not statistically different between group A and group B. The accuracy of reports from group A and B was 95% (19/20). In one case, N has not selected the pathological image, corresponding to a duodenal ulcer. The VCE average reading time by the expert in the group B was significantly shorter than in the group A (9.2min +/- 0.5 vs. 34 +/- 9.9min; p<0.01). Time analysis was not statistically different between the groups A vs. C (34min +/- 9.9 vs. 4.1 +/- 34.1min; p=0.53). The accuracy of reports from group A and C was 80% (16/20). In 4 cases, proofreading revealed a discordant interpretation. The discrepancy was due to a lack of pathological images’ selection of the selected pictures for the final report (n = 2) and a lack of interpretation (n = 2) in group B.

Conclusion: In small bowel VCE interpretation, a pre-selection of pathological images by a trained N could be integrated in a transfer of skills’ program and appeared feasible. The average gain of time for the gastroenterologists is significant and up to 25 minutes per examination. Interestingly, an overall delegation of small bowel VCE interpretation from physicians to N remained not sufficient enough and deserved to be improved. Considering the medical time constrains, our study justifies evaluating in a larger study the delegation of the pre-selection images by N in a transfer of skills’ program.

Disclosure of Interest: None declared

P0857 HISTORICAL ANALYSIS OF SMALL BOWEL CAPSULE ENDOSCOPY PERFORMANCE IN A SPANISH TERTIARY HOSPITAL

J. Egea-Valenzuela¹, P. Tomas-Pujante¹, E. Iglesias-Jorquera¹, G. Carrilero-Zaragoza¹, F. J. Alvarez-Higueras¹, A. Pereñiguez-Lopez¹, E. Sanchez-Velasco¹, F. Alberca-de-las-Parras¹, F. Carballo-Alvarez¹

¹Digestive Diseases, Hospital Clinico Universitario Virgen de la Arrixaca, Murcia, Spain

Introduction: Capsule endoscopy (CE) is a widely extended technique for the diagnosis of small bowel pathology. In our hospital it has been available since 2004 with an increasing number of procedures along the time. At the beginning no more than some tens of studies were performed while up to 150 patients per year have come for CE in the last years.

Aims & Methods: Our aim is to analyze the data from our historical database of small bowel CE starting in year 2004.

We have retrospectively analyzed the data from the patients under small bowel CE in our hospital from October 2004 to April 2015, including demographic data, indications, findings and complications. Indications have been divided in: obscure occult gastrointestinal bleeding (OOcGIB), obscure overt gastrointestinal bleeding (OOvGIB), inflammatory bowel disease (IBD), and other indications (including polyposis, celiac disease, abnormal previous radiologic test, etc.). Findings in CE studies have been defined as: vascular ectasia (VE); ulcerative lesions (UL), including drug-induced lesions and Crohn’s disease; other lesions, such as polyps, submucosal tumors, atrophy, etc.; normal (no findings); and inconclusive studies due to gastric o enteric retentions, technical problems, poor bowel cleansing, etc.

Results: We have included 1027 CE studies, after exclusion of those with incomplete or indefinite information. The average age of the patients is 56.45 years old (4 - 91 y-o), including 471 men (57.55 y-o) and 556 women (55.54 y-o). The most frequent indication was OOcGIB (n=471, 214 men/257 women), followed by OOvGIB (n=240, 126 men/114 women), IBD (n=224, 94 men/130 women) and other indications (n=92). In TABLE 1 we show the distribution of the different indications according to sex and age.

The most frequent finding was VE (n=583), alone or with secondary findings. UL were observed in 329 cases, alone or with other lesions. Other kind of lesions as polyps or small bowel submucosal tumors were observed in 159 cases, in most of them as secondary or incidental findings.

It is remarkable that the greatest rate of normal studies occur in the group of IBD, probably related to the lack of evidence referring to factors associated to the diagnostic yield of CE in these cases and over-indication of the technique. On the other hand it is also striking the number of UL seen in patients presenting with OOvGIB, probably because many of them were under nonsteroidal anti-inflammatory drugs or antiplatelets.

No major complications have been observed in our database. 3 cases of gastric and 5 small bowel retentions of the capsule have been reported. All of them were managed conservatively, with no need for urgent surgery.

	OOcGIB	OOvGIB	IBD	Other indications
MEN	n = 214	n = 126	n = 94	n = 41
	Age: 65.2	Age: 62.2	Age: 35.4	Age: 52
WOMEN	n = 257	n = 114	n = 130	n = 51
	Age: 63	Age: 62	Age: 37.8	Age: 49.3
OVERALL	n = 471	n = 240	n = 224	n = 92
	Age: 64	Age: 62	Age: 36.8	Age: 50

Conclusion: Our experience shows that CE is a safe and useful tool for the diagnosis of small bowel pathology. We have observed an increasing number of studies along the years, with a high diagnostic yield specially in cases of obscure bleeding.

Disclosure of Interest: None declared

P0858 “SUSPECTED BLOOD INDICATOR” AND “QUICK VIEW” IN SMALL BOWEL CAPSULE ENDOSCOPY FOR OBSCURE GASTROINTESTINAL BLEEDING: A COMPARATIVE STUDY

M. Barbosa¹, P. Carvalho¹, T. Goncalves¹, B. Rosa¹, M. J. Moreira¹, J. Cotter¹

¹Gastroenterology, Centro Hospitalar do Alto Ave, Guimaraes, Portugal

Contact E-mail Address: maraisabelbarbosa@net.sapo.pt

Introduction: Small bowel capsule endoscopy (SBCE) is indicated to evaluate for obscure gastrointestinal bleeding (OGIB). As Standard view (SV) reading is time-consuming, Suspected Blood Indicator (SBI) and Quick View (QV) readings can be useful in the initial evaluation of the VCE study, as they allow for a more rapid reading.

Aims & Methods: To compare the diagnostic accuracy of SBI reading and QV reading versus SV reading in OGIB.

Unicentric retrospective study which included patients who underwent SBCE studies for evaluation of OGIB in a 7-year period. Exclusion criteria: incomplete SBCE and technical recording errors. SBI and QV readings were performed by two independent investigators. The presence of small bowel active bleeding, P2 lesions and QV reading time were recorded. Goldstandard: SV reading.

Results: Three-hundred patients were included: 63.3% female, mean age 62 years, 16.7% with overt OGIB. In SV, active small bowel bleeding was visualized in 31 cases (10.3%) and the bleeding origin was identified in 13 (41.9%). For SBI, the sensitivity was 93.5%, with a negative predictive value (NPV) of 99.3%; for QV, the sensitivity was 100%, with a NPV of 100%. SBI revealed the bleeding origin in 34.5% of the cases and QV in 38.7% of them. In SV, small bowel P2 lesions were visualized in 29.3% of the SBCE. The sensitivity for P2 lesions was 42.0% for SBI and 79.5% for QV, with a NPV of 80.6% and 92.2%, respectively. The mean diagnostic reading time in QV was 2min22s.

Conclusion: Although both modalities are extremely sensitive at identifying active bleeding, Quick View reading detects a higher number of P2 lesions than the Suspected Blood Indicator. In comparison to SBI reading, QV reading is a more accurate diagnostic tool at evaluating patients with OGIB, and it may prove useful as an initial screening in urgent cases.

Disclosure of Interest: None declared

P0859 ENABLING TANDEM PROCEDURE OF COLONOSCOPY FOLLOWING COLON CAPSULE ENDOSCOPY IN COLORECTAL CANCER SCREENING

M. Khoury¹, L. Bredow², F. Khoury¹, A. Sollacher², S. Froschauer-Haefele³, G. Dahlhoff⁴, A. Munte²

¹Gastroenterological Center, Hof, ²Libertamed, Munich, ³Libertamed, Hof, ⁴AOK Bayern, Munich, Germany

Contact E-mail Address: mkhoury@t-online.de

Introduction: Importance of prevention of colorectal carcinoma (CRC) is rising due to increased incidence; yet, acceptance of screening by colonoscopy remains low in Germany. Major reasons are the invasive and intimate character of the colonoscopy itself and the bowel preparation. To overcome these barriers a pilot project by AOK Bayern health insurance in north-eastern Bavaria offers patients aged 45 to 75 to choose between a colon capsule endoscopy (CCE) and screening colonoscopy. If significant findings are discovered during CCE (polyps ≥ 6mm, or ≥ 3 polyps) a so-called tandem procedure is offered: a therapeutic colonoscopy follow-up on the same day with the same bowel preparation, therefore avoiding a second appointment. Feasibility of such a tandem procedure in a non-clinical trial setting has not yet been proven.

Aims & Methods: To allow a tandem procedure, capsule excretion has to be achieved before 3 pm (about 7 hours after capsule ingestion). Following the protocol all patients receive a series of boosts of sodium phosphate to propel the capsule through small and large bowel. To avoid too fast colonic transit, a reduced first boost of 15 ml instead of 30 ml sodium phosphate was given after capsule entry into the duodenum. If CCE was not excreted after 2.5 hours, a second and eventually a third boost after further 2 hours were administered while not exceeding 55 ml of total concentration of sodium phosphate, as recommended in Spada et al. (2012). Percentages were performed to demonstrate that tandem procedure is feasible in clinical practice. Total capsule transit time not exceeding 7 hours was used as outcome criteria.

Results: In total, 260 patients received a CCE from January 2014 – March 2015. In our setting 78% (n = 203) of the CCE was below 7 hours, which allows a tandem procedure. 53 patients (20%) out of the 260 patients needed one boost to complete CCE. 207 patients (80%) received a second boost and out of them 46 (18%) even a third to achieve capsule excretion. 130 (81%) out of 161 patients who received only two boosts would have qualified for a tandem procedure. If a third boost was necessary 43% of the patients would have been able to receive a tandem procedure.

Conclusion: The analysis shows that a tandem procedure of CCE followed by a therapeutic colonoscopy within one day with only one bowel preparation is feasible in a real-world clinical setting. In most of the cases realizing a passage time under 7 hours while producing high-quality video recordings could be achieved with a first boost of 15 ml. However, the quite high percentage of a necessary third boost in our setting suggests that dosages of the first and second boost should be analysed further to potentially reduce the need of a 3^rd one.

Disclosure of Interest: None declared

P0860 REALIZATION OF COLON CAPSULE ENDOSCOPY AND COLONOSCOPY FOLLOW-UP IN TANDEM ON THE SAME DAY IN A REAL-WORLD SETTING

M. Khoury¹, L. Bredow², A. Sollacher², S. Froschauer-Haefele², G. Dahlhoff³, A. Munte²

¹Gastroenterological Center, Hof, ²Libertamed, ³AOK Bayern, Munich, Germany

Contact E-mail Address: mkhoury@t-online.de

Introduction: To increase prevention of colorectal carcinoma (CRC) a pilot project by AOK Bayern health insurance in north-eastern Bavaria offers patients aged 45 to 75 both traditional colonoscopy and colon capsule endoscopy (CCE) as well as a so-called tandem procedure. It enables colonoscopy follow-up on the same day in case of significant findings during CCE, thereby avoiding a second bowel preparation. Aim of this abstract is a description of processes that allow for this tandem procedure.

Aims & Methods: To realize tandem procedure, several organizational and personal requirements need to be considered (see also Krause & Riemann, 2013). At least 3 days before CCE the medical staff needs to inform the patient comprehensively about advantages and disadvantages of traditional colonoscopy, CCE and tandem procedure. Like colonoscopy, CCE preparation involves bowel cleansing including high intake of fluids two days before, a liquid diet one day before and 1.5 l of peg 3350-electrolytes-vitamin C (PEG C) and 2 l water between 6-8 pm the night before CCE. The next morning the patient again has to drink 1 l of PEG C and 2 l of water until 6:30 am, since no fluids should be taken 90 min before swallowing the capsule to ensure quick stomach passage. During CCE the patient should not eat. Optimally, the CCE should start at 8 am in the doctor’s practice to realize capsule excretion before 3 pm. During CCE patients may rest in a recreational room, which allows the medical staff to supervise capsule progress every 30 minutes and to give recommended boosts according to protocol to accelerate passage time. Further, average video analysis time (90 min) needs to be reduced, which can be warranted due to intelligent image recognition software and highly trained staff. If significant findings (polyps ≥ 6mm in size, or ≥ 3 polyps) are observed, the patient may receive a follow-up colonoscopy the same evening without further intake of bowel cleansing. This however requires availability of spatial resources and medical staff until 7 pm.

Results: Following this procedure a colonoscopy on the same day after significant findings during CCE could have been realized in 78% of all screenings. In total, 348 patients opted for a CCE from September 2013 – March 2015.

Conclusion: The pilot project shows that a follow-up colonoscopy the same day than a CCE in case of significant findings can be realized in a real-world practice setting, which avoids a second bowl preparation in case of diagnostic findings. This method however, requires a well-timed and personnel good organized practice as well as a trained doctor. Advantages of a tandem procedure are a non-invasive procedure, only one bowl cleansing, and an intensive medical support. Disadvantages are long fasting times before and during the examination day, preparation early in the morning and spending a whole day in the medical practice.

Disclosure of Interest: None declared

P0861 PANENTERIC CAPSULE ENDOSCOPY: WHOLE GUT VISUALISATION WITHOUT INTUBATION

M. F. Hale¹, K. Drew¹, E. Ejenavi¹, R. Sidhu¹, M. E. McAlindon¹

¹Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield, United Kingdom

Contact E-mail Address: melissa.hale@sth.nhs.uk

Introduction: Capsule endoscopy (CE) is a well-tolerated, first-line small bowel (SB) investigative modality. A specifically adapted version is available to image the colon, thus providing an option for non-invasive, single visit imaging of the entire gastrointestinal tract. This study evaluates a novel panenteric protocol utilised to investigate patients with symptoms which could originate from the SB, large bowel or both sites.

Aims & Methods: Retrospective, single centre, involving consecutive patients attending for panenteric CE between July 2008 and December 2014. PillCam SB (Given Imaging, Israel) or MiroCam (Intromedic, Korea) and PillCam Colon 2 (Given Imaging) were used. All patients with known inflammatory bowel disease (IBD) successfully passed a PillCam Patency device prior. Patient demographics, procedural data, final diagnosis and outcomes were collected.

Results: 108 procedures were performed, mean age 41.5 years (range 16-95), 72 female, median follow up 27 months (range 2-79).

41 patients had known IBD (37 Crohn’s, 4 ulcerative colitis (UC)) and were undergoing disease re-assessment after 12 months of anti-TNF therapy (12), or due to relapse in symptoms (29). The remaining 67 patients had suspected IBD with predominant symptoms of diarrhoea (33), abdominal pain (15), iron deficiency anaemia (8), weight loss (6) and gastrointestinal bleeding (5). 51 patients refused colonoscopy, 37 chose CE over colonoscopy, 17 had an incomplete colonoscopy and 3 were unfit for colonoscopy.

Panenteric capsule endoscopy completion rate (CECR) was 60.1% (65/108), SB CECR 86.1% (93/108) and colon CECR 71.3% (77/108). Colon CE bowel preparation was graded as good or excellent in 61.8%. 2 patients were excluded due to prolonged gastric retention of the colon capsule, 1 subsequently diagnosed with narcotic bowel syndrome. No complications were encountered.

In the IBD group, 25 patients (61.0%) had evidence of active disease, leading to medication alterations in 21, surgery in 1 and conservative management in 3. Of the 16 patients in whom mucosal healing had been achieved, medication regimens were downgraded in 10 patients.

In the suspected IBD group, this was identified in 13.4% (7 Crohn's, 2 UC). Clinically relevant alternative findings included colon polyps (16), diverticular disease (9 colonic, 1 SB), angioectasia (6 SB, 1 colonic) and a small bowel carcinoid (1).

The remaining 24 patients were diagnosed with functional bowel disorders and discharged.

Of all the 34 patients with IBD identified, 22 had ileitis alone, 5 had ileocolonic disease and 7 had colonic disease alone.

Conclusion: Panenteric capsule endoscopy is feasible and can be performed safely in patients known to have IBD. It can be used to guide management without resorting to conventional endoscopy and identifies pathology in all areas of the gastrointestinal tract.

Disclosure of Interest: None declared

P0862 COLON CAPSULE ENDOSCOPY: A USEFUL DIAGNOSTIC MODALITY THAT INFORMS PATIENT MANAGEMENT

M. F. Hale¹, K. Drew¹, E. Ejenavi¹, R. Sidhu¹, M. E. McAlindon¹

¹Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield, United Kingdom

Introduction: Colon capsule endoscopy (CCE) has been demonstrated to be a feasible alternative to colonoscopy for the detection of polyps and neoplasia¹ and avoids intubation and sedation. This study evaluates the utility of CCE in routine clinical practice and its impact on patient outcomes.

Aims & Methods: Retrospective, single-centre, including symptomatic patients attending for CCE using PillCam Colon 2 (Given Imaging, Yoqneam, Israel). All patients with known inflammatory bowel disease (IBD) successfully passed a PillCam Patency device prior. Patient demographics, procedural data, final diagnosis and management outcomes were collected.

Results: 101 patients were included, mean age 43 years (range 16-95), 73 female, median follow-up 29 months (range 1-52). 48% refused colonoscopy, 29% had an incomplete colonoscopy, 17% chose CCE over colonoscopy and 6% were unfit for colonoscopy. Indication for the procedure: anaemia (24%), IBD assessment (16%) and suspected IBD (60%). The latter had predominant symptoms of diarrhoea (77%), abdominal pain (18%) or weight loss (5%). Procedure completion rate 69%, bowel preparation was adequate in 75%. There were no complications.

Results are summarised in Table 1.

In the anaemia group, CCE altered management in 15%: 3 further procedures (1 double balloon enteroscopy (DBE) and argon plasma coagulation, 1 catheter embolisation and 1 small bowel capsule endoscopy) and 1 altered medication. The remaining 20 were managed conservatively.

In the known IBD group, CCE altered further management in 69% (7 altered medication, 2 surgery, 2 further procedures (1 DBE, 1 colonoscopy), the remaining 5 patients were managed conservatively.

In those suspected as having IBD, this was identified in 7%. Other clinically significant diagnoses were made in 36%. The remaining 57% patients were thought to have functional bowel disorders and were discharged. 3 patients were excluded due to a non-diagnostic examination.

Abstract number: P0863

Performance characteristics in the evaluation of the study images
Randomized VC setting	Evaluator	Accuracy for the first reading	Accuracy for the second reading	Difference in accuracy (%) [95% CI]
WLI	1 2 3	61.7 49.1 49.1	54.3 44.6 52.6	-7.4 [-12.5, -2.3]* -4.6 [-8.8, -0.3]* 3.4 [0.0, 6.8]*
	Globally§	53.3	50.5	- 2.9 [- 9.2, 3.5]
FICE 1	4 5 6	63.4 61.4 44.7	52.3 63.4 75.4	-11.1 [-16.2, -6.0]* 2.0 [-3.3, 7.3] 30.7 [24.3, 36.7]*
	Globally§	56.5	63.7	7.1 [-17.0, 31.3]
FICE 2	7 8 9	63.1 65.4 75.7	73.4 58.9 79.4	10.3 [5.3, 15.2]* -6.6 [-12.0, -1.1] *3.7 [-0.5, 7.9]
	Globally§	68.1	70.6	2.5 [-7.1, 12.1]
FICE 3	10 11 12	62.0 58.9 52.6	77.7 50.6 59.7	15.7 [10.1, 21.2]* -8.3 [-14.2, -2.2]* 7.1 [1.3, 12.9]*
	Globally§	57.8	62.7	4.9 [-8.9, 18.6]
Blue Mode	13 14 15	36.9 71.7 68.0	62.3 77.1 76.3	25.4 [19.1, 31.4]* 5.4 [1.0, 9.8]* 8.3 [3.3, 13.3]*
	Globally§	53.7	70.2	16.5 [13.6, 19.4]*

VC, virtual chromoendoscopy; *statistically significant; ^§ stratified McNemar test; WLI, white light image; CI, confidence interval

Conclusion: CCE may be a useful alternative for detecting clinically relevant pathology in symptomatic patients and can help guide management. An incomplete examination (i.e. distal colon not visualised) was less relevant in the 29 patients who had already had an incomplete colonoscopy beforehand or the 24 patients whose incomplete CCE was sufficient to provide a diagnosis. Although marketed as a colonic imaging device, a third of pathology identified by CCE was in the SB, serving as a reminder that it may be difficult to distinguish symptoms arising from the small or large bowel, or both.

Disclosure of Interest: None declared

P0863 USEFULNESS OF VIRTUAL CHROMOENDOSCOPY IN THE EVALUATION OF SUBTLE SMALL BOWEL ULCERATIVE LESIONS BY TRAINEES OR YOUNG GASTROENTEROLOGISTS WITH NO EXPERIENCE IN VIDEOCAPSULE ENDOSCOPY

M. Rimbas¹, D. C. M. Zahiu¹, A. Voiosu¹, T. Voiosu¹, A. Zlate², R. Dinu², D. Galasso³, L. Minelli Grazioli³, M. Campanale³, F. Barbaro³, B. R. Mateescu¹, B. Busuioc², T. Iordache², O. Dolofan², A. M. Popescu⁴, V. D. Balaban⁵, M. Raducan¹, C. Spada³, C. R. Baicus⁶, G. Costamagna³

¹Gastroenterology Department, Colentina Clinical Hospital, Carol Davila University of Medicine and Pharmacy, ²Gastroenterology Department, Colentina Clinical Hospital, Bucharest, Romania, ³Digestive Endoscopy Unit, Catholic University, Rome, Italy, ⁴Gastroenterology Department, Emergency University Hospital, ⁵Gastroenterology Department, Military Emergency Hospital, ⁶Internal Medicine Department, Colentina Clinical Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

Contact E-mail Address: mrimbas@gmail.com

Introduction: Identification of subtle small bowel mucosal lesions by less experienced videocapsule endoscopy (VCE) readers can be challenging, as small differences in mucosal hue or pattern are difficult to detect. To improve lesions’ characterization, chromoendoscopy virtual techniques based on narrowing the bandwidth of the conventional white light endoscopy image (WLI) were developed. However, data on the virtual chromoendoscopy (VC) application in VCE are limited.

Aims & Methods: This multicenter study involved 15 trainees or young endoscopists with good experience in GI endoscopy but no experience in VCE examination. In the first step, they evaluated a WLI selection of mixed de-identified images of 250 unequivocally confirmed difficult to interpret small bowel ulcerative lesions, and 100 artifacts mimicking ulcerative lesions. In the second step, they were randomized in clusters of 3 to evaluate the same images with the addition of one of the VC setting (FICE 1,2,3 and Blue Mode) or in WLI again, labeling them as real or faked. The comparison of accuracies in correctly categorizing the images was performed between the two readings (McNemar’s test).

Results: The results were very heterogeneous. There was a small decrease in accuracy for the second evaluation of WLI pictures. By adding any of the chromoendoscopy settings resulted in an improvement in lesions' characterization; statistical significance was obtained only for Blue Mode (see table).

Table 1.

INDICATION	DIAGNOSIS
NORMAL	POLYPS	FRESH BLOOD	AE	DD	SB ULCERATION	COLITIS	HAEMORRHOIDS
ANAEMIA	10	3	3	2	2	3	1	0
KNOWN IBD	7	0	0	0	0	8	1	0
SUSPECTED IBD	33	16	0	0	4	3	1	1

Conclusion: Virtual chromoendoscopy (especially Blue Mode) seems to help beginner VCE readers in correctly categorizing small bowel mucosal ulcerative lesions.

Acknowledgement: The work has been funded by the Sectoral Operational Programme Human Resources Development 2007-2013 of the Ministry of European Funds through the Financial Agreement POSDRU/159/1.5/S/132395.

Disclosure of Interest: M. Rimbas: None declared, D. Zahiu: None declared, A. Voiosu: None declared, T. Voiosu: None declared, A. Zlate: None declared, R. Dinu: None declared, D. Galasso: None declared, L. Minelli Grazioli: None declared, M. Campanale: None declared, F. Barbaro: None declared, B. Mateescu: None declared, B. Busuioc: None declared, T. Iordache: None declared, O. Dolofan: None declared, A. Popescu: None declared, V. Balaban: None declared, M. Raducan: None declared, C. Spada Consultancy: Given Imaging/ Coviden, C. Baicus: None declared, G. Costamagna Consultancy: Given Imaging/ Coviden

P0864 A NOVEL PREP-LESS X-RAY IMAGING CAPSULE FOR COLON CANCER SCREENING: SAFETY AND PRELIMINARY HUMAN TESTS

N. Gluck¹, N. Arber¹², M. Moshkowitz¹²

¹Department of Gastroenterology, ²Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

Contact E-mail Address: nadira@tlvmc.gov.il

Introduction: The demand for bowel cleansing hampers participation in screening colonoscopy, while poor preparation impairs adenoma detection. A screening method, which generates structure data of the colon, without any cleansing or diet restrictions, would offer an attractive modality for many of the non-compliant patients from the target population.

Aims & Methods

Aims: To evaluate feasibility, safety and outcomes of a novel prep-less X-ray imaging capsule for colon screening.

Device: The capsule is similar in dimensions to other approved capsules. Novel ultra-low dose X-ray based imaging technology (X-Ray radar) generate high-resolution 3-dimensional (3D) imagery of the colon without bowel cleansing. The radar is activated and scans the inner surface only when the capsule is propelled within the colon.

Methods: Capsules were swallowed by ∼20 volunteers (aged 37-66) and tracked during the entire passage of the capsule through the alimentary tract using radio frequency telemetry and a Capsule localization system (CPS). The system performed scans upon detecting effective capsule motion in the colon and transmitted imaging data to an external recorder unit attached to the patients' lower back. Combined data from colon scans and the CPS system were used to reconstruct 3D colon segments in non-prepped colons. Total transit time and total X-ray exposure were calculated to assess the safety profile of the capsule in human subjects.

Results: All capsules were swallowed and eliminated naturally and uneventfully after an average transit time of 68 ± 31 hours. The volunteers were exposed to an ultra-low total radiation dose (average total exposure 0.03 ± 0.007 mSv). The generated traces from various participants present large variability of colon macro structure. Reconstruction of synthetic colon phantoms with and without polyps as well as data from a Bovine colon phantom with induced tissue-made polyps showed spatial resolution of 2–3 mm in colon diameter measurements.

Conclusion: A safety and preliminary efficacy study has been performed using a novel prep-less x-ray imaging capsule for colon cancer screening.

Quantitative ultra-low dose x-ray 3D imaging was achieved in the colon of human subjects. The efficacy of the tracking system and the colon 3D reconstruction will be validated in a multicenter study.

Disclosure of Interest: None declared

P0865 USEFULNESS OF NEW ALGORITHM-IMPLEMENTED READING SOFTWARE FOR SMALL-BOWEL CAPSULE ENDOSCOPY (CE)

N. Ohmiya¹, K. Watanabe², T. Miyazaki³, M. Shimatani⁴, T. Wakamatsu⁴, K. Okazaki⁴, M. Esaki⁵, T. Matsumoto⁶, T. Abe⁷, N. Hosoe⁸, T. Kanai⁸, K. Ohtsuka⁹, M. Watanabe⁹, K. Ikeda¹⁰, H. Tajiri¹¹, M. Nakamura¹², H. Goto¹², T. Tsujikawa¹³, H. Ogata⁸

¹Department of Gastroenterology, Fujita Health University, Toyoake, ²Department of Gastroenterology, ³Osaka City University, ⁴Kansai Medical University Hirakata Hospital, Osaka, ⁵Kyushu University Hospital, Fukuoka, ⁶Iwate Medical University, Morioka, ⁷Keio University Center For Clinical Research, ⁸Keio University Hospital, ⁹Tokyo Medical and Dental University, ¹⁰Jikei University Daisan Hospital, ¹¹Jikei University School of Medicine, Tokyo, ¹²Nagoya University Graduate School of Medicine, Nagoya, ¹³National Hospital Organization Higashi-Ohmi General Medical Center, Higashi-Ohmi, Japan

Contact E-mail Address: nohmiya@fujita-hu.ac.jp

Introduction: Reading of tens of thousands of CE images is labor-intensive and time-consuming. Olympus Corp. has developed a new algorithm to minimize redundant images so that all the areas captured by CE can be displayed.

Aims & Methods: The co-primary endpoints in this study were (1) to demonstrate the non-inferiority of this new algorithm modality showing only selected images in reading major and minor lesions compared to the control (EC-10 normal mode modality) showing all the images in terms of the number of true positives (TP), and (2) to demonstrate the superiority of this modality to the control in reading time. Multicenter crossover study was performed at 8 hospitals in Japan. This study consisted of 7 readers and 3 adjudication committee members, 2 reading modalities, and 40 patients with various small-bowel pathology reviewed and documented by 3 judging members from 60 patients with suspected small-bowel diseases (10 patients from 6 hospitals). Each patient’s images were read by randomly-allocated 2 readers, each of whom used each modality for each patient (i.e. Doctor A: the new modality followed by the control, Doctor B: the control followed by the new modality). The reading modalities were switched after a certain interval more than 2 weeks. Thereby, this amounted to a total of 4 readings per patient. The adjudication committee defined clinically relevant lesions as major lesions, and irrelevant subtle lesions as minor lesions. A priori non-inferiority margin of 0.9 was established.

Results: Estimated ratios of detection rates of total, major, and minor lesions with the new modality compared to the control were 0.87 (0.80-0.95), 0.93 (0.83-1.04), and 0.83 (0.74-0.94), respectively. Although non-inferiority was not demonstrated with the new modality, the detection rate of major lesions was not significantly different between the new modality and the control. The reading time of the new modality and the control was 27.3 and 75.1 minutes, respectively, the difference of which was -47.7 minutes (-52.0,-43.4)(P<0.001).

Conclusion: The Olympus new algorithm-implemented reading software significantly shortened the reading time without declining detection rate of major lesions, although non-inferiority was not demonstrated in detecting all small-bowel lesions.

Disclosure of Interest: None declared

P0866 POLYETHYLENE GLYCOL SOLUTION PRIOR TO SMALL BOWEL CAPSULE ENDOSCOPY – DOES IT HELP?

O. S. Omer¹, S. Salehi¹, D. De Coster¹, M. Wong¹, L. Pee¹, A. McNair¹

¹Gastroenterology, Queen Elizabeth Hospital, Woolwich, London, United Kingdom

Contact E-mail Address: a.mcnair@nhs.net

Introduction: The diagnostic yield of capsule endoscopy (CE) relies heavily upon obtaining clear luminal views and is often hampered by biliary secretions, small intestinal fluid and bubbles. Studies assessing the efficacy of bowel preparation in CE have been inconsistent and a general consensus on this matter has not been reached. Our department has recently moved from a pre-procedure regimen of 24 hours of clear fluids only, to 24 hours of clear fluids and the addition of a single sachet of polyethylene glycol (PEG) solution the evening prior to CE. To investigate the effect of this change, we performed a retrospective review of CE findings in patients who received PEG solution vs. clear fluids.

Aims & Methods: Patients who underwent CE from August 2013 to March 2015 were indentified using Rapid® capsule endoscopy software. This provided an even distribution of patients receiving PEG solution vs. clear fluids only. Data were collected on patient demographics, indication for CE and clinical findings. Three independent assessors then reviewed image quality of capsule footage at 20 minute intervals to examine the bowel preparation. Overall adequacy was determined as ‘adequate’ or ‘inadequate’ (views of mucosa obscured by cloudy fluid or bubbles in a high proportion of images) by consensus opinion. Lesion detection rates were then calculated for patient groups. Comparisons between groups were performed using chi-square analysis.

Results: A total of 62 patients were identified: 31 (50%) received polyethylene glycol (PEG) solution and 31 (50%) received clear fluids only (CF) prior to CE. There were no significant differences in patient demographics between PEG and CF groups (mean age 50 vs. 52, and M:F 20:11 vs. 18:13, respectively). Indications for CE included obscure gastrointestinal (GI) bleeding (18 in PEG group vs. 22 in CF) and possible small bowel Crohn’s disease (13 in PEG group vs. 9 in CF). There were no significant differences in lesion detection rate between the two groups when all lesions, including those deemed clinically insignificant (e.g. minor aphthous ulceration) were analysed (90.3% PEG group vs. 83.9% CF, p=0.45). When these lesions were excluded, the detection rate for clinically significant lesions in the PEG group was significantly higher than that in the CF group (58.1% vs. 32.3%, p < 0.05). Moreover, a significantly higher proportion of patients had ‘adequate’ image quality following bowel preparation in the PEG group vs. CF group following independent assessment (74.2% vs. 48.4%, p < 0.05).

Conclusion: We conclude that moving to a regimen of clear fluids and a single sachet of PEG solution prior to CE has significantly improved our detection rate of clinically significant lesions. This may be explained by improved image quality and adequacy of bowel preparation associated with PEG solution. Larger prospective studies comparing different bowel cleansing regimens (including a ‘full’ bowel preparation as taken prior to colonoscopy) are needed to firmly establish the ideal preparation for capsule endoscopy.

Disclosure of Interest: None declared

P0867 STANDARTIZATION OF VIRTUAL NAVIGATOR WORK IN ABDOMINAL RADIOLOGY

I. Timashkov¹, A. Borsukov¹

¹Problem Scientific Research Laboratory, SSMU, Smolensk, Russian Federation

Contact E-mail Address: Ivan.Timashkov@gmail.com

Introduction: The essence of the virtual navigator is to synchronize the real-time data obtained by ultrasound and MSCT / MRT. There are 2 modes of synchronization: 1-manual alignment of the plane and point 2-technology automatically align with a magnetic sensor - Active Tracker. The scientific sources available to us is not given a standardized method of using the device Active Tracker, depending on the zone of interest.

Aims & Methods: In order to standardize the work of the virtual navigator LOGIQ E9 in abdominal radiology surveyed 11 people (6 male, 5 female) with different pathologies of the abdominal cavity during 2014. Algorithm examination consisted of 3 phases. The first phase was carried out ultrasound research of the abdomen, which determines the location of the pathological focus in the abdomen. The second stage was carried out MSCT of the abdomen (model Toshiba Aquilion) superimposed on the anterior abdominal wall unit Active Tracker. In the third phase image obtained by MSCT were loaded on the console LOGIQ E9, where the automatic synchronization of the image obtained by MSCT and ultrasound research in real time using the device Active Tracker. We have proposed a method of standardization Active Tracker device location on the anterior abdominal wall at pathological foci ranging in 1- the right lobe of the liver, 2 - the left lobe of the liver, 3- pancreas, 4- right kidney, 5-, left kidney. In the study of the pathological focus in the right lobe of the liver is necessary to have Active Tracker midline at a distance of 7-8 cm from the edge of the xiphoid process. In the study of the pathological focus in the left lobe of the liver is necessary to have Active Tracker midline at a distance of 10-11 cm from the edge of the xiphoid process. In the study of the pathological focus in the pancreas is necessary to have Active Tracker midline at a distance of 12-13 cm from the edge of the xiphoid process. In the study of the pathological focus in the right kidney is necessary to have Active Tracker on the right midclavicular line in the 7-8 intercostal space. In the study of the pathological focus in the left kidney is necessary to have Active Tracker on the left midclavicular line in the 7-8 intercostal space.

Results: The standardization work of the virtual navigator has led to a reduction in the time synchronization of images from 15-20 minutes to 3-7 minutes, increase the accuracy of coincidence of the two images (with 78% for the standard method to 92% with improved), reducing the number of operator errors when synchronizing images.

Conclusion: Thus, we developed a technique proved its efficiency and propose to use when working with virtual navigation.

Disclosure of Interest: None declared

P0868 ENDOSCOPIC ULTRASONOGRAPHY-GUIDED INTERSTITIAL BRACHYTHERAPY BASED ON SPECIAL TREATMENT-PLANNING SYSTEM FOR UNRESECTABLE PANCREATIC CANCER: A PILOT STUDY

Y. Liu¹, M. Min¹, Y. J. Wu²

¹Affiliated Hospital of Academy of Military Medical Sciences, Beijing, ²Information Science and Engineering School, Fudan University, Shanghai, China

Contact E-mail Address: minmin823@sina.com

Introduction: EUS-guided interstitial brachytherapy is promising in the treatment of unresectable malignant carcinoma adjacent to the digestive tract. The feasible treatment plan is not established.

Aims & Methods: To develop a novel treatment plan and evaluate the feasibility in patients with unresectable pancreatic cancer.14 patients with unresectable pancreatic cancer.A special treatment-planning system (TPS) for EUS was designed and evaluated by comparing with the traditional TPS. (IIIstage: 6; IVstage: 8) underwent EUS-guided interstitial brachytherapy based on the new software.

Results: In the test model, there was no obvious difference of irradiation doses calculated by the two softwares (EUS TPS vs. traditional TPS) (P > 0.05). Under the support of EUS TPS, a novel treatment plan for EUS-guided interstitial brachytherapy was successfully established, which contained seven principles. All patients tolerated the treatment well without any serious complications. In 5 patients (stage III) that the minimal peripheral dose was larger than 90Gy, the PD rate was 80%(4/5).Four patients (4/6) in stage III were alive for more than 12 months with a median peripheral dose of 107.5 Gy. The expected median survival time of the 14 patients was 9.0 months (95%CI, 7.6–10.4 months).

Conclusion: The results demonstrated that the new EUS TPS will play an important role in EUS-guided interstitial brachytherapy in patients with unresectable malignant carcinoma.

Disclosure of Interest: None declared

P0869 TYPE OF COMBINED ENDOSCOPIC BILIARY AND GASTRODUODENAL STENTING IS A SIGNIFICANT FACTOR FOR BILIARY ROUTE MAINTENANCE

T. Sato¹², K. Hara², N. Mizuno², S. Hijioka², H. Imaoka², A. Nakajima¹, K. Kubota¹, K. Yamao²

¹Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, ²Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan

Contact E-mail Address: tkmtsato@yokohama-cu.ac.jp

Introduction: Some patients with malignant gastric outlet obstruction require combined biliary and gastroduodenal stenting (double stenting)¹, but there is often difficulty performing biliary re-intervention for stent dysfunction, and the optimal biliary stenting for such cases remains controversial².

Aims & Methods: From the perspective of biliary re-intervention, 43 consecutive patients who successfully underwent endoscopic double stenting with metallic stents were reviewed, and features of double stenting and clinical outcomes were evaluated. The present study aimed to clarify what affects for long-term maintenance of the biliary drainage route.

Results: All patients with biliary stent dysfunction were studied, and univariate analysis showed that the separate type of double stenting (two stents placed not in a crossed position) was a unique predictive factor related to successful biliary re-intervention for stent dysfunction (odds ratio 73.67, P=0.001). From the comparison of clinical features between the separate and cross (two stents placed in crossed position) types, cases with biliary stenting before gastroduodenal stenting (P=0.008) and transpapillary biliary drainage (P=0.01) tended to become the cross type. There were no significant differences in overall survival and the biliary stent dysfunction rate, but the Kaplan-Meier method showed that the separate type was superior for biliary stent patency after double stenting (P=0.04). Moreover, the initial biliary route maintenance rate was significantly higher in the separate type, with an estimated hazard ratio of 0.25 (95% confidence interval, 0.061-0.99; P < 0.001).

Conclusion: The separate type of double stenting might contribute to successful biliary re-intervention and maintain the drainage route longer. Technical considerations of biliary drainage should be considered in order to perform the separate type of double stenting.

Disclosure of Interest: None declared

TUESDAY, OCTOBER 27, 2015   09:00-17:00

SURGERY II – HALL 7__________

P0870 INDICATION FOR THE PLACEMENT AND THE REMOVAL OF PROPHYLACTIC DRAINS FOLLOWING HEPATECTOMY

A. Oshita¹², M. Sasaki¹, A. Nakamitsu¹

¹Gastroenterological Surgery, JA Hiroshima General Hospital, Hatsuka-ichi, ²Gastroenterological Surgery, Hiroshima Prefectural Hospital, Hiroshima, Japan

Contact E-mail Address: oshita-akihiko@umin.ac.jp

Introduction: Although abdominal prophylactic drains following hepatectomy is still controversial, they have been routinely placed in most of institutions for hepato-biliary-pancreatic surgery. The present study was aimed to establish the indication to place prophylactic drains after hepatectomy and the optimal time for their removal.

Aims & Methods: From June 2011 to December 2014, consecutive 77 cases underwent hepatectomy without biliary reconstruction for benign and malignant liver tumors in JA Hiroshima General Hospital. Of them, prophylactic drains were placed in 60 cases whose Glissonean pedicles of more than 2 mm in diameter were ligated or clipped and divided. Perioperative data were prospectively collected and analysed. Bilirubin levels in drain fluid were measured on postoperative day (POD) 3 after surgery. Drains were removed on POD 3 or 4 if the drain-fluid bilirubin level was less than three times as the serum level of bilirubin according to the International Study Group of Liver Surgery (ISGLS). As postoperative complications related with placement of prophylactic drains, biliary leakage was analysed and classified into two groups: one is early biliary leakage (EBL) when diagnosed within POD 10. The other is delayed biliary leakage (DBL) when diagnosed after POD 11.

Results: Biliary leakages of Grade A and B according to ISGLS were observed in 6 cases (7.8%). The drain-fluid bilirubin level more than three times as the serum level of bilirubin was observed only in one case, treated conservatively by repeated replacement of drainage (Grade A). In the rest of 59 cases, placed with prophylactic drains, they were removed on mean POD 3.5. Of them, five cases were treated with re-drainage on mean POD 19.0 (ranging from 11 to 30) and four cases were co-treated with endoscopic nasal biliary drainage (Grade B). On multivariate analysis, the exposure of Glissonean pedicles of more than 2 cm in the major axis was the strongest predictor of biliary leakage (odds ratio 14.210, 95 per cent confidence interval 1.289 to 156.717; p = 0.03).

Conclusion: Prophylactic drains might be essential in hepatectomy, exposing the Glissonean pedicle. The optimal time for their removal according to the ISGLS criteria of biliary leakage was thought to be appropriate for EBL. However, the careful observation is also needed after POD 11 for DBL.

Disclosure of Interest: None declared

P0871 POSTTRANSPLANT PEAK C-REACTIVE PROTEIN CORRELATES WITH ISCHEMIA-REPERFUSION INJURY AND RECURRENCE-FREE OUTCOME IN LIVER TRANSPLANT PATIENTS WITH HCC

A. Kornberg¹, U. Witt², J. Kornberg³⁴, H. Friess¹, K. Thrum⁵

¹Surgery, ²TU Munich, ³LMU, Munich, Germany, ⁴Anesthesiology, LMU, Munich, ⁵Pathology, Helios Klinikum, Berlin, Germany

Contact E-mail Address: ArnoKornberg@aol.com

Introduction: Ischemia reperfusion (I/R) injury was shown to promote intra- and extrahepatic tumor outgrowth in liver transplant patients with hepatocellular carcinoma (HCC). C-reactive protein (CRP) is a parameter of inflammatory response to surgical trauma.

Aims & Methods: The aim of this study was to determine the correlation of posttransplant peak CRP-level with I/R-induced hepatocellular damage and recurrence-free outcome following liver transplantation (LT) for HCC. 103 liver transplant patients with HCC were included. Patients were classified as Milan In and Milan Out, based on explant histopathology data. By ROC-analysis, the most optimal cut-off post-LT peak CRP-level for overall and recurrence-free outcome was determined. Peak CRP values along with other established clinicopathologic variables were correlated with early hepatocellular damage (transaminases, hepatic artery resistive index) and tumor-specific outcome.

Results: ROC-analysis defined an optimal cut-off peak CRP-level of 3.5 mg/dl for overall and recurrence-free survival. In the high CRP-group (< 3.5 mg/dl), hepatocellular damage was higher and hepatic artery perfusion more compromised than in the low CRP-group (≤ 3.5 mg/dl; P < 0.001). Five patients in the low CRP-group (7.8%), but 19 patients of the high CRP-subset (48.7%) developed HCC relapse post-LT (P < 0.001). The 1- and 5-year disease-free survival rates were 95.3% and 91.7% in the low CRP-group, but 89.5% and 48.7% in high CRP-subset (P < 0.001). In multivariate analysis, presence of microvascular invasion (Hazard ratio [HR] 10.9), peak CRP > 3.5 mg/dl (HR 4), AFP-level > 400 IU/ml (HR 3) and total ischemia time > 450 min (HR 3.4) were identified as independent predictors of HCC relapse. In Milan In patients, CRP level had no predictive value. In contrast, peak CRP-value (HR 5.8) together with microvascular invasion (HR 8.3) were identified as the only independent predictors of recurrence-free survival in Milan Out recipients. The 1- and 5-year recurrence-free survival rates in this special subset were 94.4% and 88% the low (n = 36), but only 87.8% and 29.3% in the high CRP-patients (n = 25; P < 0.001).

Conclusion: Early posttransplant peak CRP correlates with I/R-induced hepatocellular injury and risk of HCC recurrence. In particular patients with HCC exceeding the Milan criteria might benefit from targeting inflammatory mechanisms.

Disclosure of Interest: None declared

P0872 POST CHOLECYSTECTOMY BILIARY INJURIES: ONE CENTER EXPERIENCE

G. Elebidy¹, O. Fathy¹, E. Atif¹, A. Abdelraof¹, A. Sultan¹

¹General Surgery, Gastroenterology Surgical Center, Mansoura, Egypt

Contact E-mail Address: dr.ehab.atif@gmail.com

Introduction: Laparoscopic cholecystectomy has lead to a rise in the incidence of BDIs from 0.1-0.2% in OC to 0.4-0.6% after LC.¹ The early and accurate diagnosis of postcholecystectomy BDIs is mandatory for surgeons and gastroenterologists, because unrecognized or badly managed BDIs lead to serious complications such as biliary cirrhosis, hepatic failure and even death.² The choice of the appropriate treatment for BDIs is very important, because it may avoid these serious complications and improve quality of life among these patients. Therefore, the question regarding the type of treatment for patients with BDIs is still a matter of debate. Initially, endoscopic treatment is recommended in patients with BDIs. When endoscopic techniques are not effective, surgical reconstruction is performed.³ The management of BDIs is a surgical challenge that needs collaboration among surgeons, gastroenterologists and interventional radiologists at tertiary referral centers.^4,5

Aims & Methods: Between 1995 and 2012, 330 patients with post-cholecystectomy bile duct injuries presented to Gastroenterology Surgical Center, Mansoura University, Egypt.

Results: Of the studied patients, 232 were females and 98 patients were males. Their mean age was 38 years ± 12. 63% of the patients were referred from private hospitals while 34.5% were referred from primary hospitals. 252 patients had open cholecystectomies while 78 patients had laparoscopic cholecystectomies. Regarding the type of injuries according to Strasberg-Bismuth classification, the most common was type E2 injury (31.2%) followed by type A injury (20.6%). According to the time of diagnosis, 10 patients were diagnosed intra-operatively, 236 patients were diagnosed early (within one month of the cholecystectomy) and 84 patients were lately diagnosed ( more than one month after the cholecystectomy). Patients presented with generalized peritonitis, localized peritonitis with fistulae or with progressive jaundice.

229 patients were managed surgically where 217 patients underwent bilio-enteric reconstruction while 122 were managed by endoscopic dilatation and stent out of which 21 patients needed surgical reconstruction after failed repeated dilatations.

87.3% of patients who were managed surgically showed excellent outcomes according to Johns Hopkins criteria compared to 78.6 % for endoscopic management.

Conclusion: As a conclusion, early diagnosis of iatrogenic bile duct injuries together with management by experienced hepatobiliary surgeon greatly improves the patient outcomes.

Disclosure of Interest: None declared

P0873 APPLICATION OF HEPATOBILIARY SCINTIGRAPHY FOR THE IDENTIFICATION OF HIGH-RISK PATIENTS REQUIRING PREOPERATIVE PORTAL VEIN EMBOLIZATION

K. P. Cieslak¹, R. J. Bennink², W. de Graaf³, M. G. Besselink¹, O. R. Busch¹, D. J. Gouma¹, T. M. van Gulik¹

¹Surgery, ²Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands, Amsterdam, ³Gastroenterology & Hepatology, Erasmus Medical Center, Rotterdam, Netherlands

Contact E-mail Address: k.p.cieslak@amc.nl

Introduction: Patients with insufficient future remnant liver (FRL) are at risk of developing postoperative liver failure (LF) and are candidates for preoperative portal vein embolization (PVE). ^99mTc-mebrofenin-hepatobiliary-scintigraphy (HBS) is a quantitative method enabling functional assessment of the FRL with a validated cut-off value for safe resection (2.7%/min/m²). Other, mathematical methods of preoperative FRL-assessment, like FRL/body-weight ratio (FRL-BWR) and standardized (estimated) volumetry, claim to accurately assess the FRL.

Aims & Methods: The aim of this study was to evaluate the above mentioned methods in the identification of patients requiring preoperative PVE. From November 2006 to June 2014, preoperative HBS and CT-volumetry followed by major liver resection (≥3 segments) were performed in 169 patients. Patients with FRL volume <25% and/or FRL function <2.7%/min/m2 were considered for preoperative PVE. We compared CT-volumetry in combination with HBS with FRL-BWR (cut-off value 0.5% patient’s weight) and estimated volumetry (cut-off value 25% of estimated total liver volume). The endpoints were the differences in FRL-evaluation between the methods.

Results: 29/169 (17.2%) patients underwent preoperative PVE. The median FRL percentage of the total liver volume before PVE was 23.7% (IQR 18.7-27.8). The median FRL-function was 1.9%/min/m2 (IQR 1.50-2.36). In 8/29 (27.6%) of these patients, PVE was performed because FRL-function was below the cut-off value in spite of FRL-volume ≥25%. Median FRL-BWR was 0.52% (IQR 0.40-0.70) and median estimated FRL was 24.5% (IQR 18.34-29.43). According to BWR-FRL and estimated volumetry, 16/29 (55.2%) and 14/29 (48.3%) patients, respectively, had sufficient FRL and would not have undergone PVE if the decision was based on these methods. 1/29 (3.4%) patient developed LF resulting in death. This patient had insufficient FRL according to all the above mentioned methods.

Conclusion: Non-functional FRL-assessment may lead to overestimation of the FRL. HBS provides useful information for the identification of patients requiring preoperative portal vein embolization.

Disclosure of Interest: None declared

P0874 ASSESSMENT OF LIVER FUNCTION IN PATIENTS UNDERGOING MAJOR LIVER RESECTION USING HEPATOBILIARY SCINTIGRAPHY

K. P. Cieslak¹, R. J. Bennink², W. de Graaf³, M. G. Besselink¹, O. R. Busch¹, D. J. Gouma¹, T. M. van Gulik¹

¹Surgery, ²Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands, Amsterdam, ³Gastroenterology & Hepatology, Erasmus Medical Center, Rotterdam, Netherlands

Contact E-mail Address: k.p.cieslak@amc.nl

Introduction: ^99mTc-mebrofenin-hepatobiliary-scintigraphy (HBS) is a quantitative method enabling functional assessment of the future remnant liver (FRL-function). In a previous validation study, we determined a single cut-off value of 2.7%/min/m² in patients with non-compromised and compromised liver parenchyma, for the prediction of postoperative liver failure (LF).

Aims & Methods: The aim of this study was to evaluate the value of HBS in the preoperative assessment of patients eligible for major liver resection. From November 2006 to June 2014, 169 patients, of which 71/169 (42.0%) with (peri)hilar cholangiocarcinoma, underwent major liver resection (≥3 segments) after preoperative HBS and CT-volumetry. Patients with FRL-volume <25% and/or FRL-function <2.69%/min/m² were considered for preoperative portal vein embolization (PVE). The study endpoints were postoperative LF and LF related mortality.

Results: 29/169 (17.2%) patients underwent preoperative PVE. Median FRL-volume prior to PVE was 23.7% (IQR 18.7-27.8) of total liver volume. Median FRL-function was 1.9%/min/m² (IQR 1.50-2.36). In 8/29 (27.6%) of these patients, PVE was performed because FRL-function was below the cut-off value in spite of FRL-volume ≥25%. Major hepatectomies comprised 72 (42.6%) right and 56 (33.1%) left hemihepatectomies, 30 (17.8%) extended right and 6 (3.6%) extended left hemihepatectomies, 2 (1.2%) central resections and 3 (1.8%) segmentectomies of ≥3 liver segments. Overall, clinically relevant complications (≥ Clavien-Dindo grade 3a) were seen in 66/169 (39.1%) patients. LF (overall 2.4%) was seen in 3/140 (2.1%) of the non-PVE patients and in 1/29 (3.4%) of the PVE patients while LF related mortality (overall 1.8%) occurred in 2/140 (1.4%) of non-PVE vs. 1/29 (3.4%) of the PVE patients. There were no significant differences in postoperative outcomes between PVE and non-PVE patients.

Conclusion: Preoperative HBS provides useful functional information on the FRL in patients requiring major liver surgery. Patients with sufficient FRL-volume but decreased FRL-function may benefit from preoperative portal vein embolization.

Disclosure of Interest: None declared

P0875 ARE “TAKE HOME” BOX TRAINERS AS GOOD AS HIGH FIDELITY, VIRTUAL REALITY (HFVR) SIMULATORS IN ACQUIRING LAPAROSCOPIC SURGICAL SKILLS?

M. Yiasemidou¹, J. de Siqueira¹, D. Glassman², J. Tomlinson¹, M. Gough¹

¹School of Surgery, Health Education Yorkshire and the Humber, Leeds, ²MidYorks Medical Education and Simulation Hub, Wakefield, United Kingdom

Contact E-mail Address: marinayiasemidou@gmail.com

Introduction: High Fidelity Virtual Reality (HFVR) simulators have been proposed as providing optimum training for laparoscopic procedures such as cholecystectomy. However, purchase and maintenance costs have compromised widespread use of this type of equipment. Further, recent short-term studies have demonstrated equal or greater efficacy of supervised training programmes using simple box trainers (BT) compared to HFVR simulators.

Aims & Methods

Aim: This study explores the value of independent learning using a BT over a longer period of training, compared to the same duration of “free access” to HFVR simulators.

Methods: 16 surgical trainees who had performed fewer than 15 laparoscopic cholecystectomies were recruited to this study and randomised into two groups: the BT Group were to be provided their own BT whilst the HFVR Group were subsequently offered free access to a HFVR. Prior to commencing their allocated training programme all trainees performed laparoscopic cholecystectomy on a HFVR simulator from which the simulator-derived matrix scores were collected. Subsequently both groups were asked to practice 3 simple tasks (peg transfer, clip applying and precision cutting) for 6 weeks (20 repetitions of each) using their allotted training tool. Finally trainees performed a second laparoscopic cholecystectomy on the HFVR simulator from which the same matrix scores were determined. Change in performance from baseline to the second assessment was compared between the groups.

Results: The BT group improved significantly in respect of the number of movements (before median, (25^th -75^th percentile) 1419 (893.5-1689), after 466 (324-888.5), p = 0.021) performed and total path length (PL before mean 2951.58 (2037.6-4258.5) after 1610.57 (906.05-2211.85), p = 0.024). The time to perform cholecystectomy was not statistically reduced (before mean, 1373.22 sec (1057-1880) after 749.22 (294.5-1071.5), p = 0.051). In contrast, there was no statistically significant improvement in any of the matrices in the VR group (time before mean 923.71 sec (317-1238) after 820.29 (430-1264), p = 0.920; NOM before median 760 (430-1264) after 964 (608-1442), p = 0.446; PL after mean 1856.3 (981-2739.4) after 2393.9 (939.9-3056.3), p = 0.425). Inter-group comparison of these parameters showed no difference in the reduction in time to perform cholecystectomy (Time BT mean 624sec (-2-1422) HFVR: -33.24 (-968-639) sec p = 0.137). However the BT group performed significantly better in terms of NOM (BT median 447 (112-1416) HFVR -182 (-811-337), p = 0.031) and PL (BT mean 1341.01 (172.6-2800.7) HFVR -537.6 (-2210-1011.2), p = 0.03). These differences could be explained by the number of repetitions performed by each group (BT: median 20 (20-25) v HFVR: 10 (2-10), p = 0.008).

Conclusion: There are strong indications that longer-term practice on a “take-home” BT may be more effective for the acquisition of laparoscopic skills, compared to VR simulators. This may be explained by the greater opportunity for practice with the BT.

Disclosure of Interest: None declared

P0876 CLINICOPATHLOGICSTUDY OF MINIMUM INVASIVE SURGERY AND ENDOSCOPIC PAPILLECTOMY FOR TUMOR OF THE AMPULLA OF VATER

M. Hamano¹

¹Surgery, Gastroenterology, Tokyo, Japan

Contact E-mail Address: hamano.mie@tymc.ac.jp

Introduction: Ablative therapy is required for patients with pathological abnormalities at The Tumor of the Ampulla of Vater: in particular, carcinomas, adenomas and carcinoids. Adenomas are benign lesions, but because suspicions are raised about adenoma-carcinoma sequence during the process of developing adenoma, a treatment for premalignant lesions also needs to be considered. Local excision of the Ampulla of Vater and partial duodenectomy as Minimum Invasive Surgery for adenomas and early carcinomas have been performed at our hospital since 1989. For the case of adenomas, endoscopic Papillectomy has also been carried out. A decision regarding the adequacy of borderline lesions has been made by a discussion with gastroenterologists in our hospital. In the present study, the adequacy of borderline lesions and results of it were examined by attempting to compare between endoscopic Papillectomy and Local excision of Tumor of the Ampulla of Vater.

Aims & Methods: From 1989 ∼ 2014, 18 patients underwent Local excision of the Ampulla of Vater, 2005 ∼ 2013, 12 patients underwent endoscopic Papillectomyrespectively. We examined in terms of clinicopathlogical findings, complications?background, curability and the postoperative hospitalization days.

Results: 18 patients underwent Local excision of the Ampulla of Vater, and another 12 patients were given endoscopic Papillectomy. The patients who underwent Local excision were histopathologically diagnosed as follows: 9 patients with papilla cancer, 8 patients with adenoma, and 1 patient with carcinoid; meanwhile, the patients who underwent endoscopic Papillectomy were as follows: 2 patients with papilla cancer, 8 patients with adenoma, 1 patient with carcinoid, and 1 patient with polyp. The number of patients who received a diagnosis of adenoma before surgery but who were recognized as malignancy after surgery was 4 in Local excision of the Ampulla of Vater and 2 in endoscopic Papillectomy. Resection stumps in 3 patients who were given endoscopic Papillectomy were partially unclear, but there was 1 patient with positive surgical margins. The number of patients who suffered complications before surgery was 3 in Local excision, but none were in endoscopic Papillectomy. The average of a hospital stay after surgery was 18.5 days in Local excision of the Ampulla of Vater and 11.6 days in endoscopic Papillectomy. The number of patients who suffered complications after surgery in Local excision of the Ampulla of Vater was 1 patient with pancreatitis, and that in endoscopic Papillectomy was 5 patients with bleeding, 3 patients with inflammation of the gall bladder and the bile duct, and 2 patients with pancreatitis. 1 patient had a prognosis of stump recurrence (adenoma) in endoscopic Papillectomy, but others were alive without evidence of any cancer.

Conclusion: Patients had neither severe complication nor cancer recurrence in both Local excision of the Ampulla of Vater and Endoscopic papillectomy; therefore, a decision regarding the adequacy of borderline lesions in our hospital was thought to be responsible.

Because patients had a good prognosis in both therapeutic procedures, each benefit was thought to be utilized by greatly considering the adequacy of borderline lesions and choosing surgical procedures, and appropriate medical care for patients was also thought to be provided by means of the lowest operative stress on borderline lesions.

Disclosure of Interest: None declared

P0877 IN SITU HYPOTHERMIC PERFUSION WITH RETROGRADE OUTFLOW DURING RIGHT HEMIHEPATECTOMY: FIRST CLINICAL EXPERIENCES

P. Olthof¹, M. Reiniers¹, R. van Golen¹, M. Heger¹, T. van Gulik¹

¹Surgical Laboratory, Academic Medical Center, Amsterdam, Netherlands

Contact E-mail Address: p.b.olthof@amc.nl

Introduction: A new technique of selective in situ hypothermic perfusion with retrograde outflow (IHP-R) was developed. The outcomes of IHP-R were assessed during right hemihepatectomy in a randomized controlled clinical trail.

Aims & Methods: After right liver mobilization, the right branch of the portal vein (RPV) and the right hepatic artery (RHA) were clamped and cut. Following RHA cannulation, the portal triad was clamped, the right hepatic vein was closed and cut, and the middle/left hepatic veins were clamped to exclude the liver from the circulation. The left hemiliver was perfused through the RHA using cold Ringer’s lactate solution (target liver temperature of 28°C), allowing retrograde outflow via the cut end of the RPV until parenchymal transection was completed.

Fourteen patients were randomized between IHP-R and the standard procedure. Outcomes included laboratory parameters (AST, ALT, total bilirubin), transfusion requirements, complications, ICU stay, functional liver regeneration (assessed preoperatively and at postoperative day (POD) 3 by hepatobiliary scintigraphy with SPECT), and hospital stay.

Results: There were no statistical differences regarding baseline demographic and clinical characteristics. The median/range IHP-R times were 45/43–55 min while the target temperature of 28°C was reached in 6 of 7 IHP-R patients. Ischemia time, resection type, transfusion requirements, ICU stay, complications, and hospital stay were not different between groups. Procedure duration was longer in the IHP-R group (454/371-494 versus 330/256-351 min, p =0.007). Postoperative AST and bilirubin were not different between groups, however peak ALT levels were higher in the IHP-R group (512/399-667 versus 397/214-415 U/L, p=0.038). There was significant functional liver regeneration within the IHP-R but not in the control group on POD-3 compared to preoperatively calculated values (p=0.018), suggesting early and possibly improved functional liver regeneration following IHP-R.

Conclusion: IHP-R allows easy and safe cold liver perfusion. The higher peak in ALT levels following IHP-R might be due to the prolonged procedure duration. Nevertheless, IHP-R induces early, and possibly improved liver regeneration following major liver resection.

Disclosure of Interest: None declared

P0878 PERCUTANEOUS PREOPERATIVE BILIARY DRAINAGE FOR RESECTABLE PERIHILAR CHOLANGIOCARCINOMA: NO ASSOCIATION WITH SURVIVAL AND NO INCREASE IN SEEDING METASTASES

J. K. Wiggers¹, B. Groot Koerkamp², R. J. S. Coelen¹, A. Doussot³, S. van Dieren⁴, E. A. Rauws⁵, M. A. Schattner⁶, K. P. van Lienden⁷, K. T. Brown⁸, M. G. Besselink¹, G. van Tienhoven⁹, P. J. Allen³, O. R. C. Busch¹, M. I. D'Angelica³, R. P. DeMatteo³, D. J. Gouma¹, P. Kingham³, J. Verheij¹⁰, W. R. Jarnagin³, T. M. van Gulik¹

¹Surgery, Academic Medical Center, Amsterdam, ²Surgery, Erasmus Medical Center, Rotterdam, Netherlands, ³Hepatobiliary and Pancreatic Surgery, Memorial Sloan Kettering Cancer Center, New York, United States, ⁴Clinical Research Unit, ⁵Gastroenterology, Academic Medical Center, Amsterdam, Netherlands, ⁶Gastroenterology, Memorial Sloan Kettering Cancer Center, New York, United States, ⁷Interventional Radiology, Academic Medical Center, Amsterdam, Netherlands, ⁸Interventional Radiology, Memorial Sloan Kettering Cancer Center, New York, United States, ⁹Radiation Oncology, ¹⁰Pathology, Academic Medical Center, Amsterdam, Netherlands

Contact E-mail Address: r.j.coelen@amc.nl

Introduction: Endoscopic biliary drainage (EBD) and percutaneous transhepatic biliary drainage (PTBD) are both used to resolve jaundice prior to surgery for perihilar cholangiocarcinoma (PHC). PTBD has been associated with seeding metastases.

Aims & Methods: The aim of this study was to compare overall survival (OS), and the incidence of initial seeding metastases that potentially influence survival, in patients with preoperative PTBD versus EBD. Between 1991 and 2012, 278 patients underwent preoperative biliary drainage and resection of PHC at two institutions (Netherlands and USA). Of these, 33 patients were excluded for postoperative mortality. Among the 245 included patients, 88 patients who underwent preoperative PTBD (with or without previous EBD) were compared with 157 patients who underwent EBD-only. Survival analysis was done with Kaplan-Meier and Cox regression with propensity score adjustment.

Results: Unadjusted median OS was comparable between the PTBD group (35 months) and EBD-only group (41 months; P = 0.26). After adjustment for propensity score, OS between the PTBD group and EBD-only group was similar (Hazard ratio, 1.05; 95% CI, 0.74-1.49; P = 0.80). Seeding metastases in the laparotomy scar occurred as initial recurrence in 7 patients, including 3 patients (3.4%) in the PTBD group and 4 patients (2.7%) in the EBD-only group (P = 0.71). No patient had an initial recurrence in percutaneous catheter tracts.

Conclusion: The present study found no effect of PTBD on survival when compared to patients with EBD, and no increase in seeding metastases that develop as initial recurrence. These data suggest that PTBD can safely be used in preoperative management of PHC.

Disclosure of Interest: None declared

P0879 EVALUATION OF THE PREDICTORS OF SURGICAL SITE INFECTION AFTER HEPATECTOMY: A SINGLE-CENTER EXPERIENCE

T. Takayashiki¹, H. Shimizu¹, M. Ohtsuka¹, A. Kato¹, H. Yoshitomi¹, K. Furukawa¹, S. Takano¹, S. Kuboki¹, D. Suzuki¹, N. Sakai¹, S. Kagawa¹, M. Miyazaki¹

¹Department of General Surgery, Chiba university, Chiba, Japan

Contact E-mail Address: takayashiki@hospital.chiba-u.jp

Introduction: Surgical site infection (SSI) is the most common infectious complication after hepatectomy for hepato-biliary malignancies or hepatic benign lesions, with leading to longer hospital stays and higher medical costs. To clarify the predictors associated with SSI after hepatectomy, we conducted a retrospective cohort study of the patients who underwent hepatectomy at a single institution.

Aims & Methods: Recent 4 years, from June 2010 to June 2014, 430 patients underwent hepatic resection at our institution. Patient demographics, laboratory parameters, surgical records, and postoperative morbidity were evaluated and the predictors were identified using multivariate analysis between SSI group and non-SSI group.

Results: Of these 430 patients, 66 (15.3%) had SSIs after hepatectomy. 38 were men and 28 were women whose mean age was 66.6 years (range, 27 to 82). The most commonly disease and surgical procedure were hilar cholangiocarcinoma (n=25, 37.9%) and hemihepatectomy (n=32, 48.5%), respectively. The following pathogens were isolated by bacterial culture of purulent fluid from the patients of SSI; Enterococcus sp. (n=31), Staphylococcus sp. (n=17), Enterobacter sp. (n=3), and Klebsiella sp. (n=2), with high concordance of the bacterial culture from bile juice (70%). Postoperative hospital stays of SSI group (n=66) were significantly longer than that of non-SSI group (n=364). In a multivariate analysis, biliary reconstruction (odds ratio 6.24, 95% confidence interval 3.10-12.91, P < 0.001) and duration of operation (odds ratio 1.01, 95% confidence interval 1.00-1.01, P=0.01) were identified as independent predictors for SSI after hepatectomy.

Conclusion: Biliary reconstruction and duration of operation were independent predictors of SSI after hepatectomy. Bacterial infections of bile juice was one of the major source of SSI after hepatectomy.

Disclosure of Interest: None declared

P0880 LAPAROSCOPIC VERSUS OPEN REPAIR OF PERFORATED PEPTIC ULCER (PPU)

C. Lannerstad¹, S. Moradi¹, F. Frozanpor¹

¹Karolinska institutet, Dept of clinical sciences, Dept of Surgery, Danderyd Hospital, Stockholm, Sweden

Contact E-mail Address: carl.lannerstad@ds.se

Introduction: While open surgery for PPU has long been golden standard, laparoscopic repair is steadily increasing at Danderyd general hospital. Our hypothesis is, in this retrospective descriptive single-center study, that laparoscopic is superior to open repair.

Aims & Methods: All patients who underwent a primary surgical procedure for PPU from January 2011 to December 2014 were included. Our aim is to describe and compare the outcome of different surgical approaches regarding age, ASA, boey score, clavian-dindo and mortality.

Results: 67 patients were treated for PPU, 9 were excluded due to non-operative or endoscopic treatment. Repair was performed laparoscopically in 32 cases, open surgery in 26 among which 8 had been converted from initial laparoscopy. In 2 cases only a peritoneal lavage was performed and in another 2 cases lavage was performed and a duodenal stent was placed. Conversion from laparoscopy was due to adhesions, the size of the perforation or inability to locate it. No significant preoperative differences were found between the groups of patients who underwent open or laparoscopic repair concerning characteristics of patients or ulcer.

The mortality rate was highest among elderly and those with high ASA-scores. In the open repair group the Clavian-Dindo score, mortality and length of hospital stay were significantly higher.

Reoperation had to be performed in 6 cases, 4 for continued leakage, 1 for deep abscess and 1 for suture dehiscence.

	Laparoscopic N= 32	Open approach N=26	p
Male (n)	16	14	n.s
Age, yrs	63.0 (±19.3)	69.9 (±18.2)	n.s
ASA ≥3 (n)	15	16	n.s
General peritonitis (n)	22	16	0.59
Duodenal ulcer (n)	22	15	0.42
ICU-care (days, median)	2	8	0.016
In hospital (days)	5.5 ± 2.3	9.8 ± 8.0	0.04
Clavian-Dindo≥ 3a (n)	6	10	0.14
Abscess (n)	1	2	0.59
Reoperation (n)	4	2	0.40
Mortality (n)	2	7	0.05

Conclusion: The size and design of this study do not allow too strong conclusions despite the fact that significant differences were found for morbidity, mortality and length of hospital stay. Albeit not having found significant differences for preoperative status (ASA, boey score) several patients in the open repair group underwent open surgery because they were deemed unfit for laparoscopy. Either based on pulmonary disease or multi organ failure, it will bias the outcome between the groups to the advantage of the laparoscopic group. In conclusion, when feasable, laparoscopic repair for PPU seem to be beneficial for the postoperative care.

Disclosure of Interest: None declared

P0881 ENDOSCOPIC RETROGRADE CHOLANGIO-PANCREATICOGRAPHY IN THE HANDS OF HEPATOBILIARY SURGEON FOR MANAGMENT OF CHOLECYSTOCHOLEDOCHOLITHIASIS

E. A. Abdellatif¹, A. Elgeidie², E. Elhanafy¹, A. Elnakeeb¹, E. Gamal¹

¹General Surgery, Gastroenterology Surgical Center/Mansoura University, ²General Surgery, Gastroenterology Surgical Center, Mansoura, Egypt

Contact E-mail Address: dr.ehab.atif@gmail.com

Introduction: This study aims at assessment of the outcome of laparoscopic cholecystectomy (LC) with intraoperative endoscopic sphincterotomy (IOES) as a single session management option for patients with cholecysto-choledocholithiasis (CCL).

Aims & Methods: This is a retrospective analysis of the records and collected data for patients with CCL who were submitted for LC with IOES. Patients were preoperatively diagnosed by clinical presentation, laboratory findings, abdominal ultrasound examination, and magnetic resonance cholangiopancreatography (MRCP). IOES was performed after completion of LC and closure of ports in most cases. ERCP procedure was done by the surgeon with the patient is in the left lateral position.

Results: In the period between June 2009 to June 2013, 140 patients having combined (LC) and (IOES) for CCL were analyzed. One hundred and fourteen patients were females (82%). The mean age was 35.1 years. Mean serum bilirubin level was 7.5 mg/dl. Mean CBD diameter at MRCP was 9.1 mm and the mean CBDS size was 5.1 mm. Mean operation time was 87 minutes. Complete CBD clearance was possible in 134 patients (95.7%). The mean hospital stay was 3.1 days. There was no procedure related mortality. Complications were reported in 15 patients and included bleeding sphincterotomy (n=6; 4.3%), pancreatitis (n=7; 5%), and minor bile leak (n=2; %). All complications were treated by conservative means.

Conclusion: Combining IO-ERCP and sphinctrotomy with LC is a safe and effective single-session minimally invasive treatment strategy for patients with CCL that should be available in the hands of the experienced hepatobiliary surgeon.

Disclosure of Interest: None declared

P0882 SHORT-TERM OUTCOMES OF TOTALLY ROBOTIC ABDOMINOPERINEAL RESECTION FOR LOW RECTAL CANCER: A RETROSPECTIVE COMPARISON WITH LAPAROSCOPIC AND OPEN SURGERY

J. Xu¹, Y. Wei¹, L. Ren¹, Q. Feng¹, D. Zhu¹, J. Chen¹, W. Chang¹, Q. Lin¹

¹General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

Contact E-mail Address: xujmin@aliyun.com

Introduction: Currently, robotic surgery for rectal cancer using da Vinci System was common. However, few studies reported robotic approaches in abdominoperineal resections (APRs).

Aims & Methods: This study compared short-term outcomes of totally robotic, laparoscopic and open APRs for low rectal cancer. Between September 2013 and March 2015, a total of 231 consecutive patients received APRs were retrospectively engaged: 66 received totally robotic surgery as TRAP group, 89 received conventional laparoscopic surgery as LAP group, and 76 received open surgery as OS group. Short-term outcomes were analyzed, including length of recovery, quality of total mesorectal excision (TME), morbidity and mortality.

Results: The operating time of TRAP group (209.8 min) and LAP group (205.4 min) were almost the same (P=0.864), both longer than OS group (166.6 min, P < 0.001). TRAP group had less intraoperative hemorrhage, compared to LAP group (99.2 vs. 129.1 ml, P < 0.001) and OS group (99.2 vs. 141.6 ml, P < 0.001). TRAP resulted in shorter days to first flatus than LAP (1.6 vs. 2.3 days, P < 0.001) and OS (1.6 vs. 2.5 days, P < 0.001). Also, TRAP showed advantage in reducing days of retention catheterization after operation (TRAP vs. LAP, 2.3 vs. 3.3 days, P < 0.001; TRAP vs. OS, 2.3 vs. 3.1 days, P < 0.001). There was no difference among the three groups in open conversion rate, length of hospital stay after surgery, lymph node harvested, positive rate of circumferential resection margin or postoperative mortality. The morbidity rates were 16.7%, 28.1%, and 27.6% in the TRAP, LAP and OS groups respectively, with no significant difference. However, TRAP resulted in potentially less urinary retention than LAP (3.0% vs. 11.2%, P=0.059), and potentially less wound infection than OS (3.0% vs. 10.5%, P=0.082).

Conclusion: Totally robotic APRs were safe, and reproduce the equivalent TME quality of conventional laparoscopic and open surgery. Also, it provided less injury and faster functional recovery.

Disclosure of Interest: None declared

P0883 ROBOT-ASSISTED SIMULTANEOUS RESECTION OF COLORECTAL CANCER WITH LIVER METASTASES: A FEASIBLE AND INNOVATIVE TECHNIQUE

J. Xu¹, Y. Wei¹, X. Wang², W. Chang¹, Y. Peng², L. Ren¹, D. Zhu¹

¹General Surgery, ²Department of liver surgery, Zhongshan Hospital, Fudan University, Shanghai, China

Contact E-mail Address: xujmin@aliyun.com

Introduction: The Da Vinci Surgical System may help to overcome some of the difficulties of laparoscopy for complicated abdominal surgery. The aim of this study was to present an innovative technique that is robot-assisted, simultaneous radical resection of both colorectal cancer and liver metastasis (RSRCLM).

Aims & Methods: Between May 2013 and November 2014, we attempted to perform robot-assisted simultaneous resection of liver metastases in 24 patients with sigmoid colon cancer or rectal cancer. Procedure of this technique was described and clinic data of patients were collected and analyzed.

Results: We successfully completed the technique of RSRCLM in 24 patients with no conversions to an open procedure. The mean age was 55.1 ± 11.9 years and BMI (body mass index) was 22.9 ± 1.9 kg/m². The mean operation time was 293.3 ± 96.6 minutes and blood loss was 133.7 ± 105.4 ml. An R0 resection was achieved in all patientswith the minimal margin from 2mm to 35 mm. The aver age tumor size of colorectal cancer was4.7 ± 1.3 cm and that of metastatic liver tumor was 3.3 ± 1.9 cm. The aver age number of harvested lymph node was 20.7 ± 7.6. Patients were able to walk in first 2 days of surgery. The mean time get pass gas was 2.2 ± 0.5 days and flow eating start at 3.4 ± 0.9 days. The median duration for indwelling urine Foley catheter was 3.1 ± 1.2 days. The voiding function after removal of the urine Foley catheter was good (International Prostate Score Symptom (IPSS, 0–7) in 20 (83.3%) patients, fair (IPSS, 8–14) in three (12.5%), and poor (IPSS, 15–35) in one (4.2%).The mean postoperative hospital stay was 7.2 ± 2 days and hospital cost was 11325.5 ± 1337.6 US dollars. Overall morbidity and mortality was 8.3% and 0% respectively, within one month after surgery. At a median follow-up of 10 (range, 2-21) months, 23 (95.9%) patients remain disease-free.

Conclusion: This study shows that robot-assisted simultaneous resection is safe and technically feasible in selected patients with sigmoid colon cancer or rectal cancer liver metastases.

Disclosure of Interest: None declared

P0884 TRANSLATIONAL 3D-PRINTED ORGAN MANUFACTURING OF BIO-ELASTIC PATIENT-SPECIFIC ORGAN REPLICA FOR LAPAROSCOPIC SURGERY SIMULATION

M. Sugimoto¹

¹Gastroenterology, Kobe University, KOBE HYOGO, Japan

Contact E-mail Address: sgmt@med.kobe-u.ac.jp

Introduction: Professional 3D printers now incorporate photo-curable resins of various textures, transparency and flexibility. Before procedures, surgeons can now plan complex surgeries with MDCT scan data of a patient's bones, blood vessels or other organs, converted to a 3D-printable digital file (STL) that can be manipulated and studied. But these applications in the operating room are generally limited to a relatively small number of procedure types, though physicians can easily apply the lessons from one surgery to many others.

Aims & Methods: To overcome the limitation, we developed an anatomically accurate translational 3D-printed organ manufacturing system for surgical simulation. Our hybrid 3D imaging and 3D-printed injection molding technology allowed to manufacturing bio-elastic organ and abdominal wall replica.

Based on patient-specific DICOM data from MDCT, after generating its surface polygons using OsiriX application, the multi-material inkjet 3D printer created life-size copies of the 3D organs, blood vessels, and abdominal cavity. The replicas were manufactured bio-elastic by simultaneous jetting of different types of materials and injection molding the polyvinyl alcohol (PVA), which is a water-soluble synthetic resin. Each organ’s mold model was given an injection of a synthetic resin that helps make it feel wetter and more lifelike for the surgeon. We evaluated the feasibility of this system in 20 liver, pancreas, and kidney surgery simulations. We programed a printer to create clear models made from acrylic resins that allowed us to visualize and understand the hepatobiliary pancreatic complex internal structures and blood vessels or the exact tumor locations. We printed liver, pancreas, and kidney models compounding the polyvinyl alcohol (PVA) for tensile strength and elongation to break. It allowed these models realistic stand-in for ultrasonic diagnosis, hepatic intervention and surgical procedure such as cutting, suturing and ligation.

Results: The personalized bio-elastic wet organ replicas were useful for visible and tangible surgical simulation and navigation to plan and guide the successful liver, pancreas, and kidney surgeries. Such organ models can be soaked in water to look and feel closer to real organs. With the wet model, surgeons can experience the softness of organs and see them bleed, to help us in practice on lifelike models before stepping into real surgery. Using abdominal cavity replica, there was a place for using synthetic models in realistic surgical situation including laparoscopic surgery. The use of these replicas reduced the length of the operation and provided better anatomical reference tools for tailor-made navigation surgery, consequently helping to improve training for the operating room staff, students, and trainees.

Conclusion: The translation from 3D imaging to 3D manufacturing provided realistic surgical simulation of specific values of bio-texture in liver, pancreas, and kidney. The PVA was compatible for wet tissue simulation in ultrasonography and intervention in liver, pancreas, and kidney surgeries. These could overcome the limitations of the conventional image-guided navigation. Its combines the advantages of conventional 3D modeling and precise virtual 3D planning in personalized surgical simulation and navigation.

Disclosure of Interest: None declared

P0885 A PROSPECTIVE, RANDOMISED MULTICENTER STUDY COMPARING MINILAPAROTOMY CHOLECYSTECTOMY VERSUS LAPAROSCOPIC CHOLECYSTECTOMY WITH ULTRASONIC DISSECTION IN BOTH GROUPS – POSTOPERATIVE RECOVERY AT 4 WEEKS AFTER SURGERY

M. Kinnunen¹, S. Aspinen¹, J. Harju², P. Juvonen¹, H. Kokki³, M. Eskelinen¹

¹Surgery, Kuopio University Hospital/University of Eastern Finland, Kuopio, ²Surgery, Helsinki University Central Hospital, Helsinki, ³Anaesthesia and Operative Services, Kuopio University Hospital/University of Eastern Finland, Kuopio, Finland

Contact E-mail Address: maripk@student.uef.fi

Introduction: Cholecystectomy by minilaparotomy (MC) or by laparoscopy (LC) have been shown to have quite similar early recovery after surgery (Harju et al. 2013, 1). Monopolar electrosurgical energy is the most frequently used form of energy to achieve adequate dissection and haemostasis in the MC and in the LC. We assessed the MC with the ultrasonic dissection (UsD) versus the LC with the monopolar electrosurgical energy and our results suggested a shorter early recovery after surgery (Harju et al. 2013, 2). The outcome after the LC versus the MC with the UsD technique in both groups has not been compared in randomised trials. We therefore investigated the four weeks recovery after the LC and the MC with the UsD in 100 patients (ClinicalTrials.gov Identifier: NCT0172340).

Aims & Methods: Initially 100 patients with non-complicated symptomatic gallstone disease were randomized into the MC with the UsD (n=50) or the LC with the UsD (n=50) over a period of 2-years (2013-2015) and 95 of them (95%) were reached for a follow-up interview at four weeks after the surgery. Postoperative recovery at 4 weeks after surgery in the two study groups was assessed with a follow-up questionnaire to be filled and returned in a prepaid envelope, the non-responders were contacted by a phone. Analgesic efficacy was assessed with an 11-point numeric rating scale (NRS, 0 = no pain relief, 10 = total pain relief).

Results: Both groups were similar in terms of the demographic variables and surgical data. Postoperative data for the first four weeks after surgery were available for 95% of patients from both groups. The duration of postoperative pain (in days) was slightly shorter in the LC group, 8.5 (SD, 8.2) days, than in the MC group, 11.1 (SD, 10.8) days, (p=0.24). The mean length of sick leave was five days shorter in the LC group, 14.4 (SD, 10.3) days, than in the MC group, 19.9 (SD, 12.4) days, (p=0.05). The pain at normal activities after four weeks assessed with the NRS showed slightly lower scale values in the MC group, 0.3 (SD, 0.9) versus in the LC group, 0.6 (SD, 1.2), (p=0.23). Total use of analgesics after discharge (in days) was slightly shorter in the LC group, 6.6 (SD, 8.0) versus in the MC group, 7.7 (SD, 10.8), (p=0.59). The satisfaction with surgery was quite similar in the both study groups.

Conclusion: In conclusion, the cholecystectomy by minilaparotomy versus the cholecystectomy by laparoscopy with ultrasonic dissection in both study groups seems to have quite similar four weeks recovery after surgery. A new finding with the clinical relevance in the present work is the applicability of the UsD technique in the MC and the LC procedures.

Disclosure of Interest: None declared

P0886 MENTAL REHEARSAL WITH PATIENT SPECIFIC IMAGERY ENHANCES LAPAROSCOPIC SURGERY PERFORMANCE: A PILOT STUDY

M. Yiasemidou¹², D. Glassman¹, D. Miskovic²

¹Education and Simulation Hub, MidYorkshire Hospitals Trust, Wakefield, ²LIBACS, University of Leeds, Leeds, United Kingdom

Contact E-mail Address: marinayiasemidou@gmail.com

Introduction: Mental rehearsal of a task is known to improve performance in sports and music. Recent studies have shown some indications that it can do the same in surgery, with or without visual aids. Our study aims to assess the impact of mental rehearsal with interactive patient specific 3D imagery, on laparoscopic surgery performance.

Aims & Methods: 15 laparoscopic cholecystectomy novices were matched into two groups on 2:1 ratio. Group 1 (n=10) performed a simulated laparoscopic cholecystectomy on a virtual reality (VR) simulator after watching a didactic video of a real procedure. Group 2 (n=5) performed the same procedure after structured mental rehearsal with an interactive 3D visual aid. The optic tool was a 3D reconstruction of the relevant surgical anatomy (gallbladder, liver, cystic duct, cystic artery and peritoneal gathering), from an anonymised Computer Tomography. The anatomical features were modified to resemble the anatomy of the simulated model. Performance and safety variables were obtained from the VR simulator database after each procedure and compared between the two groups.

Results: Trainees who performed structured mental rehearsal using a 3D model prior to the operation had significantly less total number of movements (Group 2 median 553, Group 1 1391.5, p=0.005) and total path length of instrument tip (Group 2 mean 1540.24, Group 1 mean 2837 p=0.007). Furthermore, trainees in group 2 performed the procedure significantly faster than the trainees in Group 1 (Group 2 median 667s, Group 1 mean 1283, p=0.003). There was no statistical difference in the safety metrics (number of perforations p=0.07, non-cauterised bleeding p=0.114, damage to vital structures p=0.529).

Conclusion: From this pilot data there are strong indications that viewing a patient-specific 3D model of the relevant anatomy can enhance surgical performance.

Disclosure of Interest: None declared

P0887 LAPAROSCOPIC BASIC SKILLS TRAINING - BLACK BOX OR HIGH FIDELITY SIMULATORS ?

N. Oussi¹², C. Loukas³, L. Henningsohn²⁴, A. Kjellin², E. Georgiou³, L. Enochsson¹²

¹Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, ²Center for Advanced Medical Simulation and Training, Karolinska University Hospital, Stockholm, Sweden, ³Medical Physics Laboratory and Simulation Center, Medical School, University of Athens, Athens, Greece, ⁴Division of Urology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden

Contact E-mail Address: lars.enochsson@ki.se

Introduction: Training in laparoscopic high-fidelity simulators to proficiency levels has been shown to improve laparoscopic cholecystectomy skills (1-3). However, since high-fidelity laparoscopic simulators are expensive the availability is limited which could have a negative impact on the opportunity of laparoscopic training for residents. In countries with a strained economy other priorities within the health sector than buying expensive simulators are made. In countries with a somewhat better economy but with large distances to travel, residents working in or near large academic centers often have a much better access to simulator training. Whether laparoscopic basic skills training in black boxes can be an adequate alternative to corresponding basic skills training in high fidelity simulators for students and residents in this high-tech era is not known.

Aims & Methods

Aim: To analyze how basic skills training in a black box or a high fidelity simulator (LapMentor, Simbionix, USA) motivated medical students and if differences in surgical skills performance were noted when tested in a validated surgical simulator (MIST, Mentice, Sweden).

Methods: Medical students (n=57) during their surgical semester volunteered to participate in the study. After signing informed consent the students completed a questionnaire regarding their expectations of the simulation training. Their visuospatial ability was also tested. They were then randomized into either basic skills training in a black box (n=31) or in the LapMentor (n=26). Following their skills training all the students did three tests in the validated MIST simulator (1) and then finally they completed a questionnaire of how they had experienced the simulator practice sessions regarding how they liked it, if it facilitated their MIST performance and if it had been difficult.

Results: Students training in both the BlackBox and the LapMentor found that the training exceeded their expectations regarding how well they thought that they would like it.

BlackBox estimations increased from an expectation level of 73.1% pre-training on the VAS scale to 80.0% post-training (P=0.0365) and LapMentor from 75.8% pre-training to 82.2% post-training (P=0.0225). There was a significant correlation in the BlackBox group between how difficult they experienced the simulation training was and their MIST-performance (RSquare=0.25; P=0.0064). There was also a positive trend towards how well they thought that the BlackBox training facilitated their MIST-performance (RSquare=0.10; P=0.0953). In the LapMentor group no such correlations existed (RSquare=0.02; P=0.61 “Was difficult” and RSquare=0.00; P=0.92 “Facilitated"). More students in the BlackBox group also completed the MIST excercises (28 vs. 19).

Conclusion: The perhaps more straightforward approach to basic skills training procedures in the low-tech BlackBoxes seems to correlate better with MIST performance. The results indicate a still important role for low-tech and low-cost BlackBoxes in laparoscopic basic skills training of students in an otherwise high-tech surrounding.

Disclosure of Interest: None declared

P0888 T4 COLON CANCER: AN ABSOLUTE CONTRAINDICATION TO LAPAROSCOPIC RESECTION?

S. Arolfo^1,*, M. E. Allaix¹, M. Mistrangelo¹, A. Arezzo¹, M. Morino¹

¹Department of Surgical Sciences, University of Torino, Torino, Italy

Contact E-mail Address: meallaix@gmail.com

Introduction: Some retrospective comparative studies have shown that laparoscopic resection (LR) of T4 colon cancer is feasible and oncologically adequate, but it is burdened by high conversion rates to open resection (OR). The selection criteria for the laparoscopic approach to T4 colon cancers are unclear.

Aims & Methods: The aim of this study was to identify possible tumor-related factors that should be considered as contraindication to LR in T4 colon cancer patients. The short-term and the long-term oncologic outcomes of LR or OR were also evaluated.

It is a retrospective analysis of a prospectively collected database. All patients undergoing elective LR or OR for non-metastatic T4 colon cancer were included. Statistical analyses were performed on an ‘‘intention-to-treat’’ basis and by actual treatment. Kaplan-Meier curves were compared to analyse overall survival (OS) and disease-free survival (DFS).

Results: OR and LR were performed for T4 colon cancer in 50 and 48 patients, respectively. A complete R0 resection was obtained in 49 (98%) OR and in 48 (100%) LR patients (P=0.962). Conversion to open surgery occurred in 12 LR patients (25%), due to a tumor larger than 6 cm (75%) or the need for a multi-visceral resection (25%). There was a trend towards a higher rate of 30-day morbidity after OR than LR (34% vs. 16.7%; P=0.083). Thirty-day mortality rate was similar after OR and LR: 4% vs. 0% (P=0.495). Median postoperative length of stay was longer after OR, than converted resection or LR: 12 (range, 7-60) vs. 9 (range, 6-14) vs. 7 (range, 5-51) days (P=0.005). No significant differences were observed in the median number of lymph node harvested after OR or LR: 16 (range, 6-29) vs. 14 (range, 7-36), P=0.455. Median follow-up was 46.5 (range, 3-140) months for OR patients and 37 (range, 6-139) months for LR patients (P=0.274). Five-year OS and DFS did not differ significantly between OR and LR patients: 66.7% vs. 65.8% (P=0.828), and 59.7% vs. 58.6% (P=0.634). Conversion to OR did not affect OS and DFS.

Conclusion: LR is associated with a high conversion rate to OR. Patients with a tumor larger 6 cm and/or infiltrating adjacent organs should be treated by OR. In selected cased, LR for T4 colon cancer has better short-term outcomes and similar oncologic outcomes compared to OR.

Disclosure of Interest: None declared

P0889 PAN-EUROPEAN SURVEY ON LAPAROSCOPIC PANCREATIC SURGERY

T. De Rooij¹, M. G. Besselink¹, A. Shamali², G. Butturini³, O. R. Busch¹, B. Edwin⁴, R. Troisi⁵, L. Fernández-Cruz⁶, B. Topal⁷, I. Dagher⁸, C. Bassi³, M. Abu Hilal⁹, on behalf of DIPLOMA trial group

¹Department of surgery, Academic Medical Center, Amsterdam, Netherlands, ²Department of surgery, Southampton University Hospital NHS Foundation Trust, Southampton, United Kingdom, ³Department of surgery, University of Verona Hospital Trust, Verona, Italy, ⁴Department of surgery, Oslo University Hospital, Oslo, Norway, ⁵Department of surgery, University Hospital of Ghent, Ghent, Belgium, ⁶Department of surgery, Hospital Clinic University of Barcelona, Barcelona, Spain, ⁷Department of surgery, Leuven University Hospital, Leuven, Belgium, ⁸Department of surgery, Antoine Béclère Hospital, Paris-Sud University, Paris, France, ⁹Department of surgery, Southampton University Hospital NHS Foundation Trust, Southampton, Netherlands

Contact E-mail Address: t.derooij@amc.nl

Introduction: Benefits of minimally invasive pancreatic surgery, especially for cancer, are under debate since no randomized studies have been performed. It is unclear which proportion of pancreatic resections (pancreatoduodenectomy, distal pancreatectomy) is currently performed via a minimally invasive approach and whether these procedures are performed for cancer.

Aims & Methods: An online survey, consisting of 30 questions, was sent to the members of the European Pancreatic Club, the European-African Hepato-Pancreato-Biliary Association and to 5 national pancreatic societies in Europe between June and December 2014. Non-responders received two reminders. Fully completed responses were included. Because of overlapping, confidential membership lists, the number of invitees was unknown.

Results: In total, 237 pancreatic surgeons responded. After excluding 34 for incomplete responses, 203 responses from 27 European countries were analysed. 164 (81%) surgeons were employed at a university hospital, 184 (91%) performed advanced minimally invasive surgery, 148 (73%) performed minimally invasive distal pancreatectomy. Minimally invasive pancreatoduodenectomy was performed by 42 (21%) surgeons whereas only 9 surgeons had performed more than 10 of these procedures. Robot-assisted pancreatic surgery was performed by 28 (14%) surgeons. 63 (31%) surgeons expected minimally invasive distal pancreatectomy for cancer to be inferior to open distal pancreatectomy concerning oncological outcomes. 151 (74%) surgeons expected to benefit from training in laparoscopic distal pancreatectomy and 149 (73%) were willing to participate in a randomized trial on this topic.

Conclusion: Minimally invasive distal pancreatectomy has become a common surgical procedure, although its benefits for cancer are under debate. Minimally invasive pancreatoduodenectomy has not yet been implemented. Specific training in laparoscopic distal pancreatectomy is welcomed and a pan-European randomized controlled trial for pancreatic cancer (DIPLOMA) seems indicated.

Disclosure of Interest: None declared

P0890 CLINICAL OUTCOMES AFTER ENDOSCOPY-ASSISTED LAPAROSCOPIC FULL-THICKNESS RESECTION FOR SUPERFICIAL DUODENAL NEOPLASMS

Y. Minato¹, K. Ohata¹, M. Murakami², K. Yamazaki², Y. Misumi¹, H. Tsunashima¹, E. Sakai¹, T. Muramoto¹, Y. Matsuyama¹, M. Takita¹, T. Tashima¹, K. Nonaka¹, N. Matuhashi¹

¹Gastroenterology, NTT Medical Center Tokyo, ²Gastroenterological and General Surgery, Showa University Hospital, Tokyo, Japan

Contact E-mail Address: yoieiminato55925@gmail.com

Introduction: Superficial duodenal neoplasms (SDNs) are rare, but clinically important disease, whereas whose therapeutic strategies have not been established. Endoscopic resection is technically difficult, due to thin intestinal walls which can be easy to perforated and difficulty of maneuvering endoscope. On the other hand, surgical resection seemed considerably invasive. In addition, it is often difficult to recognize the extent of the lesion precisely during surgical approach. To overcome these problems, we developed a noble approach to treat SDNs which involves a combination of endoscopic and laparoscopic techniques; endoscopy-assisted laparoscopic full-thickness resection (EALFTR).

Aims & Methods: The aim of this study was to assess the clinical outcomes after EALFTR for SDN. Between January 2011 and March 2015, a total of 85 patients with 90 non-amupllary SDNs were enrolled in this study. Patients with familial polyposis syndrome were excluded. Clinocopathological characteristics (e.g. age, sex, tumor location and size) were collected at initial endoscopic examination. The primary outcome was en-bloc R0 resection rate. Secondary outcomes were procedure time, complications and length of hospital stay after EALFTR. Moreover, long-term outcomes of SDNs after EALFTR were also evaluated. EALFTR procedure was previously described in our report. In summary, subsequent to the laparoscopic duodenal mobilization, peripheral margin was marked around the tumor endoscopically and each marking was perforated intentionally using a needle knife in the coagulation mode.After laparoscopic full-thickness incision, closure of the defect in the duodenal wall was performed by a laparoscopic hand-suturing technique.

Results: Lesions were predominately located at the second portion (50/90, 56%), whereas others located at bulb (32/90, 35.6%) and third portion (8/90, 8.9%), respectively. The tumor size was 13.2 ±11.6 mm, and the resected specimen size was 26.0 ±10.5 mm. The mean procedure time was 146 ±43.2 minutes. The mean length of hospital stay after EALFTR was 11.6 ±6.7 days. Although two of 90 cases were converted to open surgery, en-bloc R0 resection was achieved in most of remaining cases (86/88, 98%). Regarding to complications, postoperative anastomotic leakage and stenosis occurred in three (3.5%) and five patients (5.9%), respectively, however all patients recovered conservatively. Histopathological examination confirmed 42 adenomas, 22 adenocarcinomas, 17 neuroendocrine tumors, and 9 others. Of 71 patients whose follow-up period longer than 1 year, no metastasis and/or local recurrence was detected during the median follow-up period of 27 months (range, 12 – 44).

Conclusion: We confirmed favorable clinical outcomes of EALFTR for SDNs. EALFTR enables successful en-bloc R0 resection, with minimally invasive manner. Our results indicated that EALFTR hardly concerns with tumor dissemination. We believe EALFTR can be a effective treatment option for SDNs, although great caution against complications is mandatory.

Disclosure of Interest: None declared

TUESDAY, OCTOBER 27, 2015   09:00-17:00

IBD II – HALL 7__________

P0891 NATURAL PEPTIDE INHIBITOR OF NEUTRAL ENDOPEPTIDASE (NEP) ALLEVIATES EXPERIMENTAL COLITIS IN MICE AFTER SYSTEMIC ADMINISTRATION

H. Zatorski¹, M. Salaga¹, M. Sobocinska², E. Kamysz², J. Fichna¹

¹Department of Biochemistry, Medical University of Lodz, Lodz, ²Laboratory of Biological Macromolecules Chemistry, Department of Molecular Biotechnology, University of Gdansk, Gdansk, Poland

Contact E-mail Address: zatorski.h@gmail.com

Introduction: The role of endogenous opioid peptides in the pathophysiology of inflammatory gastrointestinal (GI) disorders is widely recognized, but poorly understood. This is, among others, because of the short half-life of these peptides, which are quickly inactivated by endopeptidases, e.g., neutral endopeptidase (NEP, EC 3.4.24.11). NEP inactivates endogenous Met- and Leu-enkephalins, which are potent regulators of GI motility, secretion and pain sensation, acting through μ, κ and δ opioid receptors (MOR, KOR and DOR, respectively).

Aims & Methods: The aim of this study was to investigate the effect of the natural peptide inhibitor of NEP, sialorphin and Met- and Leu-enkephalins in mouse models of experimental colitis.

Methods: To assess the anti-inflammatory activity of tested compounds, we used acute and semi-chronic models of inflammation induced by intracolonic administration of TNBS as well as acute model of DSS-induced colitis. Body weight, macroscopic score, ulcer score, colon length, weight and thickness were recorded. Moreover, in all experiments the level of myeloperoxidase (MPO) activity was determined as an indicator of neutrophil infiltration in colonic tissue. In order to determine the mechanism of action of sialorphin, we used selective MOR, KOR and DOR antagonists; β-funaltrexamine (β-FNA), nor-binaltorphimine (norBNI) and naltrindole (NLTR), respectively.

Results: Met- and Leu-enkephalin and sialorphin administered intraperitoneally (i.p.) at the dose of 1 mg/kg twice daily significantly ameliorated colitis in the acute model, as indicated by reduced macroscopic and ulcer scores, as well as bowel length and thickness and MPO activity. In addition, the anti-inflammatory activity of sialorphin was dose-dependent at the dose range from 0.3 to 3 mg/kg (i.p., twice daily). The therapeutic effect of sialorphin (1 mg/kg, i.p. twice daily) in the acute model was blocked by selective MOR and KOR, but not DOR antagonists (all at a dose of 1 mg/kg i.p.). In the semi-chronic model of TNBS-induced colitis sialorphin (1 mg/kg, i.p.) partially improved macroscopic parameters of the disease but this effect was not statistically significant. Interestingly, treatment with sialorphin had no effect in the model of DSS-induced colitis.

Conclusion: We propose a novel anti-IBD therapeutic strategy, based on the treatment with inhibitors of enkephalin-degrading enzymes and the elevation of endogenous enkephalin levels.

Disclosure of Interest: None declared

P0892 IS INTESTINAL DYSBIOSIS A FACTOR LEADING TO COLONIC INFLAMMATION?

M. Aguilera¹, J. Estévez¹, V. Martinez¹

¹Cell Biology, Physiology & Immunology, Universidad Autonoma de Barcelona, Bellaterra - Barcelona, Spain

Contact E-mail Address: vicente.martinez@uab.es

Introduction: Dysbiotic states have been associated to intestinal inflammation. However, a causal relationship has not been established and it is not clear if dysbiosis should be regarded as a cause or a consequence of intestinal inflammation. To further understand the relationship disbiosis-inflammation we assessed immune activation and the appearance of colitis in mice subjected to antibiotics-induced dysbiosis.

Aims & Methods: A dysbiotic state was induced with a 1-wk or 2-wk duration oral treatment with non-absorbable, broad spectrum antibiotics (bacitracin and neomycin) in mice. At the end of the treatment, colonic luminal and wall adhered microbiota (fluorescent in situ hybridization and qPCR), inflammatory markers (RT-qPCR) and macroscopical and microscopinal signs of colonic inflammation were assessed.

Results: 1-wk or 2-wk antibiotic treatment resulted in a similar dysbiotic state; with an increase in the proportion of Lactobacillus spp, Bifidobacterium spp and coccoid forms of Clostridium cluster XIVa. However, total bacterial counts were reduced during a 1-wk treatment (by 50% vs. control conditions, P < 0.05), while there was a 2-fold increase during the 2-wk treatment (P < 0.05 vs. control). During a 1-wk treatment, bacterial adherence to the colonic epithelium was favored, while no changes were observed during the 2-wk treatment. A local immune activation, as seen by an increase in the luminal levels of secretory IgA (Table) and the up-regulation in the expression of antimicrobial peptides was observed. Although these changes, no macroscopical (except for an enlargement of the cecum) or microscopical signs of colonic inflammation were observed (see Table).

Table: Immune activation and macro and microscopic changes in the colon during antibiotic treatment (Data are mean ± sem, 6-16 animals per group; *: P < 0.05 vs. respective vehicle control.)

	Secretory IgA (mg/ml)	Weight cecum (mg)	Colon relative weight (mg/cm)	Histopathological score (0-12)
Vehicle 1-wk	7.2 ± 1.4	318.4 ± 16.5	12.6 ± 0.7	1.6 ± 0.4
Antibiotics 1-wk	261.7 ± 6.5 *	661.9 ± 16.5 *	14.8 ± 0.9	1.8 ± 0.6
Vehicle 2-wk	36.7 ± 11.5	409.0 ± 20.2	23.3 ± 1.8	0.7 ± 0.2
Antibiotics 2-wk	362.5 ± 11.5 *	507.7 ± 18.4 *	23.9 ± 1.9	1.3 ± 0.2

Conclusion: Colonic dysbiosis might result in a state of “low grade inflammation", characterized by a local immune activation in the absence of structural changes. Similar states (disbiosis and low-grade inflammation) are described in patients with functional gastrointestinal disorders, mainly irritable bowel syndrome. Dysbiosis seems to represent a contributing factor to immune colonic responses but, per se, does not result in an overt inflammatory reaction.

Disclosure of Interest: None declared

P0893 EXOSOME: A NEW MEDIATOR OF HOST RESPONSE TO CROHN’S DISEASE-ASSOCIATED ADHERENT-INVASIVE ESCHERICHIA COLI

J. Carriere¹, A. Bretin¹, N. Barnich¹, A. Darfeuille-Michaud¹, H. T. T. Nguyen¹

¹M2iSH UMR 1071 Inserm/University of Auvergne, Clermont-Ferrand, France

Contact E-mail Address: Jessica.CARRIERE@udamail.fr

Introduction: Crohn’s disease (CD) is a chronic inflammatory bowel disease of which the etiology involves environmental, genetic and microbial factors. A high prevalence of invasive Escherichia coli strains, named AIEC (adherent-invasive E. coli), has been reported in the intestinal mucosa of CD patients. Exosomes are small endosomal-derived vesicles involved in cell to cell communication and have been implicated in various diseases including cancer and infectious disorders.

Aims & Methods: Here, we investigated the potential involvement of exosomes in host response to AIEC infection. Exosomes were extracted from human intestinal epithelial T84 cells and human monocyte-derived THP-1 macrophages uninfected or infected with the AIEC reference strain LF82 or the non-pathogenic K-12 C600 strain by using the ExoQuick exosome precipitation kit (System Biosciences). Epithelial permeability was assessed by measuring the TER and the translocation of FITC 4kDa. Intracellular number of AIEC was determined by using the gentamicine protection assay.

Results: Electron microscopy showed that infection with AIEC LF82 increased the release of exosome-like microvesicles of 30-100nm from T84 and THP-1 cells. Immunogold labelling and Western blot analyses confirm the presence of the well-known exosomal marker CD63 in these microvesicles. Characterization of exosomes released from LF82-infected cells showed that they did not affect either intestinal epithelial permeability, or adhesion and invasion capacity of AIEC LF82 in T84 cells, or expression of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6)-host epithelial receptor for AIEC. However, compared to exosomes released from non-pathogenic K12-infected host cells, those from LF82-infected cells induced in naïve recipient cells increased activation of NF-kappaB and MAPK pro-inflammatory signaling pathways and enhanced production of pro-inflammatory chemokines and cytokines IL-8, TNF-α and IL-6. In contrast, exosomes released from uninfected cells did not exhibit these pro-inflammatory activities. Mass spectrometry analysis revealed that exosomes released from LF82-infected T84 cells carried microbial antigens including the outer membrane protein C (OmpC), a known virulence factor of AIEC bacteria.

Conclusion: In conclusion, our study shows that in response to CD-associated AIEC infection, intestinal epithelial cells and macrophages release exosomes that can trigger pro-inflammatory responses in naïve macrophagic recipient cells.

Disclosure of Interest: None declared

P0894 ACTIVATION OF WNT SIGNALLING BY M2A MACROPHAGES PROMOTES MUCOSAL REPAIR IN MURINE IBD

J. Cosin-Roger¹, D. Ortiz-Masiá¹, D. C. Macias-Ceja¹, S. Calatayud¹, C. Hernández¹, J. Hinojosa², M. D. Barrachina¹

¹Pharmacology, Faculty of Medicine, University of Valencia, ²Hospital Manises, Valencia, Spain

Contact E-mail Address: jesus.cosin@uv.es

Introduction: Mucosal repair is a key goal in Inflammatory Bowel Disease (IBD) treatment and the Wnt signalling pathway plays a crucial role in this process. Macrophages coordinate tissue repair and expression of canonical Wnt ligands has been associated with the M2 phenotype. Recent studies reported an impaired M2 polarization and delayed wound healing in STAT6-/- mice.

Aims & Methods: We aim to evaluate the role of STAT6 in Wnt ligands expression associated with M2 polarization in vivo and the relevance of these cells in wound healing in a murine model of colitis. Peritoneal macrophages were isolated from WT and STAT6-/- and polarized towards M1 and M2 phenotype. mRNA expression of canonical Wnt ligands was analyzed by qPCR (fold induction). Colitis was induced in STAT6-/- by an intrarectal injection of TNBS (3.5mg/20g mice) and 2 days later received an i.p. injection of macrophages (2·10⁶ million) obtained from WT and STAT6-/- treated with Il-4 (WT-M2a and STAT6-M2a, respectively). Mice were weighed daily (percentage of body weight at day 4 vs day 0). 4 days after TNBS were sacrificed, colon length was measured and mucosal histology was evaluated according to Wallace Score. Mucosal expression of iNOS, TNFα, IL-1β, c-myc and Lgr5 was analyzed by qPCR and protein levels of nuclear β-catenin by western blot. Data are expressed as Mean ± SEM (n ≥ 5).

Results: In peritoneal macrophages from WT mice we detected the expression of Wnt2b, Wnt7b, Wnt10a and Wnt10b, while Wnt1, Wnt3a and Wnt6 were not detected. In macrophages obtained from WT mice, polarization towards the M2a phenotype induced a significant increase in the expression of Wnt2b (4.0 ± 1.1) and Wnt7b (2.8 ± 0.3) compared with that detected in non-polarized (1.1 ± 0.2 and 1.1 ± 0.2) and M1 macrophages (1.1 ± 0.4 and 0.8 ± 0.2). However, in macrophages obtained from STAT6-/- mice and polarized towards M2a phenotype the expression of Wnt2b (0.9 ± 0.2) and Wnt7b (0.9 ± 0.3) was not significantly different to that detected neither non-polarized (1.3 ± 0.2 and 0.9 ± 0.2, respectively) nor M1-macrophages (0.9 ± 0.4 and 1.1 ± 0.1, respectively). In STAT6-/- mice treated with TNBS, administration of WT-M2a macrophages accelerated the regain of body weight (98.1 ± 0.6%) compared with the administration of STAT6-M2a macrophages (92.9 ± 1.1%). These cells also enhanced the functional recovery of mice since colons from mice treated with WT-M2a macrophages were significantly longer and exhibited less histological damage score than those colons from mice with STAT6-M2a macrophages. The mRNA expression of pro-inflammatory markers such as iNOS, TNFa and IL-1b was significantly lower in the mucosa of mice treated with WT-M2a macrophages (0.7 ± 0.1, 0.5 ± 0.1 and 0.6 ± 0.2, respectively) than in that of mice treated with STAT6-M2a macrophages (1.0 ± 0.1, 1.1 ± 0.1 and 1.0 ± 0.1, respectively). A significant increase in nuclear b-catenin (1.6 ± 0.1) and mRNA expression of two Wnt target genes, c-myc (1.6 ± 0.2) and Lgr5 (2.1 ± 0.4) was detected in the mucosa of mice treated with WT-M2a macrophages compared whith that of mice with STAT6-M2a macrophages (1.0 ± 0.1, 1.1 ± 0.1 and 1.1 ± 0.1, respectively).

Conclusion: STAT6 mediates the expression of canonical Wnt ligands associated with the M2a macrophage phenotype. Activation of Wnt signalling by a STAT6-dependent macrophage phenotype promotes mucosal repair in murine IBD.

Disclosure of Interest: None declared

P0895 ACTIVATION OF COLONIC AUTOPHAGY WITH TREHALOSE IMPROVES WOUND HEALING IN MURINE COLITIS

J. Cosin-Roger¹, D. Ortiz-Masia¹, D. C. Macias-Ceja¹, P. Salvador¹, S. Calatayud¹, C. Hernández¹, M. D. Barrachina¹

¹Pharmacology, Faculty of Medicine, University of Valencia, Valencia, Spain

Contact E-mail Address: jesus.cosin@uv.es

Introduction: Autophagy plays a homeostatic role in intestinal epithelial cells by engulfing intracellular organelles and endogenous pathogens leading to the degradation of their contents. Several polymorphisms in gene loci containing autophagy-related proteins such as ATG16L1, IRGM, and NOD2 have been associated with an increased risk of Crohn`s disease and it has been suggested that a defective autophagy may have a role in its pathogenesis.

Aims & Methods: We aim to analyze the expression of autophagic protein markers in a murine model of colitis induced by TNBS and the resultant effects of activating mucosal autophagy on the course of the disease. Mice received an intrarectal injection of TNBS (3.5mg/20g) in order to induce colitis and control animals received an intrarectal injection of TNBS-vehicle (EtOH 40%) (day 0). Some mice received trehalose in the drinking water (3%) during three weeks before TNBS administration. After colitis induction, changes in body weight were determined daily (results are expressed as percentage vs the weigth at day 0) and mice were sacrificed 2 and 4 days after TNBS administration. Mucosal histology was evaluated after an hematoxylin staining according to Wallace Score (1-10). Colons were frozen for protein extraction and Western blot experiments of p62, LC3 and b-actin were performed. Data are expressed as Mean ± SEM (n ≥ 5).

Results: Treatment of mice with TNBS induced a loss of body weight that peaked 2 days after treatment. Subsequently, mice began to recover and, four days after treatment, body weight reached similar values to those of control animals. The expression of autophagic protein markers reveal a slight accumulation of both p62 and LC3II protein levels in the mucosa of TNBS-treated mice compared with the control mucosa, suggesting a reduction in the autophagic flux in the inflamed mucosa, which was observed 2 and 4 days after TNBS. Chronic treatment with trehalose induced a significant increase in LC3II protein levels and a significant decrease in p62 protein levels in the colonic mucosa of both control and TNBS-treated mice showing that trehalose was increasing the autophagic flux in both conditions. In trehalose-treated mice, the loss of body weight was significantly lower at day 1 and 2 (92.85 ± 1.28 and 96.48 ± 1.42, respectively) compared with that observed in vehicle-treated mice (90.24 ± 0.76 and 91.33 ± 1.72, respectively). The analysis of histological damage score revealed significant differences between trehalose (4.3 ± 0.4) and vehicle-treated mice (5.5 ± 0.6), four days after TNBS administration.

Conclusion: Chronic treatment with trehalose during three weeks activates autophagy in murine colonic mucosa and improves wound healing and functional recovery of TNBS-treated mice.

Disclosure of Interest: None declared

P0896 RESPONSE TO CORTICOSTEROIDS IN ULCERATIVE COLITIS MAY BE RELATED TO MODULATION OF MTOR SIGNALING PATHWAY GENES BY MICRORNAS

J. E. Naves¹, J. Manye¹², V. Loren¹, M. Mañosa³, I. Moret⁴, A. Garcia-Jaraquemada¹, A. Aransay²⁵, G. Bastida²⁴, B. Beltrán²⁴, E. Cabré²³, E. Domènech²³

¹Gastroenterology Department, Fundació Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, ²Ciber, Madrid, ³Gastroenterology Department, Hospital Universitari Germans Trias I Pujol, Badalona, ⁴Gastroenterology Department, La Fe Hospital, Valencia, ⁵CIC Biogune, Bizkaia, Spain

Contact E-mail Address: navesjuan@gmail.com

Introduction: Mechanisms of resistance to corticosteroids (CS) in ulcerative colitis (UC) are not well understood. Little is known about the influence of microRNAs (miR) in the response to CS in UC.

Aims & Methods

Aims: To compare the transcriptomic profile in rectal mucosa of patients with active UC responding and non-responding to CS.

Methods: Rectal biopsies were obtained from UC patients before and after three days of CS treatment. Patients were grouped in responders and non-responders according to Montreal’s classification. miR were identified by means of a sequencing method (Illumina) and RNAm were study by microarrays method (Illumina) on those rectal biopsies with high integrity. Those miR and RNAm with a fold change ≥ 1.5 and adjusted p-value ≤ 0.05 were further studied.

Results: 32 out of 48 tissue samples reached an integrity that allowed miR sequencing or microarrays study. Comparison between groups showed a differential miR expression of miR-1246, miR-1291, miR-5701 and miR-625-3p, miR-183-5p, miR-3607-3p, miR-4770, miR-449, miR-145-3p. The only gene with differential expression after microarrays study was DDIT4. In silico study reveals that DDIT4 is a potential target of three of the differential expressed miR (miR-183-5p, miR-625-3p, miR-3607-3p) and also that this gene is linked to the mTOR pathway (and indirectly with autophagy).

Conclusion: There is a different profile of rectal microRNAs between responders and non-responders to CS. Our findings suggest that regulation of mTOR and autophagy pathways by miR might be involved in the response to CS in active UC.

Disclosure of Interest: None declared

P0897 ULCERATIVE COLITIS PATIENTS AND THE FAMILY’S ENTEROBACTERIA BUSH COMPARATIVE INVESTIGATION

K. Fukuda¹, Y. Fujita¹

¹Gastroenterology, St Luke’s International Hospital, Tokyo, Japan

Contact E-mail Address: fukukats@luke.ac.jp

Introduction: The role of intestinal microflora in the aetiology of inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease is broadly assumed. The Terminal Restriction Fragment Length Polymorphism (T-RFLP) is a molecular biology technique for profiling microbial communities in faecal samples. We have recently reported the application of T-RFLP to validate the discriminant score of intestinal microbiota as a biomarker of disease activity in patients with UC. However, because T-RFLP cannot distinguish specific bacterial strains, it is not the best technique when one wishes to trace IBD among family members.

Aims & Methods: In the present study, instead of T-RFLP, we were interested to apply the Amplicon Sequence analysis to the intestinal flora in faecal samples from UC patients and patients’ relatives as a molecular biology probe. The subjects were 90 patients with UC together with 78 relatives of the same UC patients as a control group. Twenty-seven patients had active UC (group I) and 63 had quiescent UC (group II). The later included 31 with mild inflammation in the large intestine (group IIa), and 32 without inflammation (group IIb). The patients’ relatives were consanguineous (group III, n=45), and non-consanguineous (group IV, n=33). With the Amplicon Sequence analysis, intestinal microflora in faecal samples from 78 relatives and from the 90 patients with UC were analysed for comparative interpretations. The software we used was an SPSS (IBM Statistics 20.0).

Results: With the technology we applied, it was possible to identify over 600 different bacterial species and analyse quantitatively. Among all groups, Bifidobacterium did not show significant difference. Bacteroides, especially Fragilis and Enterobacteriaceae were markedly increased in patients with active UC. In contrast, Verrucomicrobiales species were markedly decreased in patients with active UC.

Conclusion: The most significant findings of this study include a marked increase in the Bacteroides, Fragilis and Enterobacteriaceae during active UC, while the Verrucomicrobiales species were markedly decreased in active UC patients. Further, in several previously studies, Bifidobacterium has been reported to be decreased in patients with active UC, but we did not find any clinically relevant change in Bifidobacterium in this study. The present method could reveal presence of pathologic as well as beneficial bacterial strains in IBD patients. We believe that further studies including more factors for analyses are warranted to better understand the significance of intestinal microflora in the immunopathogenesis of IBD.

Disclosure of Interest: None declared

P0898 DUAL OXIDASE 2, A NOVEL PLAYER IN INFLAMMATORY BOWEL DISEASE: EXPRESSION AND FUNCTIONAL IMPLICATIONS

K. M. Rabinoiwtz¹, L. Reshef², H. Elad¹, U. Gophna², I. *Dotan¹³

¹IBD Center Gastroenterology and Liver Diseases and The Research Center for Digestive Tract and Liver Diseases, Tel Aviv Medical Center, ²Molecular Microbiology and Biotechnology, ³Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Contact E-mail Address: kerenra@tlvmc.gov.il

Introduction: Inflammatory bowel diseases (IBD) are comprised of Crohn's disease (CD) and ulcerative colitis (UC). Unlike the inflammation in CD that can affect any part of the bowel, inflammation in UC is limited to the large bowel mucosa, thus complete large bowel resection was expected to be curative. Nonetheless, about 60% of patients who undergo total proctocolectomy with an ileal pouch reservoir develop pouchitis. Recently we performed mRNA profiling and detected an increase in Dual Oxidase 2 (DUOX2) expression in inflamed pouch biopsies as well as in CD patients. Duox2 mediates anti pathogen responses in intestinal epithelial cells by secreting reactive oxygen species (ROS) to the lumen, and its expression may be induced by microbiota.

Aims & Methods: We aimed to decipher the mechanism responsible for DUOX2 effects in the intestinal inflammation. Intestinal biopsies from normal controls, inflamed and non-inflamed UC, CD and pouch patients were collected. Disease activity was defined using clinical disease scores, as well as endoscopic and histologic assessment. DUOX2 mRNA and protein levels were assessed by RT-PCR and immunohistochemistry. DUOX2 intracellular localization as well as activity (extracellular ROS production) were assessed by flow cytometry and amplex red assay, respectively, in human intestinal epithelial cell lines (Caco2 and HT-29) in response to inflammatory cytokines (IL1b, TNFa, IFNg, IFNb) and fecal extracts obtained from IBD patients. Microbiota composition in patients with IBD as well as controls was assessed by 16S rRNA gene amplicon pyrosequencing.

Results: DUOX2 expression in the non inflamed colonic mucosa of IBD patients was increased (30 fold, p < 0.05). This was further augmented in the inflamed colon (≥ 150 fold, p < 0.001), both compared to normal controls. Similar results were obtained in biopsies generated from the ileum. Decrease in key microbial taxa was observed in fecal samples from patients with a normal pouch compared to normal controls (p < 0.004). Further decrease was noticed in fecal extracts from patients with pouchitis (p < 0.0001). DUOX2 expression significantly increased in response to inflammatory cytokines (≥300 fold increase, p < 0.001) and fecal extracts derived from patients with active IBD (≥10 fold increase, p < 0.001). ROS production reflecting Duox2 activity, increased in response to fecal extracts derived from patients with active IBD (3 fold, p < 0.001).

Conclusion: Mucosal DUOX2 expression is increased in IBD, and correlates with inflammation. DUOX2 expression in epithelial cells is increased in response to inflammatory stimuli and fecal extracts, specifically from patients with active IBD. ROS production is increased in response to fecal extracts but not to inflammatory cytokines alone. Thus DUOX2 increased expression and aberrant function may have a role in augmenting intestinal inflammation in IBD.

Disclosure of Interest: None declared

P0899 MAPPING BIOPSY OF ENTIRE SMALL INTESTINE REVEALED SPECIFIC GENE EXPRESSION IN CROHN’S DISEASE

K. Tsuchiya¹, R. Hayashi², S. Hibiya¹, K. Fukushima¹, N. Horita¹, T. Shirasaki¹, M. Watanabe¹

¹Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, ²Hiroshima University, Hiroshima, Japan

Introduction: The discovery of genetic variants in Crohn’s disease (CD) has helped us to understand the pathogenesis of CD. Notably, genetic variants of nucleotide-binding oligomerization domain containing 2(NOD2) and autophagy related 16-like 1 (ATG16L1) have indicated that mucosal barrier dysfunction is one of the most crucial pathogenesis in CD. However, the patients with CD in Asia including Japan and China did not have significant variants of these genes, suggesting that the other molecular mechanism of the pathogenesis might be involved in Asian patients differently from Caucasian patients.

Aims & Methods: In this study, we therefore aimed to elucidate the molecular mechanism of the pathogenesis in Japanese patients with CD, using mapping biopsy of entire small intestine collected by balloon-assisted enteroscopy.

We performed balloon-assisted enteroscopy to the patients with CD and healthy controls. Then we collected five biopsy specimens in equal interval positions through entire small intestine assisted by X-ray. Gene expression pattern in each region of entire small intestine was analyzed by using Self-Organizing Maps (SOM). Specific gene expression in CD was detected by the microarray analysis of 16 biopsy specimens of jejunum in 4 CD patients compared to 4 healthy controls.

Results: RNA was successfully generated from mapping biopsy specimens. SOM analysis compared CD with healthy control revealed that any inflammatory genes were not increased in jejunum of CD patients, suggesting that the pathogenesis at the pre-onset stage of CD might remain in jejunum. Microarray analysis in 16 jejunum biopsy specimens compared between 4 CD patients and 4 healthy controls showed statistically significant gene expression including 11 up regulated genes and 14 down regulated genes in CD patients.

Conclusion: The analysis of comprehensive gene expression using mapping biopsy is useful for understanding the condition in human entire small intestine. Moreover, it might be useful to elucidate the pathogenesis of CD.

Disclosure of Interest: None declared

P0900 CORRELATION OF HISTOLOGICAL ACTIVITY AND BASAL PLASMACYTOSIS WITH MUCOSAL HEALING IN ULCERATIVE COLITIS PATIENTS

K. Farkas¹, Z. Reisz², A. Sejben², L. Tiszlavicz², M. Szűcs³, Z. Szepes¹, F. Nagy¹, M. Rutka¹, A. Bálint¹, R. Bor¹, Á. Milassin¹, T. Molnár¹

¹1st Department of Medicine, ²Department of Pathology, ³Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary

Contact E-mail Address: farkas.klaudia@gmail.com

Introduction: Microscopic activity in ulcerative colitis (UC) patients with endoscopic remission is becoming more and more important in the prediction of relapse. The presence of basal plasmacytosis and the increased number of eosinophils and neutrophils in the lamina propria have been supposed to predict clinical relapse in UC patients with complete mucosal healing.

Aims & Methods: The aim of this study was to examine the correlation between the microscopic activity and the disease outcome in patients with endoscopically inactive UC. Sixty-nine UC patients (mean age at diagnosis was 31.4 years, male/female ratio: 27/42) with endoscopic remission (eMayo 0 and 1) and at least 12-month follow-up between 2008 and 2013 were enrolled in this prospective observational study. An expert pathologist evaluated all colonic biopsies for histologic activity (Geboes score) and the presence of basal plasmacytosis. C-reactive protein (CRP), partial Mayo scores and the used medications were documented at the time of the endoscopy, and the follow-up appointments: at months 6, 12 and 24 and at the last visit. Disease relapse was defined as a partial Mayo score ≥3.

Results: Histology revealed focal or diffuse basal plasmacytosis and microscopic inflammatory activity with a Geboes score ≥3.1 in 81.2% and 37.7% of patients with mucosal healing. At 6, 12 and 24 months and at the follow up visit, clinical relapsed occurred in 19%, in 14.5%, in 13%, and in 16% of the patients. The mean time of follow-up was 3 years. Neither of the presence of basal plasmacytosis, nor Geboes score ≥3.1 was predictive of disease relapse at 6, 12, 24 months and at follow-up. No difference was observed if the data were analyzed separately in subgroups of eMayo score of 0 or 1.

Conclusion: Our results did not confirm the previous hypothesis that the presence of basal plasmacytosis and microscopic inflammation predicts UC clinical relapse in patients with mucosal healing.

Disclosure of Interest: None declared

P0901 CRITICAL ROLE OF THE IL-33/ST2 AXIS IN COLITIS-ASSOCIATED COLORECTAL CANCER

L. R. Lopetuso¹², C. De Salvo¹, L. Di Martino³, W. Goodman¹, F. Scaldaferri², A. Gasbarrini², T. T. Pizarro¹

¹Pathology, Case Western Reserve University - School of Medicine, Cleveland, United States, ²Internal Medicine, Gastroenterology Division, Catholic University of Sacred Heart of Rome, Rome, Italy, ³Digestive Health Research Center, Case Western Reserve University, Cleveland, United States

Introduction: It is now well-established that IL-33 and its receptor, ST2, are important factors in the pathogenesis of IBD. Emerging evidence also suggests its critical role in epithelial proliferation and potential contribution to inflammation-driven tumorigenesis that can lead to colorectal cancer (CRC). The aim of our study was to characterize the precise contribution of IL-33/ST2 axis in the azoxymethane (AOM)/dextran sodium sulfate (DSS) model of colitis-associated CRC.

Aims & Methods: C57/BL6 wild-type (WT), IL-33 KO and ST2 KO mice were given a single dose of AOM (7.4 mg/kg) followed by two cycles of 3% DSS for 7d in drinking water. Body weight, occult blood test, and stool consistency were measured daily to calculate the Disease Activity Index (DAI), and endoscopic and histological evaluation of colons were performed using established scoring systems. Aged-matched WT mice, injected with vehicle and given regular drinking water were used as controls (CT). At 8 wks post AOM injection mice were sacrificed. IHC, immunofluorescence (IF) and qPCR were done on full-thickness colons for IL-33 and ST2 localization and identification, and mRNA expression, respectively. FACS analysis was performed on resected, isolated polyps in order to functionally characterize ST2+ cells.

Results: IL-33, ST2L, and sST2 mRNA transcripts were dramatically elevated in WT vs. CT mice. IHC of treated WT mice revealed localization of IL-33 to the colonic epithelium and to cells within the LP morphologically consistent with tissue macrophages. ST2 staining was localized to the intestinal epithelium in tissues immediately adjacent to tumors, while within the tumors themselves, ST2+ cells displayed a spindle/fibroblast-like morphology with a unique distribution throughout the polyps. Little to no staining for both IL-33 and ST2 was present in CT. Using IF, ST2 co-localized with αSMA in polyps; however, ST2 staining was not exclusive for αSMA+ cells. FACS analysis showed a distinct population of CD45+ hematopoietic cells consisting of CD3/CD8+ cytotoxic T cells (CTLs), CD19+ B-lymphocytes, and CD11b + CD11c- and CD11b + CD11c+ myeloid cells. ST2 was mainly expressed by CTLs, CD11b + CD11c- and CD11b + CD11c+ myeloid cells. Non-hematopoietic cells (CD45-) also expressed ST2. DSS challenge in WT mice resulted in increased body weight loss and DAI vs. IL-33 KO and ST2 KO mice. At 5 weeks post AOM injection, experimental mice underwent survival colonoscopy. WT had already developed protruding lesions with abnormal vascular patterns, suggesting pre-tumorous lesions, while IL-33 KO and ST2 KO mice showed the absence of pre-tumorous lesions with a more impressive mucosal inflammation, likely due to reduced epithelial proliferation and repair caused by the absence of IL-33 signaling. At sacrifice, increased number and size of polyps were observed in WT vs. IL-33KO and ST2KO mice.

Conclusion: Our results suggest that activation of the IL-33/ST2 axis sustains tumorigenesis in the murine model of colitis-associated CRC. Further studies are underway to determine mechanisms of action that support these findings.

Disclosure of Interest: None declared

P0902 PSC - IBD IS ASSOCIATED WITH DIFFERENT MICROBIOTA COMPOSITION AS COMPARED TO UC

L. Bajer¹, J. Mrazek², M. Kverka³, J. Dvorak³, M. Kostovcik³, H. Tlaskalova - Hogenova³, J. Brezina¹, J. Spicak¹, P. Drastich¹

¹Hepatogastroenterology, Institute for Clinical and Experimental Medicine, ²Institute of Animal Physiology and Genetics ASCR, ³Institute of Microbiology ASCR, Prague, Czech Republic

Contact E-mail Address: lukasbajer1@gmail.com

Introduction: Primary sclerosing cholangitis (PSC) is a progressive disease of the biliary tree characterised by inflammation, fibrosis and stenoses. Inflammatory bowel disease (IBD) in patients with primary sclerosing cholangitis (PSC – IBD) is considered to be a distinct phenotype of IBD with a multi – factorial origin where microbiota most likely have a substantial role. In our pilot study, our aim was to compare the microbiota composition in PSC and/or IBD groups with ulcerative colitis (UC) and healthy controls.

Aims & Methods: Total number of 15 individuals was used in presented study: 4 control healthy samples, 4 UC patients, 4 PSC-IBD patients and 3 PSC (without IBD). Fecal microbiota composition was assesed by sequencing of variable V4 and V5 region of 16S rRNA gene on Personal Genome Machine platform (Fisher Scientific). Library preparation, template preparation and template sequencing was performed according to manufacturer’s protocols. Obtained data were filtered by quality and length and processed for alpha and beta diversity analyses using QIIME software package.

Results: Following significant changes in bacterial numbers were observed among tested groups: PSC versus PSC-IBD: Higher Bifidobacterium sp. (18 vs 2.71 %), Lachnospira (4.58 vs 0.68 %) and Dorea sp (5.7 vs 1.55 %) and lower Enterococcus sp. (0 vs 9.14 %), Faecallibacterium sp. (1.31 vs 4.12 %) and Prevotella/Paraprevotella sp. (0 vs 9.71 %) numbers. PSC-IBD versus UC: Higher Bacteroides sp. (17.13 vs. 4.86 %), Enterococcus sp. (9.14 vs 0 %) and Prevotella/Paraprevotella sp. (9.71 vs 2.13 %) and lower Bifidobacterium sp (2.71 vs 12.95 %) and Faecallibacterium sp. (4.12 vs 16.4 %) numbers. The clustering of samples according to the type is stronger with the unweighted UniFrac metric than with the weighted metric, suggesting that differences in community membership (rather than community structure) discriminate better among groups.

Conclusion: Members of genus Faecallibacterium and Prevotella showed highest variations with regards to PSC /PSC-IBD/UC groups comparison. Control samples showed higher species richness than patients’ samples. Our data suggest that microbiota composition differs among patients with PSC (without IBD), PSC – IBD and UC. Presented data should be considered as preliminary, as more samples are needed for statistical analyses to support detected observations.

Disclosure of Interest: None declared

P0903 EVP-6124, A SELECTIVE A7 NICOTINIC ACETYLCHOLINE RECEPTOR PARTIAL AGONIST, IMPROVES EXPERIMENTAL COLITIS IN MICE AND REDUCES IMMUNE CELL INFILTRATION IN THE COLON

M. Salaga¹, L. Blomster², A. Piechota-Polanczyk¹, M. Zielinska¹, D. Jacenik³, A. Cygankiewicz³, W. Krajewska³, J. Mikkelsen², J. Fichna¹

¹Deartment of Biochemistry, Medical University of Lodz, Lodz, Poland, ²Neurobiology Research Unit, University Hospital Rigshospitalet, Copenhagen, Denmark, ³Department of Cytobiochemistry, University of Lodz, Lodz, Poland

Contact E-mail Address: salaga.maciej@gmail.com

Introduction: The parasympathetic nervous system and vagal nerve in particular are responsible for anti-inflammatory signaling from the central nervous system (CNS) to the periphery. α7 homopentamer nicotinic acetylocholine receptors (nAChRs) have been implicated in the transduction of these signals to the gastrointestinal (GI) tract, but the underlying mechanisms are still unclear.

Aims & Methods: The aim of this study was to investigate the anti-inflammatory effect of the novel, selective α7 nAChR partial agonist, EVP 6124 in mouse models of experimental colitis, and to determine the mechanism underlying its activity. To assess the anti-inflammatory activity of EVP 6124, we used trinitrobenezenesulfonic acid (TNBS)- and dextran sulfate sodium (DSS)-induced models of colitis. Macroscopic score, ulcer score, colon length and thickness, as well as myeloperoxidase (MPO) activity were recorded. To confirm the selectivity of the test compound, we used α7 nAChRs antagonist methyllycaconitine (MLA). Moreover, we used hexamethonium (HEX) to investigate whether centrally- or peripherally-located nAChRs are involved in the effects of EVP6124. Quantitative immunohistochemistry (IHC) was used to measure the infiltration of macrophages, neutrophils, T cells and B cells in the colon. Furthermore, we employed flow cytometry to determine the effect of EVP6124 on frequencies of FoxP3⁺and IL-17A⁺ T cells in the mouse colon. Additionally, we assessed the effect of EVP6124 on the viability of mouse spleen-derived monocytes. Changes in α7 nAChR mRNA expression in the colonic tissue during colitis and after treatment with EVP 6124 were quantified by real time RT PCR.

Results: The intraperitoneal (i.p.) administration of EVP6124 (3 mg/kg, twice daily) attenuated TNBS- and DSS-induced colitis in mice, as indicated by significantly reduced macroscopic parameters and MPO activity; this effect was blocked by the i.p. administration of MLA (3 mg/kg, twice daily). Treatment with EVP6124 significantly reduced the infiltration of macrophages, neutrophils and B cells in the colon of TNBS-treated animals, as indicated by the quantitative IHC. In the TNBS model the frequency of pro-inflammatory FoxP3⁺IL-17A⁺T cells was significantly reduced in the colon of EVP6124-treated animals. In the DSS model treatment with EVP6124 increased the frequency of immunosuppressive FoxP3⁺T cells and reduced pro-inflammatory IL-17A⁺T cells. Moreover, EVP6124 reduced the viability of mouse spleen-derived monocytes in a dose-dependent manner. α7 nAChR mRNA was significantly increased in the colitic animals vs. healthy controls.

Conclusion: We show that stimulation of α7 nAChR with a partial agonist EVP6124 alleviates colitis via alteration of the number and/or activation status of the immune cells in the gut. Therefore, we highlight the potential of EVP6124 to become an anti-IBD drug, especially given that initial studies with EVP6124 in healthy volunteers showed that this compound is safe and well-tolerable.

Disclosure of Interest: None declared

P0904 CHARACTERIZATION OF BACTEROIDETES ASSOCIATED WITH INTESTINAL MICROBIOTA IN PATIENTS WITH CROHN’S DISEASE AND ANALYSIS OF ITS EFFECT IN THE INDUCTION OF INTESTINAL INFLAMMATION IN MICE

M. Barreiro-De Acosta¹², R. Sueiro³, A. P. De Felipe³, L. Uribarri-González¹², R. Ferreiro-Iglesias¹², J. M. Leiro³, J. E. Domínguez-Munoz¹²

¹University Hospital of Santiago de Compostela, ²Foundation for Research in Digestive Diseases, ³Institute of Food Research and Analysis, University of Santiago de Compostela, Santiago de Compostela, Spain

Contact E-mail Address: info@fienad.org

Introduction: The pathogenesis of inflammatory bowel disease (IBD) involves an imbalance of the gut microbiota generating an inappropriate activation of the mucosal immune system in genetically predisposed individuals. The human commensal microbiota contains a large number of Bacteroidetes species that may cause inflammation in animal models.

Aims & Methods: The aim of this study was to detect and evaluate the influence of a major type of intestinal commensal bacteria belonging specifically to the order Bacteroidales on the activity of Crohn disease (CD). In addition, the effect of these bacteria isolated from CD patients on gut inflammation was evaluated in mice after transplantation.

Methods: We performed a case control study on the intestinal bacteria of the phylum Bacteroidetes from faeces of CD and healthy controls (HC) using a polymerase chain reaction (PCR) designed to detect human-specific genetic markers targeting Bacteroidetes-like 16S rRNA genes in fecal DNA samples. The PCR products from the 16S rRNA genes were digested with HinfI, PciI, DpnII and AciI enzymes and restriction fragment length polymorphism (RFLP) were determined. RFLP and sequencing analysis indicated that a total of 6 bacterial genotypes do exist: N1, C1, C2, C3, C4 and C5 (of which N1 genotype is probably a strain of Bacteroides dorei and C1, and maybe C2, strains of B. vulgatus). The relationship between CD activity (CDAI > 150) and microbiota was also evaluated. Microbiota from CD patients was transplanted into mice gut to evaluate their ability to induce inflammation. Results are shown in percentages.

Results: 11 CD patients (8 with active CD -aCD- (CDAI > 150), and 3 with inactive CD –iCD-), and 11 HC were included. The predominant Bacteroidetes genotype in feces from HC and iCD was N1 (in 100% of samples), whereas this genotype was found in only 28% of patients with aCD. 18% aCD patients showed the C1 genotype, 9% the C1 and C3 genotypes together, 18% the C4 genotype, and 27% the C1 and C4 genotypes together. The transplant of bacteria from CD patients to mice led to large bowel inflammation, and the stool of the transplanted mice consisted in 30% C4 genotype and had a high level of Bacteroidetes cluster in comparison with the mice transplanted with bacteria from HC.

Conclusion: The fecal microbiota of CD patients is different from those of HC in that they present a wide variety of Bacteroidetes cluster genotypes. The C4 genotype by itself, or together with the C1 genotype, seems to be intimately related to the activity of the disease. These results were also confirmed in transplanted mice.

Disclosure of Interest: None declared

P0905 INTESTINAL ORGANOIDS DERIVED FROM INFLAMMATORY BOWEL DISEASE PATIENTS SHOW UNALTERED TRANSCRIPTIONAL PROFILES WHEN COMPARED TO HEALTHY CONTROL ORGANOIDS

M. Noben¹², N. Hendriks¹², G. Van Assche¹, S. Vermeire¹, C. Verfaillie², M. Ferrante¹

¹Translational Research in GastroIntestinal Disorders (Targid), ²Department of Development and Regeneration, KU Leuven, Leuven, Belgium

Contact E-mail Address: Manuel.Noben@med.kuleuven.be

Introduction: Various mechanisms contribute to the pathogenesis of inflammatory bowel diseases (IBD), including defects in epithelial barrier function, Paneth cell or goblet cell dysfunction, and a microbial dysbiosis. The epithelium is constantly renewed by intestinal stem cells (ISCs) located at the bottom of the crypts. The ex vivo ISC-containing organoids, have demonstrated to be a suitable model to investigate cancer and cystic fibrosis.

Aims & Methods: Given the reported defects in epithelial barrier and Paneth cell function, we evaluated if the organoid forming capacity of colonic crypts, as well as organoid transcriptional profiles, from IBD patients differ from that of healthy controls (HC).

Colonic mucosal biopsies from 9 HC, 14 ulcerative colitis (UC) patients, and 12 Crohn’s disease (CD) patients were used to culture organoids as previously described.^{1, 2} After the second passage, organoids were differentiated for 4 days by withdrawal of Wnt3a, nicotinamide and p38-inhibitor from the medium. RNA and histology samples were then processed and analysed using qPCR (SYBR Green qPCR SuperMix-UDG, Invitrogen) and immunohistochemistry for ISCs and differentiated cell types (goblet cells, entero-endocrine cells, Paneth cells, enterocytes), as well as proliferation and apoptosis (Ki-67 and cleaved caspase 3 staining).

Results: There was no difference in initial organoid forming capacity between controls and IBD patients (HC 85.9%; UC 78.6%; CD 83.1%, HC vs. UC P=0.2794, HC vs. CD P=0.2204, and UC vs. CD 0.8370). Additionally, no intrinsic differences in expression of the ISC-marker Lgr5 or differentiated cell types were detected. However, in the undifferentiated organoids there was a significant increase in chromogranin A (CHGA) expression in CD patient-derived organoids (P=0.0384, table 1). In differentiated organoids there was a significantly decreased expression of proliferating cell nuclear agent (PCNA) in organoids from CD patients when compared to HC organoids (P=0.0099). The biological implications of these findings are currently being evaluated by immune-stainings of organoid sections.

Table 1.

Comparison of deltaCt values per group. UC = ulcerative colitis (n=7), CD = Crohn’s disease (n=8), HC = healthy control (n=9).

Comparison colonic organoids	Gene	P-value
UC vs HC undifferentiated	Chromogranin A	0.8125
CD vs HC undifferentiated	Chromogranin A	0.0384
UC vs CD undifferentiated	Chromogranin A	0.1137
UC vs HC differentiated	PCNA	0.0541
CD vs HC differentiated	PCNA	0.0099
UC vs CD differentiated	PCNA	0.4179
UC vs HC undifferentiated	Mucin2	0.0939

Conclusion: Our data shows that intestinal crypts isolated from IBD patients form organoids as efficient as crypts from healthy controls. Gene expression of markers of stemness and differentiation showed only subtle differences, and the biological implications remain to be clarified via immunohistochemistry.

Disclosure of Interest: M. Noben: None declared, N. Hendriks: None declared, G. Van Assche Financial support for research: MSD, Abbvie, Lecture fee(s): MSD, Abbvie, Takeda, Ferring, Consultancy: MSD, Abbvie, Takeda, Ferring, Genetech/Roche, Pfizer, S. Vermeire Financial support for research: MSD, Abbvie, Lecture fee(s): MSD, Abbvie, Takeda, Falk, Tillotts, Consultancy: MSD, Abbvie, Takeda, Falk, Ferring, Shire, Galapagos, Hospira, Mundipharma, Genetech/Roch, Pfizer, Celgene, C. Verfaillie: None declared, M. Ferrante Financial support for research: Takeda, Lecture fee(s): Abbvie, Janssen, MSD, Chiesi, Tillots, Zeira, Consultancy: Abbvie, Janssen, MSD, Boehringer-Ingelheim, Ferring

P0906 DIFFRENT CORRELATION OF CD99 AND CYCLOPHILIN A IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES

M. Włodarczyk¹², A. Sobolewska¹², K. Stec-Michalska¹, M. Cichalewska³, J.-P. Timmermans⁴, M. Mycko³, J. Fichna², M. Wiśniewska-Jarosińska¹, A. Piechota-Polańczyk²

¹Department of Gastroenterology, ²Department of Biochemistry, ³Laboratory of Neuroimmunology, Department of Neurology, Medical Univeristy of Lodz, Łódź, Poland, ⁴Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium

Contact E-mail Address: dr.mwlodarczyk@gmail.com

Introduction: Inflammatory bowel diseases (IBD) are characterized by crypt infiltration with neutrophils, which can be stimulated by externalization of an adhesion molecule CD99. Neutrophil infiltration is associated with upregulation of cyclophilin A (CyPA). However, studies on CD99 and CyPA in IBD patients have not been performed yet.

Aims & Methods: The aim of the study was to determine the CD99 gene and protein expression and extra- and intracellular concentration of CyPA in ulcerative colitis (UC) and Crohn’s disease (CD) patients in comparison to healthy subjects. Patients with Crohn’s disease (CD) and ulcerative colitis (UC) as well as healthy controls were enrolled in our study. All participating subjects were matched by age and gender. The samples comprised serum and colonoscopy biopsies from non-inflamed and inflamed (in UC or CD) colon areas. The CD99 mRNA was analyzed by RT-PCR, and CD99 and CyPA protein levels by immunoenzymatic methods (ELISA and Western blot).

Results: In UC patients, a tendency towards lower CD99 protein (p=0.084), but not mRNA was observed compared with control. There was no relationship between CD and control in CD99 mRNA and protein level (p=0.735 and p=0.446, respectively). The UC patients had significantly lower CD99 mRNA in non-inflamed tissue and higher in inflamed colon areas compared with CD (p=0.035 and p=0.021, respectively). The extracellular CyPA level was 4.6- and 2.8-times higher in UC and CD than in control (p=0.017 and p=0.137, respectively). Reversed correlations were found between CyPA and CD99 in inflamed tissues of UC and CD patients.

Abstract number: P0906 Table.

Correlations between CD99 and CyPA in non-inflamed and inflamed colon areas in UC and CD patients.

	UC		CD
	r2		r2
mRNA level	Protein level	mRNA level	Protein level
CyPA [ng/ml] in plasma vs. CD99 in non-inflamed colon areas	+0.770	+0.530	-0.651	-0.274
CyPA [ng/ml] in plasma vs. CD99 in inflamed colon areas	-0.535	+0.090	-0.344	-0.478
CyPA [ng/ml] in non-inflamed vs. CD99 in non-inflamed colon areas	-0.580	-0.086	-0.357	-0.756
CyPA [ng/ml] in inflamed vs. CD99 in inflamed colon areas	+0.796	+0.488	+0.436	-0.333

Conclusion: Our study indicated that patients with UC had increased CD99 and CyPA both in plasma and tissue. Moreover, CD99 gene expression correlated inversely with intracellular CyPA level in inflamed and non-inflamed colon tissue in UC, but not CD. We suggest that there may be a link between CD99 and CyPA in IBD etiology. It is likely that CD99-CyPA interaction influences the inflammatory process in colitis, as in our study both CD99 and CyPA were increased in inflamed colon areas from UC patients. However, further studies are necessary to confirm those observations and to describe how, if at all, CyPA releasing influences CD99 signaling in IBD.

Disclosure of Interest: None declared

P0907 IMMUNE-SURVEILLANCE FAILURE PREDICTS DYSPLASIA PERSISTENCE IN ULCERATIVE COLITIS

M. Scarpa¹, R. D'Incà², A. Kotsafti¹, M. Scarpa¹, M. Fassan³, N. Bortoli², P. Brun⁴, M. Bortolami², I. Angriman², M. Rugge³, G. C. Sturniolo², I. Castagliuolo⁴, C. Castoro¹

¹Oncological Surgery Unit, Veneto Institute of Oncology (IOV-IRCCS), ²Dept of surgical, Gastroenterological and Oncological Sciences, ³Dept of Medicine, ⁴Dept of Molecular Medicine, University of Padova, Padova, Italy

Contact E-mail Address: marcoscarpa73@yahoo.it

Introduction: In patients with ulcerative colitis (UC) chronic inflammation leads to dysplasia development in 10-20% of cases. Our previous studies demostrated that immunesurveillance mechanisms mediated by CD80-CD28 signalling may lead to dysplasia regression [1]. The persistence of low-grade dysplasia (LGD) in UC in two consecutive observations may be an indication for restorative proctocolectomy.

Aims & Methods: Our hypothesis is that a failure of immune surveillance mechanism may play a role in dysplasia persistence and we aimed to identify possible immunological markers of LGD persistence in colonic mucosa not affected by dysplasia.

We prospectively enrolled 95 UC patients who underwent screening colonoscopy who had biopsies taken from their sigmoid colon. Forty of them had at least a second colonoscopy and 6 patients had dysplasia in both exams suggesting a persistence of LGD in their colon. Real-time RT-PCR for TLR4, CD4, CD38, CD69, CD80 and CD8beta mRNA expression was performed. Flow cytofluorimetry for CD8+ lymphocytes expressing CD28 or CD38 and for epithelial cells expressing CD80 or HLA ABC were performed. Non parametric statistics, ROC curves analysis and logistic multiple regression analysis were used.

Results: We observed a lower CD38 and CD8beta mRNA expression in the healthy colonic mucosa of patients with LGD persistence (p=0.027 and p=0.005, respectively) as well as a lower level of activated cytotoxic T-cells (CD8 + CD38+) (p=0.042). ROC curve analysis showed that lower level of activated cytotoxic T-cells (CD8 + CD38+) as well as low CD4, CD38, and CD8beta mRNA expression predicted with adequate accuracy the LGD persistence at a second colonoscopy. In particular, CD8beta mRNA levels showed the best accuracy (AUC=0.87 [95%CI=0.70-0.96], p < 0.001). At multivariate survival analysis in a model including CD8beta mRNA levels, disease duration and inflammatory grade showed that only CD8beta mRNA levels were independent predictor of dysplasia at follow up (OR=0.033 [95%CI=0.002-0.433], p=0.01).

Conclusion: These data suggest a failure in immunesurveillance mechanisms in the colonic mucosa of UC patients who do not manage to clear dysplasia. Thus, low level of CD8beta mRNA expression in not dysplastic colonic mucosa might be used in the decision making of UC management as a predictor of persistence of dysplasia.

Disclosure of Interest: None declared

P0908 COMPARATIVE GENOMICS BETWEEN AIEC/NON-AIEC STRAIN PAIRS FOR THE DETECTION OF GENETIC ELEMENTS IMPLICATED IN THE ADHERENT-INVASIVE E. COLI PHENOTYPE

M. Martinez-Medina¹, M. Lopez-Siles¹, M. Ferrer-Guixeras¹, C. Camprubí-Font¹, C. Abellà-Ametller¹, J. Garcia-Gil¹

¹Biology, University of Girona, Girona, Spain

Contact E-mail Address: marga.martinez@udg.edu

Introduction: Adherent-invasive Escherichia coli (AIEC) have been implicated in the aetiology of Crohn’s disease (CD) but the molecular basis of its pathogenicity is still not well resolved. Obtaining molecular tools specific for AIEC is of great relevance as the current available techniques to identify the pathotype are based exclusively in phenotypic screening of cultured bacteria, which is highly time-consuming.

Aims & Methods: Our aim was to identify genetic elements that could be involved in the AIEC phenotype in order to gain insight into the mechanisms of pathogenicity of the pathotype and to find out molecular targets for its identification.

The genome of three pairs of E. coli strains with identical pulsed field gel electrophoresis fingerprints and virulence gene profiles but differing in the AIEC phenotype (AIEC and Non-AIEC respectively) was sequenced de novo combining HiSeq and PacBio using paired-end libraries. The three pairs covered different phylogenetic groups and, with the exception of one strain, each pair shared the same serogroup. Genome assembly, functional annotation and comparative genomics between pairs was performed to obtain genetic differences between AIEC and non-AIEC strains. Additionally, single nucleotide polymorphisms (SNPs) were searched by comparing the Non-AIEC strains with both their AIEC pair and a reference AIEC of the same phylogroup. We used the genome of AIEC LF82 for the O6:H1-B2 pair, the AIEC 576-1 for the ONT:HNT/O46:H32-D pair, and the AIEC 541-1for the O22:H7-B1 pair.

Results: Quality analysis indicated the reads achieved quality scores above Q30, thus the inferred base call accuracy was above 99.9%. Genome length of AIEC strains O6:H1-B2, ONT:HNT-D and O22:H7-B1 was 5.16, 4.86 and 4.79 MB respectively. Their non-AIEC counterpart presented +30,515bp, +12,270bp and –54,427bp respectively. After a selection of confirmed differences in silico we have identified 11, 15 and 28 genetic differences respectively, including SNPs, insertions and deletions. Of them, 29 were found in genes that were in commonly shared in all the strains but the mutations were not AIEC-specific. New SNPs calling comparing the three pairs with reference AIEC strains of the same phylogroup allowed the identification of 185, 182 and 354 SNPs commonly shared by AIEC strains and not found in the Non-AIEC pair respectively, which lead to missense variants. To the moment, no AIEC-specific sequence widely distributed in all AIEC was found among the selected genes. Selected genes included adhesins, transporters, enzymes, toxins and transcriptional regulators that could be involved in the pathogenicity of the strains.

Conclusion: New genes that could be involved in the pathogenicity of AIEC have been identified. In vitro studies are needed to demonstrate their role. Additional coding and non-coding sequences must be analyzed to find out putative genetic markers for AIEC. Identifying the genetic elements associated with the AIEC phenotype may help to better understand the mechanisms of pathogenicity of the pathotype and also could imply a significant advance in the detection of new therapeutic targets for CD.

Disclosure of Interest: None declared

P0909 EVALUATION OF MALE SEXUAL FUNCTION IN MEN WITH INFLAMMATORY BOWEL DISEASE

M. P. Valer¹, D. Santos², A. Algaba¹, P. Lopez³, M. Chaparro⁴, E. Quintanilla⁵, M. Hernandez¹, B. Piqueras¹, G. De la Poza¹, F. Bermejo¹

¹Gastroenterology, Hospital de Fuenlabrada, ²Urology, Hospital Clinico San Carlos, ³Gastroenterology, Hospital de Alcorcon, ⁴Gastroenterology, Hospital de la Princesa, Madrid, ⁵Gastroenterology, Hospital Severo Ochoa, Leganes, Spain

Contact E-mail Address: pazvaler@yahoo.es

Introduction: The inflammatory bowel disease (IBD) per se and the therapies used for the treatment of this disease could have effect on the sex and sexuality of male patients. Also, as medical therapy in IBD has advanced, more patients are healthy enough to consider conception. The aim of the present study was to evaluate the impact of IBD on the male sexual function and satisfaction.

Aims & Methods: A multicentre, transversal study was performed in male subjects with IBD and controls (CTR) between April 2010 and March 2014. All the participants had between 18 and 45 years old and were assessed by a medical history and physical examination before inclusion. The presence of varicocele, altered FSH, LH, prolactine or testosterone levels or having any pathology related to subfertility was considered as exclusion criteria. To evaluate the male sexual function The International Index Erectile Function questionnaire (IIEF-15) validated in Spanish language were used. The global score and the five items about sexual function (erectile function, orgasmic function, sexual desire, intercourse satisfaction and overall sastisfaction) were calculated from each patient. To investigate if anti-TNF therapy affected male sexual function, the IIEF-15 scores were calculated in CD patients with biological therapy and compared with patients without this therapy.

Results: Fifty-two patients with IBD (30 CD, 22 ulcerative colitis (UC)) and 22 CTR were included. When the 3 groups (CD, UC and CTRL) were compared, no significant statistical differences were found respect to global score (IEEF15 CD 66.1 ± 7.7; UC 62.5 ± 12.9; CTRL 68.3 ± 8.7; p > 0.05), erectile function (CD 26.1 ± 7.5; UC 25.2 ± 7.6, CTRL 28.6 ± 3.6, p > 0.05), sexual satisfaction (CD 11.3 ± 4.6, UC 10.6 ± 4.4, CTRL 13.1 ± 3.5; p=>0.05), orgasmic function (CD 9.2 ± 2.1; UC 9.6 ± 0.6; CTRL 10 ± 0. p > 0.05) or sexual desire (CD 7.1 ±2.0, UC 7.2 ± 2.2, CTRL 7.5 ± 1.8, p > 0.05). However, patients with UC had worse global satisfaction in IEF15 than CD patients (CD 8.5 ± 1.2; UC 7.2 ± 2.4; CTRL 9.1 ± 1.1 p=0.03). The IIEF-15 score was no difference in patients with CD with (n=10) and without anti-TNF (n=20) therapy (p < 0.05).

Conclusion: The male sexual function based on IIEF-15 questionnaire is not affected by IBD or anti-TNF drugs. Nevertheless, patients with UC have lower sexual satisfaction than patients with CD or controls.

Disclosure of Interest: M. P. Valer Financial support for research: GETECCU GRANT. FROM THE THEORY TO THE PRACTICE., D. Santos: None declared, A. Algaba Financial support for research: MERCK GRANT, P. Lopez: None declared, M. Chaparro: None declared, E. Quintanilla: None declared, M. Hernandez: None declared, B. Piqueras: None declared, G. De la Poza: None declared, F. Bermejo: None declared

P0910 AN IBD-ASSOCIATED VARIANT IN PTPN22 PROTECTS FROM DISEASE ONSET IN MOUSE MODELS OF COLITIS

M. R. Spalinger¹, S. H. Kasper¹, C. Gottier¹, S. Lang¹, G. Rogler¹², M. Scharl¹²

¹Division of Gastroenterology and Hepatology, University Hospital Zürich, ²Zurich Center for Integrative Human Physiology, University of Zürich, Zürich, Switzerland

Contact E-mail Address: Marianne.Spalinger@usz.ch

Introduction: Single nucleotide polymorphisms (SNP) in the gene locus encoding protein tyrosine phosphatase non-receptor type 22 (PTPN22) have been associated with inflammatory disorders, including IBD. Presence of the SNP rs2476601 results in a gain-of-function PTPN22 protein product and is associated with increased risk to develop autoimmune disorders, such as type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus, but reduces the risk for Crohn’s disease (CD) onset. We have previously shown that protein and mRNA levels of PTPN22 are reduced in intestinal biopsies from CD patients, and that loss of PTPN22 results in enhanced inflammatory cytokine secretion from mononuclear cells treated with interferon-gamma or the bacterial product muramyl dipeptide. In this study, we now addressed how presence of the gain-of-function variant in PTPN22 influences the susceptibility to intestinal inflammation in mouse models of colitis.

Aims & Methods: Colitis was induced in 10-12 week old female mice by administration of 2% DSS for 7 days (acute DSS colitis), administration of four cycles of DSS (1.5% DSS for 7 days, followed by 10 days normal drinking water each; chronic DSS colitis), or by transferring naïve T cells into RAG2-/- recipients. Wild-type (WT), PTPN22 deficient (PTPN22-/-), or mice expressing the IBD associated gain-of-function variant in PTPN22 (PTPN22-619W mice) were used for the study.

Results: While PTPN22-/- mice suffered from aggravated acute DSS colitis as determined by pronounced weight loss, increased endoscopic and histologic colitis scores (p < 0.05 each), PTPN22-619W mice reacted only weak to the DSS treatment when compared to WT littermates (p < 0.05 for weigh development, p < 0.01 for other parameters). In chronic DSS colitis however, PTPN22-/- mice suffered from a milder disease course (characterized by reduced weight loss [p < 0.05], decreased histological severity [p < 0.05]) from the third cycle on, while PTPN22-619W mice tended to show a more pronounced disease course from the third DSS cycle on. In the T cell transfer model, PTPN22-/- T cells induced a more severe colitis as observed by an enhanced histological pathology (p < 0.05), while weight loss was not affected when compared to mice receiving WT T cells. In contrast, mice transfected with PTPN22-619W T cells were protected from disease development in the first four weeks, and later on developed a mild disease course (moderate weight loss [p < 0.01], reduced shortening of the colon [p < 0.05], mild histological disease scores [p < 0.05]) when compared to mice receiving WT T cells.

Conclusion: During acute inflammation, loss of PTPN22 results in enhanced colitis severity, while presence of the gain-of-function PTPN22 variant protects from colitis development. In chronic disease, compensatory mechanisms are able to reverse the increased disease susceptibility in PTPN22-/- mice, finally resulting in reduced disease severity, while presence of the gain-of-function variant is no longer able to protect from colitis. We here describe for the first time how the IBD-associated variant in PTPN22 affects colitis development what helps to explain why this variant is associated with a reduced risk for CD onset.

Disclosure of Interest: None declared

P0911 ENTERIC GLIAL ALTERATIONS IN INFLAMMATORY BOWEL DISEASE

M. Freyssinet¹, T. Clairembault², S. Coquenlorge², J. Jaulin², C. Trang¹, E. Coron¹, S. Bruley des Varannes¹, M. Neunlist², M. Derkinderen², A. Bourreille¹

¹Institut des Maladies de L'appareil Digestif, Imad, Chu Nantes, ²U913, Inserm, Nantes, France

Introduction: Enteric glial cells are the most abundant cells of the enteric nervous system. In inflamatory bowel disease (IBD) patients, enteric glial cells (EGC) present some differences in the expression level of glial markers. Whether these changes are determined by the pathological environment or represent a constitutive feature of pathological EGC is unknown. The purpose of our study is (i) to determine ex vivo, the expression of glial markers in colonic biopsies from patients who have a Crohn's disease (CD), an ulcerative colitis (UC) and from control patients (CONT); (ii) to determine if the stimulation of EGC from rats in a primary culture by an inflamed environment could reproduce glial changes observed on human biopsies; (iii) try to reproduce glial changes observed in biopsies by the treatment of EGC from control patient in a primary culture, with supernatant from biopsies previously analyzed.

Aims & Methods: Biopsies of IBD patients (18 CD, 9 UC and 15 CONT) were performed by endoscopic procedures in inflamed area (I) and in non inflamed area (NI) for each patient. Culture of rat EGC were subjected to chronic inflammatory stress represented by TNFα and interleukin-1β (TI; 1ng/ml) or lipopolysacharide (LPS; 0.1µg/ml) for 4 days. Culture of human EGC from control patients (CONT) were obtained from surgical specimens. They were treated with supernatant from colonic biopsies at the concentration of 5% in a serum free medium. Supernantants were obtained after incubation of each colonic biopsie from IBD patient (I area and NI areas biopsies). Expression of the glial markers Sox10, S100β and glial fibrillary acid protein (GFAP) were assessed by quantitative real time PCR and Western blot analysis.

Results: Concerning the biopsies, the mRNA expression levels of Sox 10 and S100β were significantly elevated in I and NI areas of CD patients compared to UC patients (p < 0.001) and to CONT patients (p < 0.001). Intermediate isoform of GFAP was increased in inflamed area of CD patients compared to controls (p < 0.05). TI treatment of EGC from rats induced a significant over-expression of the three glial markers. LPS stimulation of EGC from rats also induced an over-expression of Sox10 and S100β but did not affect GFAP expression. We have not reproduced the increased expression of Sox 10 and S100β mRNA expression by human EGC treatment with supernantant from colonic biopsies of CD patient.

Conclusion: Our work shows that GFAP expression was differentially regulated by inflammatory cytokines and endotoxins. Ex vivo, LPS treatment reproduces the over-expression of Sox 10 and S100β in EGC cultures from rats, as observed in vivo in colonic biopsies of CD patients. However, treatment of human EGC in a primary culture with supernatant obtained from these biopsies, did not change the glial marker expression in human EGC .

Disclosure of Interest: None declared

P0912 INTRALUMINAL INFUSION OF MESENCHYMAL STROMAL CELLS IN SPHEROIDS ATTENUATES EXPERIMENTAL COLITIS

M. C. Barnhoorn¹, I. Molendijk¹, E. S. M. de Jonge-Muller¹, M. A. C. Mieremet-Ooms¹, J. J. van der Reijden¹, D. van der Helm¹, D. W. Hommes¹², A. E. van der Meulen-de Jong¹, H. W. Verspaget¹

¹Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, Netherlands, ²Division of Digestive Diseases, University of California Los Angeles, Los Angeles, United States

Contact E-mail Address: m.c.barnhoorn@lumc.nl

Introduction: Mesenchymal stromal cells (MSCs) have emerged as a promising therapeutic option for various diseases due to their immunomodulatory properties and ability to actively participate in tissue repair processes. However, these abilities are not intrinsic and therefore different strategies to induce and enhance their beneficial effects are currently under investigation. Recently, we observed that intraperitoneally injected MSCs settled as spherical shaped clusters, i.e. spheroids, onto the serosal fat surrounding the colon in experimental colitis.

Aims & Methods: In the present study we assessed whether luminal administration of MSCs in spheroids has a therapeutic effect. We infused 200 or 800 in vitro generated MSC spheroids, each consisting of 2,500 MSCs, intraluminally in C57BL/6 mice with established dextran sulphate sodium (DSS)-induced colitis. Body weight was measured daily and disease score consisting of the presence of loose stool, visible faecal blood and macroscopic inflammation was determined at sacrifice. Endoscopy was performed to evaluate mucosal damage and subsequent healing. Mucosal cytokine levels were measured in the homogenates of distal colon. In addition, myeloperoxidase activity in the homogenates of distal colon was measured as an index for neutrophil infiltration. Furthermore, we counted the number of macrophages in the lamina propria of the distal colon.

Results: MSC spheroids alleviated DSS-induced colitis when infused intraluminally resulting in less body weight reduction (9.2% after treatment with 800 MSC spheroids versus 16.4% and 15.9% after treatment with 200 MSC spheroids and PBS-treated mice, respectively; both p = 0.02), a lower endoscopic activity score and lower disease activity scores at sacrifice, related to the dose of MSC spheroids infused. Mucosal cytokine levels of interleukin-6 and interferon-gamma as well as numbers of macrophages and neutrophils in the distal colons were decreased particularly after intraluminal infusion of the high dose MSC spheroids.

Conclusion: Intraluminally infused MSC spheroids promote mucosal wound healing and attenuate experimental colitis, accompanied by less phagocytes and proinflammmatory cytokines in the mucosa.

Disclosure of Interest: None declared

P0913 ALTERED TISSUE GLUCOCRTICOID METABOLISM IS ASSOCIATED WITH INFLAMMATORY BOWEL DISEASE

M. Hussey¹, A. Cannon², G. Holleran¹, B. Hall¹, C. Kiat¹, J. O'Sullivan², M. Sherlock³, D. McNamara¹

¹Gastroenterology, Adelaide and Meath Hospital, Tallaght, Trinity Academic Gastroenterology Group, ²surgery, St. James's Hospital, Trinity College Dublin, ³Endocrinology, Adelaide and Meath Hospital, Tallaght, Dublin, Ireland

Contact E-mail Address: mhussey@tcd.ie

Introduction: Glucocorticoids (GCS) are known to modulate a number of immunological responses. Within tissues expressing glucocorticoid and mineralocorticoid receptors including the colon, GCS metabolism is regulated by the isozymes of 11 beta hydroxysteroid dehydrogenase (11βHSD). 11βHSD 1 acts as an oxoreductase, converting inactive cortisone into active cortisol while 11βHSD 2 acts as a dehydrogenase producing cortisone. Variations in expression may have a role in Inflammatory Bowel Disease (IBD).

Aims & Methods: To examine the expression of 11βHSD 1 & 2 in IBD.

Following informed consent, patients with known IBD aged 18-80yrs were recruited; exclusion criteria (1) Steroid ≤6 weeks, (2) Coagulopathy, (3) Pregnancy, (4) Cushing/Conns Syndrome (5) Quiescent disease. Disease activity was assessed using biochemical (C Reactive Protein (CRP)), clinical (Harvey-Bradshaw Index/Mayo Score) & histological parameters. Controls with a normal colonoscopy without a history of IBD were also recruited. Two additional biopsies were obtained including inflamed & non-inflamed samples from IBD patients where possible, whereas a single additional colonic biopsy was obtained from controls. Biopsies were stored in RNA later & analyzed in batch, using Quantitative real time RT-PCR (TaqMan) & commercially available Probes & Primers (Invitrogen). Relative transcript levels were determined using 18S as a reference gene. Relative expression of 11βHSD 1 & 2 were expressed as a mean and compared between groups using a student t test and 11βHSD 1:2 ratios were calculated and compared between groups using a Mann-Whitney U test with a p value of <0.05 considered significant.

Results: To date 28 IBD (16 Crohn’s Colitis and 12 Ulcerative Colitis) and 15 control patients have been recruited. IBD and control cohorts were demographically similar with 55% (n= 15) vs. 67% (n=10) being female, with a mean age of 45 years (17-76 years) and 55 years (19-70 years) respectively. Overall based on histology 46% (n=13) had mild disease, 43% (n=12) had moderate disease and 11% (n=3) had severe disease. In all 68% (n=19) and 57% (n=16) had elevations in their HBI/Mayo scores (HBI range 0-21, Mayo 0-12) and CRP (range 1-192.5mg/l) respectively. Overall mean levels of 11βHSD1 in IBD patients and controls were 197 au and 261 au respectively and were not significantly different while mean 11βHSD2 expression levels were significantly lower in IBD patients vs. controls (35 au vs. 176 au, p=0.001, 95% CI -226- -57.8). Of interest 11βHSD1:2 ratios were much higher in patients with IBD compared with controls (52:1 vs. 1.6: 1, p=0.001). Overall within the IBD cohort disease activity did not affect 11βHSD1 or 2 levels, however among IBD subjects with matched histological inflamed and non inflamed tissue samples (n=15) there was a trend towards lower 11βHSD2 levels (51au vs. 10 au, p=0.051).

Conclusion: Patients with IBD have altered glucocorticoid metabolism with increase 11βHSD1: 11βHSD2 ratios mainly due to a reduction in 11βHSD2 expression. Further work on 11βHSD2 regulation is warranted and may represent a novel therapeutic pathway in IBD patients.

Disclosure of Interest: None declared

P0914 LOW-DOSE LINDANE INGESTION AGGRAVATES SUSCEPTIBILITY TO COLONIC AND INTESTINAL INFLAMMATION IN MICE MODELS OF CROHN’S DISEASE

M. Body-Malapel¹, M. Djouina¹, P. Desreumaux¹, C. Gower-Rousseau¹, C. Vignal¹

¹Lille Inflammation Research International Center, UMR 995 INSERM, Lille University, CHRU, Lille, France

Contact E-mail Address: mathildebody@gmail.com

Introduction: Lindane (LIN) is an organochlorine pesticide. Although LIN has not been used as insecticide in Europe and USA since the 1970s, it is still currently included in the constitution of more than 500 commercial products. In addition, LIN is still used in developing countries. Because of its bioaccumulation potential, LIN is found in high concentrations in environment and food chain. The main contamination way in humans is consumption of lipid-rich diet such as fish and dairy products.

Aims & Methods: Our aim was to assess the effects of oral intoxication with low doses of LIN on gut inflammation in 3 different murine models.

C57Bl6 males were exposed during 1 month to oral intoxication with LIN (0, 5 and 50 µg/kg bw/day). Then 2 types of colitis were induced, either by single intrarectal injection of Trinitro benzene sulfonic acid (TNBS, 100 mg/kg bw), or by oral administration of dextran sodium sulfate (DSS, 2.5%) during 9 days. Besides, enteritis was induced by single gavage of indomethacin (10 mg/kg bw). Then mice were euthanized and gut inflammation intensity was assessed by macroscopic, histological and molecular parameters.

Results: In TNBS-induced colitis, mice intoxicated with LIN showed colitis macroscopic scores significantly higher (+228 % at 5 µg/kg/j, p = 0.001, and +145 % at 50 µg/kg/j, p = 0.03) compared to untreated mice with colitis only. Myeloperoxidase activity in colon of intoxicated mice was significantly enhanced in the 2 groups treated with LIN compared to untreated mice (+588 %, p = 0.002 at 5 µg, and + 153 %, p = 0.003 at 50 µg). Colitis histological score and IL-1 b mRNA levels were also higher in colons of mice intoxicated with LIN, with a significant 160 % (p=0.03) and 762% (p=0.003) increase respectively at the dosage of 5 µg compared to untreated mice with colitis only. Similar results were obtained in DSS-induced colitis, as mice having received the 2 dosages of LIN showed an increase of their colon weight/size ratio of 121 and 128% for the dosages 5 et 50 µg (p = 0.005 and p = 0.001 respectively), and an increase of colon myeloperoxidase activity (+301 and 287 %, p = 0.0007 and p = 0.009 respectively). Mice intoxicated with 5 µg showed also a significant increase of colitis histological score and colon IL1-b mRNA levels (+177%, p = 0.01, and +762%, p = 0.01, respectively). Following indomethacin-induced enteritis, jejunum of mice exposed to 5 and 50 µg LIN showed a significant increase of lesions areas (+171% p=0.03 and +253% p=0.003), lesions numbers (+146%, p=0.008 and +180%, p=0.0002) and Il1-b mRNA levels (+192%, p=0.02, and +350%, p=0.04).

Conclusion: Oral intoxication with low doses of lindane induces an aggravation of gut inflammation in 2 murine models of colitis and in 1 model of enteritis. The role of this persistent organic pollutant in inflammatory bowel diseases deserves further investigations.

Disclosure of Interest: None declared

P0915 ALTERED MUCOSAL 5-HT SIGNALING IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

M. S. Shajib¹², J. J. Kim¹², T. Aziz², P. Moayyedi¹³, W. Reinisch¹³, J. K. Marshall¹³, W. I. Khan¹²

¹Farncombe Family Digestive Health Research Institute, ²Pathology & Molecular Medicine, ³Division of Gastroenterology, Department of Medicine, McMatser University, Hamilton, Canada

Introduction: The gastrointestinal (GI) tract is the largest producer of serotonin (5-hydroxytrptamine; 5-HT) in the human body. Enterochromaffin (EC) cells are the best characterized subset of enteric endocrine cells and are the main source of 5-HT in the gut; tryptophan hydroxylase (Tph)1 is the rate-limiting enzyme involved in the bio-synthesis of 5-HT by EC cells. The diverse effects of 5-HT on various GI functions is mediated by multiple 5-HT receptor subtypes present on a variety of cells in the gut. Previously, we have shown that mice which have significantly reduced gut 5-HT levels exhibit reduced severity of experimental colitis, while replenishing gut 5-HT increased the severity of colitis. These seminal findings identified 5-HT as a key molecule in the pathogenesis of experimental colitis, but further research is needed to translate these observations for clinical utilization. While there are segregated reports on the changes of different components of 5-HT signaling in inflammatory bowel disease (IBD), there is a lack of studies with thorough examination on the changes of 5-HT content and 5-HT receptors in IBD.

Aims & Methods: A comprehensive assessment of key elements of gut 5-HT signalling in patients with Crohn's disease (CD) with a view to validate 5-HT as a new target for improved therapeutic strategy in CD. This study was approved by the local ethics committee. Mucosal biopsies were collected from the colon of consenting patients with CD and from healthy controls (HC), undergoing routine colonoscopy for colorectal cancer. Inactive specimens were collected from CD patients in remission, or from non-inflamed regions of patient with active disease. Non-inflamed regions were designated as those without any endoscopic features of inflammation and at least 10 cm from any area of active inflammation. A pathologist unaware of the diagnosis performed histological evaluation of the biopsies collected (n=10, 11 and 8 from HC, inactive and active CD segments, respectively). Additionally, relative gene expression of Tph1, serotonin reuptake transporter (SERT) and 5-HT receptors (5-HTR₁, 5-HTR₃, 5-HTR₄; 5-HTR₇) were determined by quantitative polymerase chain reaction (qPCR).

Results: Histological evaluation of biopsies confirmed the macroscopic assessments of the endoscopist during sample collection. There was significant upregulation of Tph1 and downregulation of SERT expression in active CD samples compared to both inactive and control samples. Investigations into 5-HT receptor expression by qPCR revealed significant increases in 5-HTR_3A and 5-HTR₇ expression in active CD samples compared to inactive and control samples. 5-HTR₄ expression was significantly elevated in both active and inactive CD samples compared to control, irrespective of disease activity and 5-HTR_1A expression was minimal in all groups compared.

Conclusion: Our findings establish that increased inflammation in patients with CD is associated with alterations in various aspects of 5-HT signalling (5-HTR_3A, 5-HTR₇, 5-HTR₄, Tph1, and SERT). Given the emerging role of 5-HT as a powerful modulator of inflammation and immune response, a better understanding of 5-HT signaling in intestinal inflammation in CD may ultimately lead to effective strategies targeting this pathway in CD.

Disclosure of Interest: None declared

P0916 LINKING TLRS ACTIVATION BY THE MICROBIOTA WITH CHANGES IN SENSORY-RELATED MARKERS IN IBS PATIENTS AND RATS

M. Aguilera¹², A. Fanning¹, G. Moloney¹, E. Quigley¹³, F. Shanahan¹³, K. Nally¹, S. Melgar¹, V. Martinez²

¹Alimentary Pharmabiotic Centre, University College Cork, Ireland, ²Cell Biology, Physiology & Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain, ³Department of Medicine, University College Cork, Cork, Ireland

Contact E-mail Address: monica.aguilerap@gmail.com

Introduction: Visceral pain is a hallmark of Irritable Bowel Syndrome (IBS). Dysbiotic states of the gut microbiota and alterations in host-bacterial interaction systems appear to contribute to the pathology of IBS. However, the exact mechanisms underlying these pathways are unknown.^1,2,3

Aims & Methods: The aim of this study was to investigate the relationship between the intestinal nociceptive system and Toll-like receptors (TLRs) in colonic tissue of IBS patients and to assess if this relationship is also altered when simulating a dysbiosis due to TLR-hyper-stimulation in rats. The expression of sensory-related [cannabinoid receptor 1 (CB1) and 2 (CB2) and vanilloid receptor type 1 (TRPV1)] and host-bacterial interaction markers (TLR2, TLR4, TLR5, TLR7) and antimicrobial peptides (AMPs, defensins) in sigmoidal colonic biopsies of IBS patients (n=12) and healthy controls (n=11) was assessed (qRTPCR). Additionally, Sprague Dawley male rats were treated intracolonically with a TLR4 agonist (LPS, Escherichia coli O5:B55, 0.2 mg/rat) or a TLR7 agonist [Imiquimod (IMQ), 0.1 mg/rat], (n=6 each group) for 5 days. Colons were collected for analysis of sensory markers, TLRs, AMPs and cytokines (qRT-PCR), quantification of secretory-IgA levels (s-IgA; ELISA) and histopathological analysis.

Results: Colonic biopsies of IBS patients showed a significant up-regulation of CB1 and CB2 (both P < 0.001), TRPV1 (P < 0.05) and TLR2 and TLR7 (both P < 0.001) expression when compared to healthy individuals. CB1, CB2 and TRPV1expression positively correlated with TLR2 and 7 expression in IBS patients (P < 0.001 in all cases). Minor changes were seen in the expression of TLR4, TLR5 and defensin 5.

Using TLR4 and 7 agonists to mimic a dysbiotic state in rats and the TLR-induced responses associated to IBS samples, we found that selective repetitive TLR stimulation induced a mild colonic immune activation characterized by an increase of pro- and anti-inflammatory cytokines expression and changes in levels of s-IgA without overt histological changes, compatible with features associated to IBS. Both TLR agonists also up-regulated the colonic expression of host TLRs (TLR2 > TLR7 > TLR5 > TLR4). Moreover, intracolonic instillation of LPS induced a significant increment in the colonic expression of CB1, CB2 and TRPV1, while IMQ down-regulated the expression of TRPV1. In general, higher changes were seen when stimulating with LPS when compared to IMQ. Similar to IBS biopsies, TLRs stimulation lead to minor changes in the expression of AMPs (defensins).

Conclusion: Altogether, our findings point towards an active communication between the microbiota and intestinal neuro-immune pathways, mainly by connecting the immune TLR-dependent signalling to the intestinal nociceptive system (endocannabinoid and vanilloid systems). Additionally, stimulation of TLRs by luminal factors (simulating dysbiosis) appears to be enough to induce intestinal immune and nociceptive signalling pathways which may be part of the underlying pathophysiological mechanisms of IBS, thereby linking the microbiota to intestinal neuro-immune pathways and visceral pain.

Disclosure of Interest: None declared

P0917 20 YEAR FOLLOW UP OF BRITISH TWIN PAIRS WITH INFLAMMATORY BOWEL DISEASE

H. Gordon¹, T. Orchard², S. Ng³, A. Steel¹, A. Cocker⁴, M. Harbord⁵

¹Gastroenterology, Chelsea and Westminster Hospital, ²Gastroenterology, St Mary's Hospital, London, United Kingdom, ³Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, Hong Kong, ⁴SSAT, Chelsea and Westminster Hospital, ⁵Gastroenterology, Chelsea and Westminster, London, United Kingdom

Contact E-mail Address: hannahgordon@doctors.org.uk

Introduction: IBD twin studies have shown similar disease phenotype within concordant pairs. Longitudinal follow up suggests pairs with CD remain concordant for location whereas twins with UC diverge (1). This study is a retrospective longitudinal analysis of UK twin pairs with IBD.

Aims & Methods: The UK IBD Twin and Multiplex Registry was searched for twin pairs who took part in a previous twin study. Data from 1994 and 2014 was reviewed. The following were analysed: zygosity, concordance, Montreal classification, admissions, surgical history.

Results: The UK IBD Twin and Multiplex Registry was searched for twin pairs who took part in a previous twin study. Data from 1994 and 2014 was reviewed. The following were analysed: zygosity, concordance, Montreal classification, admissions, surgical history.

Results

Demographics: N=94 twin pairs. UC:CD 48:46. Mean age 59.

Pair Concordance:

	CD 1994	CD 2014	UC 1994	UC 2014
MZ	33.3% (4:12)	41.7% (5:12)	21.4% (3:14)	21.4% (3:14)
DZ	9.1% (3:33)	9.1% (3:33)	11.4% (4:35)	17.1% (6:35)

3 previously discordant pairs became concordant. The mean time between diagnosis was 9.1 years.

Montreal Classification

Concordant Pairs: There were no mixed CD:UC pairs. Of the 17 concordant pairs, 10 had complete information from both twins in both datasets.

IBD: A was identical in 6/12 (50%) concordant pairs.

CD: L was identical in 3/6 (50%) pairs in both 1994 and 2014. B was only available from 2014, and was identical in 3/6 (50%) pairs. P was identical in 2/5 (40%) twins in 1994 and 3/7 (43%) twins in 2014.

UC: A was identical in 3/4 pairs (74%). L was identical in 4/4 (100%) pairs in 1994 and 2014.

All IBD sufferers

UC: Disease classified as proctitis decreased from 1994 to 2014 (30.4% vs 17.9%), with a corresponding increase in pancolitis (41.1% vs 50%)

CD: Cases classified as L3 increased from 6/52 (11.5%) to 22/53 (41.5%). Presence of perianal disease also increased (9.6% vs 23.1%).

Extraluminal manifestations increased from 4/109 (3.7%) to 13/112 (11.6%).

Surgery

Concordant pairs: Concordant twin pairs were concordant for history of previous surgery in 9/12 (75%) pairs in 1994 and 7/14 (50%) pairs in 2014.

All IBD: In 1994 32/109 (29.4%) IBD sufferers had undergone surgery, increasing to 52/112 (49.1%) in 2014.

Admission

Concordant pairs: Concordant twins were concordant for history of admission in 10/14 (71.4%) pairs in 1994 and 10/15 (66.7%) pairs in 2014.

All IBD: 46/109 (42.2%) IBD sufferers had at least one admission in 1994; this increased to 76/112 (67.9%) in 2014.

Conclusion: Pair concordance of this cohort supports that heritability of CD is greater than UC. Within concordant pairs with CD, disease location is less correlated than in other cohorts. Conversely, concordant pairs within UC were more similar and converged over time. Sample size limited analysis. Disease progressed over time.

Disclosure of Interest: None declared

P0918 RISING INCIDENCE OF INFLAMMATORY BOWEL DISEASE IN CANTERBURY, NEW ZEALAND

H. Su¹, V. Gupta², A. S. Day³⁴, R. B. Gearry¹²

¹Department of Gastroenterology, Christchurch Hospital, ²Department of Medicine, ³Department of Paediatrics, University of Otago, ⁴Department of Paediatrics, Christchurch Hospital, Christchurch, New Zealand

Contact E-mail Address: heidisu@hotmail.com

Introduction: A population-based study of inflammatory bowel disease (IBD) in the Canterbury province of New Zealand demonstrated an incidence of Crohn's disease (CD) in this region of 16.5 per 100,000 population in 2004, along with a high rate of IBD overall. At the time, this was one of the highest rates of CD in the world.

Aims & Methods: The current study aimed to ascertain the incidence of IBD in the same geographical area of New Zealand ten years later (during the 2014 calendar year). Patients diagnosed with IBD between January 1^st 2014 and December 31^st 2014 within the Canterbury region in the private and public sectors were identified and characterised. Diagnosis and disease classification was ascertained using standard accepted criteria. Projected population data for age and gender for the region were utilised to calculate incidence rates for IBD overall and for CD, ulcerative colitis (UC) and inflammatory bowel disease-unclassified (IBDU). Incidence rates were also age-standardized using the World Health Organization Standard Population. Furthermore, all patients were phenotyped according to the Montreal Classification.

Results: During the 2014 year, 205 patients were diagnosed with IBD in Canterbury. This group comprised 134 patients with CD, 69 with UC and 2 with IBDU. Patients were aged between 5 and 88 years, with most patients with CD and UC diagnosed between 20 and 54 years of age. The crude incidence rate for IBD for 2014 was 39.8 per 100,000 (95% CI, 34.4 – 45.3). In addition, the incidence rates for CD was 26.0 (95% CI, 21.6 – 30.4), for UC 13.4 (95% CI, 10.2 – 16.6), and for IBDU 0.39 (95% CI, -0.15 – 0.93) per 100,000 population. For patients with CD, disease location was evenly distributed (ileal 30%, colonic 36% and ileocolonic 34%) and 94% had inflammatory disease, with only 6% having stricturing or penetrating disease at diagnosis. Twenty-two percent of patients with CD had upper gut involvement, whilst 13% had perianal disease at diagnosis. Similarly, patients with UC had even distribution of pancolonic, left-sided and proctitis.

Conclusion: This population-based study demonstrates further substantial increases in the incidence of IBD in this well-delineated area of New Zealand. Overall, incidence rates were 1.5 fold greater than when assessed ten years earlier, with an even greater increase in the incidence of UC. The reasons contributing to these continued increases remain unclear. However, further increases in rates of IBD indicate growing health system demands in the coming years.

Disclosure of Interest: None declared

P0919 NEOPLASIA RISK AFTER COLECTOMY IN INFLAMMATORY BOWEL DISEASE PATIENTS – A SYSTEMATIC REVIEW AND META-ANALYSIS

L. A. Derikx¹, L. H. Nissen¹, L. J. Smits¹, B. Shen², F. Hoentjen¹

¹Gastroenterology and Hepatology, Radboud university medical centre, Nijmegen, Netherlands, ²Gastroenterology and Hepatology, Cleveland clinic, Cleveland, United States

Contact E-mail Address: Lauranne.Derikx@radboudumc.nl

Introduction: Although colectomy substantially reduces the risk to develop colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients, neoplasia may still develop following colectomy in the residual rectum or ileal pouch. Conclusive data regarding this risk are scarce, which has resulted in the absence of evidence-based postoperative endoscopic surveillance recommendations. We therefore conducted a systematic review and meta-analysis in order to determine prevalence, incidence, and risk factors for neoplasia development in the different post-surgical scenarios after colectomy, including: 1. patients with a permanent end ileostomy and rectal stump, 2. patients with an ileorectal anastomosis (IRA) 3. patients with an ileal pouch-anal anastomosis (IPAA).

Aims & Methods: PubMed, Embase, Web of Science and Cochrane Library were searched to identify studies which reported prevalences or incidences of colorectal neoplasia following colectomy or specifically assessed risk factors for neoplasia development. Two researchers independently performed study selection, quality assessment and data extraction. Prevalence’s were pooled and compared across subgroups with a logistic regression model. Risk factors were analyzed in a pooled random effect model, if possible, or otherwise critically appraised.

Results: Thirteen, 35 and 33 articles, including 1011, 2762 and 8403 patients, for respectively the rectal stump, IRA and IPAA group, were included for prevalence and incidence calculations. CRC prevalence following colectomy was significantly higher in the rectal stump group (2.1%, 95% CI 1.3-3.0) and IRA group (2.4%, 95% CI 1.7-3) compared to the IPAA group (0.46%, 95% confidence interval (CI) 0.32-0.61), with an odds ratio (OR) of 6.4 (95% CI 4.33-9.50). In the IPAA group, the pooled cumulative incidence of pouch/cuff carcinoma 25 years after IPAA construction was 3.4%. A history of CRC was the most important risk factor (IRA: OR 12.8, 95% CI 3.3-49.2; IPAA: OR 15.0, 95% CI 6.6-34.4). Furthermore, IBD duration and ulcerative colitis rather than a diagnosis of Crohn’s disease (OR 10.2) emerged as risk factors for rectum or pouch neoplasia.

Conclusion: The calculated prevalence and incidence for colorectal neoplasia following colectomy appeared relatively low, especially in the IPAA group. Major determinants for cancer development following colectomy were the presence of a residual rectum with a 6.4-fold increased risk, and a CRC-history with a 15.0- (IPAA) or 12.8-fold (IRA) increased risk. These findings may aid in developing individualized post surgical endoscopic surveillance strategies in order to optimize prevention of CRC in this patient population.

Disclosure of Interest: None declared

P0920 THE IMPACT OF GENDER ON WORK ACTIVITY IMPAIRMENT AND QUALITY OF LIFE IN INFLAMMATORY BOWEL DISEASE (IBD) IN SOUTHERN ITALY

M. Cappello¹, M. Mazza¹, R. Alloro¹, M. Mendolaro¹, P. L. Almasio¹, A. Craxì¹

¹Di.Bi.Mis - University of Palermo - Italy, UOC Gastroenterologia Ed Epatologia, Palermo, Italy

Contact E-mail Address: cmarica@tin.it

Introduction: IBD impact on patients’ major life activities, such as school, work, self-care, and quality of life. Published literature has reported higher rate of unemployment, sickleave and working disability. Data on gender influence are scanty, especially in Mediterranean countries.

Aims & Methods: Aim of our study was to compare work activity impairment and quality of life between female and male patients with IBD followed-up in a referral center from southern Italy. 102 patients with IBD (53 females, 49 males) consecutively observed in the IBD clinic were recruited. Data on clinical and demographic characteristics (age, type of IBD, disease behavior (Montreal) and activity (HBI, Mayo score), smoking habits, familial predisposition, current treatment, educational and marital status, current employment) were registered on a dedicated database. All patients agreed to fill in the WPAI (Work Productivity and Activity Impairment) questionnaire and the EQol-5D (European Quality of Life – 5Dimension) VAS scale.Data of the National Institute of Statistics (ISTAT) on employmentrates in Italy were used for comparison.

Results: There were no significant differences between males and females regarding age, educational and marital status and disease characteristics except disease activity rate, which was higher in males. There was a significant difference in the employment status since 58.5% of women were unemployed versus 34.7% of men (p=0.02). Overall, there were no differences in WPAI scores (absenteeism, presenteism, overall work and regular activities impairment) and EQoL between males and females. In male patients with active disease absenteeism (p=0.04), presenteism (p=0.02) and work productivity impairment (p=0.04) rates were significantly higher as compared to patients in remission, quality of life was not affected, in females with active disease we observed a higher rate of absenteeism (p=0.04) and impaired daily regular activities (p=0.04) as well as quality of life (p=0.015).

Conclusion: Gender significantly influences occupational status in IBD, since women are more often unemployed. Work productivity is impaired in both men and women with active disease, but in women daily regular activities and quality of life are more significantly affected than in men. These data, if confirmed in other geographical areas, should be kept in mind in clinical management of IBD female patients.

Disclosure of Interest: None declared

P0921 COLONIC METAPLASIA OF THE ILEUM AS A PREDICTIVE MARKER OF CLINICAL RELAPSE AFTER ILEO-COLONIC RESECTION FOR CROHN’S DISEASE: A PROSPECTIVE STUDY AT 4 YEARS

M. Ascolani¹, C. Mescoli², S. Onali¹, E. Calabrese¹, E. Lolli¹, A. Ruffa¹, G. Sica³, G. Palmieri⁴, F. Pallone¹, M. Rugge², L. Biancone¹

¹Systems Medicine, University “Tor Vergata", Rome, Italy, Rome, ²Pathology Unit, Università di Padova, Padova, ³Department of Surgery, ⁴Pathology Unit, University “Tor Vergata", Rome, Italy, Rome, Italy

Contact E-mail Address: biancone@med.uniroma2.it

Introduction: Colonic metaplasia of ileum has been reported in Crohn’s Disease (IBD), particularly in severe/established ileal lesions. Differently, CD ileum with no lesions or with early post-operative recurrence showed to express the small intestine type mucin phenotype (1).

Aims & Methods: In a prospective study at 4 years, we aimed to address whether colonic metaplasia of the ileum may represent a marker of clinical relapse after ileo-colonic resection for CD. At this purpose, a cohort of CD patients (pts.) already followed up for 1 year (1), was clinically followed up for additional 3 years after surgery. Clinical recurrence at 4 years was assessed in the same cohort of 19 CD pts. with recurrence and colonic metaplasia assessed at 6 (T1) and 12 months (mos) (T2)(1). In the same pts. colonic metaplasia of the ileum was already evaluated at surgery (T0), at T1 and T2 (1). The expression of sulfomucins (colon phenotype) and sialomucins (small intestine mucin and phenotype) in the ileum was evaluated by immunohistochemistry (1). In the present study, compliant CD pts. were followed up for 4 years after surgery, with clinical recurrence (CDAI > 150) assessed yearly. The correlation between the percentage of expression of sulphomucin and clinical recurrence at4 years was assessed. Statistic: Results were expressed as median (range). Coefficient of correlation, the unpaired T test used as appropriate.

Results: Clinical follow up at 4 yrs was completed by 17 CD pts. (12 males, age 41 yrs, range 17-57). Endoscopic recurrence occurred in 13/17 pts. at T1 and in 14/17 pts. at T2. (median: T1: 2., range 0-4; at T2: 0, range 0-4). Clinical recurrence was assessed at 6 mos, 1.2.3 and 4years (pts. n=1, 3, 3, 2, 1, respectively). A significant correlation was observed between the percentage of expression of sulphomucin in the ileal surgical samples and the CDAI at 4 yrs (r=0.62 p=0.007), but not at 6 mos, 1, 2 or 3 yrs. A significant correlation was also observed between the percentage of expression of sulphomucin in the ileal biopsies at 6 mos and the CDAI at 6 mos (r=0.68; p=0.003), but not at 1, 2, 3 and, 4 yrs. The percentage of expression of sulphomucin in the ileal biopsies at 12 mos was significantly correlated with the CDAI at 2 yrs (r=0.53; p=0.02). The median expression of sulphomucins in the ileal surgical samples was significantly higher in the subgroup of pts. developing clinical recurrence at 2 yrs. (40, 10-99 vs 5, 0-50; p=0.04), but not at the other observations. The median expression of sulphomucins in the ileal samples at 12 mos was higher in the subgroup of pts. developing clinical recurrence at 1 and 2 yrs (median, range: 30, 1-40 vs 0, 0-35; p=0.025 and 30, 0-40 vs 0, 0-35; p=0.029, respectively), but not at 3 yrs (15, 0-30 vs 0, 0-40; p=n.s.).

Conclusion: In CD ileum, the development of a “metaplastic” colonic-mucosa phenotype, as observed in the surgical specimens and in severe early post-operative recurrence, may represent a predictive marker of clinical relapse in pts under regular follow up after ileo-colonic resection.

Disclosure of Interest: M. Ascolani: None declared, C. Mescoli: None declared, S. Onali: None declared, E. Calabrese Lecture fee(s): MSD, Abbvie, E. Lolli: None declared, A. Ruffa: None declared, G. Sica: None declared, G. Palmieri Lecture fee(s): Zambon, Takeda, F. Pallone Lecture fee(s): Zambon, Takeda, M. Rugge: None declared, L. Biancone Lecture fee(s): MSD, Takeda, Abbvie, Zambon, A

P0922 SMALL BOWEL CANCER ASSOCIATED WITH CROHN’S DISEASE

M. Shinozaki¹

¹Surgery, University of Tokyo, Tokyo, Japan

Contact E-mail Address: mshino-tky@umin.ac.jp

Introduction: Population-based studies revealed that patients with Crohn’s disease (CD) have increased risk of developing small bowel cancer in comparison with the background population. However, little is known concerning to the cancer in detail, because the number of the patients are relatively small.

Aims & Methods: This study aimed to clarify the clinicopathological characteristics between small bowel cancer and colorectal cancer in CD.

We performed a literature search in Ichushi (Japanese medical literature database) between 1983 and March, 2015 for small bowel cancer and colorectal cancer associated with CD. Two hundred and seventy-one cases were picked up, and we excluded six cases, because the location of the cancer was not specified clearly. Thus, 265 cases were included in this study. The cases were classified to two groups: patients who had small bowel cancer(s) (S group: n=55) and those with only colorectal cancer(s) (C group: n=210), which included perianal fistula cancer.

Results: The age at cancer diagnosis was higher in S group (53.5 (29-81); median (range)) than in C group (43 (25-89); p < 0.0001). The duration of CD was similar between S group (16 (0-40) years) and C group (15 (0-52) years; p=0.41). The age at CD diagnosis was also higher in S group (39(12-69)) compared with C group (25 (9-84)). S group had more proportion of ileitis than C group (58% vs. 10%), whereas 81% of the patients in C group had ileocolitis, and the difference was statistically significant (p < 0.0001). In S group, the cancer diagnosis was made before treatment only in 16%, and 70% of these patients had not been diagnosed before pathological examination of the resected specimen. Well differentiated and moderately differentiated adenocarcinoma occupied three quarters of the tumor in S group whereas only 44% in C group (p < 0.0001). On the other hand, the proportion of mucinous carcinoma was only 4% in S group, and that was 40% in C group (p < 0.0001). The clinical stage according to the Union for International Cancer Control classification was 4%/8%/39%/12%/39% (stage 0/1/2/3/4) in S group, and that was 3%/14%/35%/29%/19% in C group, and the proportion of stage 4 was significantly higher in S group. Although the resection rate was higher in S group than in C group (98% vs. 87%; p=0.0055), the prognosis was equivalent (41% were alive in S group and 44% in C group).

Conclusion: We found some differences between the two groups with regard to the age at cancer detection, the age at CD onset, the timing of cancer diagnosis, the histology of the cancer, and clinical stage of the cancer. We should always give attention not to miss small bowel cancer at CD operation.

Disclosure of Interest: None declared

P0923 NATURAL HISTORY OF CROHN’S DISEASE IN ELDERLY PATIENTS DIAGNOSED OVER THE AGE OF 70 YEARS: A POPULATION-BASED STUDY

M. Fumery¹, H. Sarter², B. Pariente³, C. Charpentier⁴, L. Armengol Debeir⁴, J.-L. Dupas¹, L. Peyrin-biroulet⁵, C. Gower-Rousseau⁶, G. Savoye⁴, on behalf of EPIMAD

¹Amiens University Hospital, Amiens, ²Epimad Registry, EA 2694, Biostatistic Unit, ³Lille University Hospital, lille, ⁴Rouen University Hospital, Rouen, ⁵Nancy University Hospital, Nancy, ⁶Epidemiology Unit, Epimad Registry, Lille University Hospital, Lille, France

Contact E-mail Address: mathurinfumery@gmail.com

Introduction: Elderly-onset (>60 years at diagnosis) Crohn's disease (CD) seems to be associated with a better outcome than CD diagnosed earlier in life.

Aims & Methods: Our aim was to compare the natural history of CD in elderly patients older than 70 years (y) at diagnosis with that of elderly patients diagnosed between the age of 60 and 70 y in the EPIMAD population-based registry. Three-hundred and seventy patients with elderly-onset CD diagnosed between January 1988 and December 2006 were identified. Among them, 188 (63%) were older than 70 y at diagnosis. Characteristics at diagnosis as well as natural history, surgery needs and drug exposure were recorded with a median follow up of respectively 4.5 y [1.1;8.3] in CD diagnosed after 70 y and 7.8 years [3.3;12.1] in CD diagnosed between 60 and 70 y.

Results: CD incidence in patients older than 70 y was 2.3/100 000 inhabitants. The proportion of males was lower in patients diagnosed after 70 y than in those diagnosed between 60 and 70 y (31% vs 45%, p=0.006). Clinical presentation at diagnosis was similar in both groups with respect to symptoms as bloody stools, perianal location and extra-intestinal manifestations. Pure colonic location (L2) was more frequent among patients > 70 y both at diagnosis (73% vs 57%, p=0.004) and maximal follow-up (70% vs 47%, p < 0.0001). Disease extension (from L1 or L2, to L3) was less frequent in patients > 70 y (7% to 15%, p=0.03). The most frequent behavior in the two groups was inflammatory both at diagnosis (75% vs 80%, p=0.43) and maximal follow up (69 vs 70%, p=0.55). There was no significant difference in patients > 70 y compared to those between 60 and 70 y regarding treatment with 5ASA (71% vs 76%, p=0.27), oral corticosteroids (39% vs 45%, p=0.86), and anti-TNF (4% vs 7%, p=0.63). However, the use of immunosuppressants was significantly less frequent in patients > 70 y (12% vs 25%, p < 0.001). Risk for surgery was similar in both groups (29% vs 28% p=0.35).

Conclusion: Natural history of CD in elderly patients diagnosed over the age of 70 y seems to be milder than that in elderly patients diagnosed between 60 and 70 y. The exposure to immunosuppressants and biologics is low in patients diagnosed over 70 y with no difference in surgery needs. This needs to be taken into account when establishing therapeutic strategies.

Disclosure of Interest: None declared

P0924 DESCRIPTION OVER TIME AND STUDY OF ASSOCIATED FACTORS FOR THE DIAGNOSTIC DELAYIN CROHN’S DISEASE: A 21-YEAR POPULATION BASED STUDY

M. Collins¹², H. Sarter³, M. Fumery⁴, L. Armengol-Debeir⁵, E. Laberenne⁶, F. Vasseur⁷, D. Turck⁸, B. Pariente⁹, L. Dauchet⁷, L. Peyrin-Biroulet¹⁰, G. Savoye¹¹, C. Gower-Rousseau⁷, on behalf of EPIMAD

¹Gastroenterology Unit, University hospital, Lille, ²Gastroenterology Unit, Hôpital Bicêtre, Le Kremlin Bicêtre, ³Epidemiology, University hospital, Lille, ⁴Gastroenterology Unit, Amiens University hospital, Amiens, ⁵Gastroenterology Unit, Rouen University Hospital, Rouen, ⁶Gastroenterology Unit, Seclin Hospital, Seclin, ⁷Epidemiology, ⁸Pediatrics, ⁹Gastroenterology Unit, University Hospital Lille, Lille, ¹⁰Gastroenterology Unit, University HOspital Nancy, Nancy, ¹¹Gastroenterology Unit, University Hospital Rouen, Rouen, France

Contact E-mail Address: Corinne.GOWER@chru-lille.fr

Introduction: Delay in diagnosis (DD) of Crohn's disease (CD) may be responsible for complications and for poor response to treatment. The description of DD over time in a population-based CD cohort and its determining factors are unknown and may help implementing corrective measures. The aim of this study was to report in a 21-year population-based cohort the variation over time of DD and to identify associated factors including sociodemographic factors.

Aims & Methods: Sociodemographic and clinical characteristics of all CD patients issued from the EPIMAD registry and diagnosed from 1990 to 2010 were included. DD was defined as the time between onset of symptoms and CD diagnosis (months). DD was considered as long when in the upper quartile of this time period. Sociodemographic data included the living area of each patient at the time of diagnosis (urban, periurban or rural), the distance between the patient's living area and the nearest gastroenterologist, and the deprivation index of the living area (FDep99). Clinical data were classified according to the Montreal classification. Univariate and multivariate analyses were performed using a logistic regression to identify the baseline characteristics of patients associated with a long DD.

Results: 8,704 patients with CD were recorded including 57% of females; 10% of them had < 17 years at CD diagnosis (A1), 67% between 18 and 59 years (A2) and 23% >60 years (A3). The majority (65%) of patients had an ileocolonic CD and 5% had perianal lesions; 17% had a stricturing and 10% a penetrating behaviour. During the whole study period, median DD was 3 months [Q1=1; Q3=7] with no change over time. A long DD was >7 months and was associated in univariate analysis with the absence of weight loss (p=0.04), the presence of extra-intestinal manifestations (p=0.02), pure ileal involvement (L1) (p < 0.0001) and stricturing behaviour (p=0.002). In multivariate analysis, only the absence of weight loss (OR=1.16 [1.04-1.28]) and pure ileal location (OR=1.36 [1.18-1.56]) were associated with a long DD. Socioeconomic characteristics were not associated with a long DD.

Conclusion: In this 21-year population-based study of CD patients, median DD was 3 months with no change over time and no influence of socioeconomic baseline characteristics. Only two clinical features (absence of weight loss and L1 location) were associated with a long DD.

Disclosure of Interest: None declared

P0925 FACTORS THAT ARE ASSOCIATED WITH THE OCCURRENCE OF FISTULAE AND STENOSIS IN CROHN’S DISEASE PATIENTS IN THE SWISS IBD COHORT

J. Zeitz¹, C. Labenz¹, L. Biedermann¹, N. Fournier², P. Frei¹, B. Misselwitz¹, S. Scharl¹, S. R. Vavricka¹, M. Fried¹, G. Rogler¹, M. Scharl³, on behalf of Swiss IBD Cohort Study Group

¹University Hospital Zürich, Zürich, ²Centre Hospitalier Universitaire Vaudois, Lausanne, ³Division of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland

Introduction: Fistulae and stenosis represent a frequent and severe complication in Crohn’s disease (CD) patients. For an optimal treatment it is essential to identify factors being associated with the development of CD-associated fistulae and stenosis to guide the clinical management or, ideally, prevent their occurrence. Our study aimed to identify independent predictors of fistulae and stenosis in CD patients from the patient collective of the Swiss inflammatory bowel disease cohort study (SIBDCS).

Aims & Methods: We retrieved data of 1’600 CD patients (47.6% males, median age: 39ys) from the nationwide SIBDCS. The development of fistulae and stenosis in relation to smoking status, disease location, age at diagnosis, medications and history of intestinal resection surgery were analyzed.

Results: In the univariate analysis female gender was associated with a lower risk for perianal fistulae (OR 0.64; CI 0.48-0.86; p=0.003) while younger age at diagnosis of CD was associated with perianal (OR 0.98; CI 0.97-0.99; p=0.002 and OR 0.98; CI 0.97-0.99; p=0.002) and multiple fistulae (OR 0.98; CI 0.96-0.99; p=0.027 and OR 0.98; CI 0.96-0.99; p=0.035). Colonic and ileo-colonic manifestation at the time of initial CD diagnosis was associated with the occurrence of perianal or multiple fistula (OR 2.30; CI 1.41-3.77; p=0.001 and OR 2.18; CI 1.40-3.77; p=0.001). Independent factors that were associated with perianal fistulae by multivariate analysis were smoking at time of CD diagnosis (OR 1.508, CI 1.103-2.061, p=0.010), presence of stenosis (OR 1.422, CI 1.023-1.978, p=0.036), colonic (OR 2.505; CI 1.489-4.215, p=0.001) or ileo-colonic CD at diagnosis (OR 1.797 CI 1.137-2.844, p=0.012) and ever treatment with either antibiotics (OR 2.167, CI 1.594-2.945, p < 0.001) or anti-TNF antibodies (OR 2.296, CI 1.678-3.141, p< 0.001). The latter four aspects are also associated with the presence of multiple fistulae. Multiple fistulae are further associated with a history of intestinal resection (OR 3.098, CI 1.890-5.079, p < 0.001). Female gender protects form perianal fistulae (OR 0.571, CI 0.420-0.775, p < 0.001).

Colonic involvement at CD diagnosis (OR 0.531, CI 0.305-0.925, p < 0.026) protects from the onset of stenosis. History of intestinal resection (OR 6.476; CI 4.866-8.617, p < 0.001), anemia (OR 1.529; CI 1.106-2.115, p=0.010), presence of fistulae (OR 1.424; CI 1.075-1.887, p=0.014), disease duration per year (OR 1.018; CI 1.003-1.032, p=0.016) and treatment with antibiotics (OR 1.524; CI 1.167-1.990, p=0.002) or steroids (OR 1.756; CI 1.242-2.481, p=0.001) were independently associated with the occurrence of stenosis.

Conclusion: In particular markers of a severe disease course, such as younger age at diagnosis, history of intestinal resection, use of steroids or anti-TNF antibodies are associated with the occurrence of CD-associated fistulae and stenosis.

Disclosure of Interest: None declared

P0926 THE ROLE OF SMOKING IN THE NATURAL HISTORY OF CROHN’S DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS

N. To¹², D. Gracie¹², R. Pounder³, A. Ford¹²

¹Leeds Gastroenterology Institute, ²Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK., Leeds, ³Royal Free Hospital, and University College Medical School, London, United Kingdom

Contact E-mail Address: n.to@leeds.ac.uk

Introduction: There is strong evidence that smoking is a strong risk factor for the development of Crohn’s disease. The role of smoking on disease progression is less definitive. Some studies support the notion that it increases the risk of complications, resulting in more flares of disease activity and surgical intervention. However, the results of other studies are conflicting. We therefore conducted a systematic review and meta-analysis of current available data to examine this issue.

Aims & Methods: We carried out a search of MEDLINE, EMBASE and EMBASE. Eligible studies were cross-sectional surveys, cohort studies, or case-control studies examining the impact of smoking on the natural history of Crohn’s disease, defined according to clinical, radiological, histological, or endoscopic criteria in a minimum of 50 patients. Outcomes of interest were flares of disease activity, or need for surgery, according to smoking status. There were no language restrictions, and a recursive search of bibliographies of all eligible articles was performed. Two independent investigators judged eligibility and extracted data on each article, with a third investigator resolving any disagreements between the two. Study quality was assessed according to published criteria. Dichotomous data were pooled using a random effects model, and the association between smoking status and flare of disease activity, or need for surgery, was summarized using an odds ratio (OR) with a 95% confidence interval (CI).

Results: The search strategy identified 3374 citations, of which 164 appeared relevant to the study question, and were retrieved for further evaluation. Of these, 40 were eligible for inclusion, including a total of 2769 patients. Overall, 1243 (69.5%) of 1788 smokers had a flare of disease activity, compared with 1431 (64.3%) of 2225 non-smokers (OR = 1.56; 95% CI 1.21-2.01). Following a “curative” resection for Crohn’s, 165 (59.6%) of 277 smokers had a subsequent flare, compared with 138 (45.8%) of 301 non-smokers (OR = 1.66; 95% CI 0.99-2.79). There were 882 (33.1%) of 2661 smokers who required any surgery during follow-up, compared with 982 (30.4%) of 3235 non-smokers (OR = 1.19; 95% CI 0.99-1.44). When the association between smoking and need for first surgery was examined, there were 508 (51.4%) of 989 smokers who required a first operation, compared with 575 (30.5%) of 1883 non-smokers (OR = 1.71; 95% CI 1.30-2.41). Finally, in those who had undergone a first operation, 404 (47.5%) of 850 smokers underwent a second operation, compared with 276 (30.2%) of 913 non-smokers (OR = 1.61; 95% CI 1.40-1.85).

Conclusion: As has previously been described, smoking adversely impacts the natural history of Crohn’s disease, with a 56% increase in flares of disease activity during follow-up, and a 19% increase in need for surgery. First surgery rates are increased by 71% in smokers, and reoperation rates after first surgery by 61%. Smoking cessation interventions should be implemented in all patients with Crohn’s disease who smoke.

Disclosure of Interest: None declared

P0927 MOTIVATIONAL INTERVIEWING IN INFLAMMATORY BOWEL DISEASE PATIENTS COUNSELLING: DATA FROM A LARGE CASE-CONTROL STUDY

F. Mocciaro¹, R. Di Mitri¹, F. Bossa², D. Scimeca², G. Russo¹, G. M. Pecoraro¹, G. Biscaglia², G. Martino²

¹Gastroenterology and Endoscopy Unit, ARNAS Civico-Di Cristina-Benfratelli Hospital, Palermo, ²Division of Gastroenterology, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo (FG), Italy

Contact E-mail Address: fmocciaro@gmail.com

Introduction: Motivational interviewing (MI) is a patient-centered counselling also proven useful in inflammatory bowel disease patients. Some skills are at the base of a successful MI: the ability to ask open ended questions, the ability to provide affirmations, the capacity for reflective listening, and the ability to periodically provide summary statements to the patients.

Aims & Methods: We report data from a case-control study (1:1 ratio) on MI applied to IBD patients. Between June 2014 and March 2015 we collected data from 2 IBD referral centers both with knowledge on MI skills but only one of these (case group) currently applied this technique during the visits. At the end of visit all patients filled out an anonymous questionnaire.

Results: 200 patients (108 males [54%]) with a mean age of 40.3 ± 15.5 years were evaluated. Ninety-two patients were affected by Crohn's disease (46%), 96 by ulcerative colitis (48%), and 12 by indeterminate colitis (6%). Patients' characteristics were quite similar between case and controls: male 51% vs. 57%, mean age 35.5.1 ± 14.1 vs. 44 ± 15.1, Crohn’s disease 48% vs. 44%, ulcerative colitis 46% vs.50%, indeterminate colitis 6% vs. 6%. At final analysis 162 patients (81%) were previously evaluated by a gastroenterologist with an acceptable satisfaction rate (68%) which significantly decreased in those at the first outpatient visit (54%, p < 0.001). Satisfaction rate on general practitioner was low both in all patients and in those at the first visit (48% and 28%). The lowest satisfaction rate was reported in patients at the first visit (p < 0.001), in patients affected by indeterminate colitis (p=0.003), in patients with long disease duration (p=0.004); 78% of patients would have liked the use of explanatory pictures during the visits. Patients already followed-up in the referral centers reported a good overall satisfaction rate (87%) which reached 100% in those at the first visit. Nevertheless in the latter group, on a scale from 1 to 5, “5” (100% satisfied) was reported by 97% of patients on MI-group (case group) compared to 54% of controls: p < 0.001. No differences in terms “physician's communication skills", “perceived empathy” and duration of visits (41.9 ± 8.6 vs. 40.2 ± 9.4 minutes) were observed.

Conclusion: Our study showed as IBD patients followed-up in referral centers are satisfied of their physician rather than gastroenterologists without experience on IBD. MI is a communication tool very well appreciated by IBD patients and can help “IBD experts” to reach the best communication skills especially in pts at the first visit. Explanatory pictures should be used to help patients to better understand their clinical condition.

Disclosure of Interest: None declared

P0928 CONTRAST-ENHANCED ULTRASONOGRAPHY IN THE EVALUATION OF CROHN’S DISEASE ACTIVITY: CORRELATION WITH ILEOCOLONOSCOPY

F. Dias De Castro¹, J. Magalhães¹, P. Boal Carvalho¹, S. Monteiro¹, S. Leite¹, M. J. Moreira¹, J. Cotter¹²

¹Gastroenterology, Centro Hospitalar do Alto Ave – Guimarães, Portugal, Guimarães, ²Life and Health Sciences Research Institute, Universidade do Minho, Braga/Guimarães, Portugal

Contact E-mail Address: franciscadcastro@gmail.com

Introduction: The role of contrast-enhanced ultrasonography (CEUS) for assessing CD activity is still evolving.

Aims & Methods: Our aim was to determine the performance of conventional US and CEUS to detect CD activity assessed by ileocolonoscopy taken as the reference.

Thirty-five patients with small bowel CD were prospectively studied. Clinical disease activity was assessed by the Harvey–Bradshaw Index (HBI). All patients underwent ileocolonoscopy and also a conventional US followed by a CEUS using a microbubble contrast agent (SonoVue^®). US examinations was performed using a Hitachi HI VISION Avius®, employing a multi frequency convex abdominal transducer. Disease small bowel activity was assessed by ileocolonoscopy (reference) and patients were graded, for the purpose of statistical analysis, as inactive (normal or mild disease) or active (moderate or severe inflammation). Qualitative and quantitative parameters from the sonographic analysis included maximum bowel wall thickness, vascularity pattern by Doppler US and quantitative measurements of contrast bowel wall enhancement using CEUS (peak intensity and time to peak). Statistics were performed with SPSS v.20.0.

Results: Disease severity was as follow: no inflammation in 10 patients (29%), mild in 5 patients (14%), moderate in 4 patients (11%) and severe in 16 patients (46%). Only 6 patients (17%) had significant clinical activity (HBI ≥ 5 points). In patients with active endoscopic disease, wall bowel thickness of the terminal ileum was higher than in patients with inactive disease (7mm vs 5mm, p=0.029), the same association was observed for the presence of moderate to severe vascularity by Doppler (p=0.006). For CEUS the peak intensity was related with disease severity (10.5 vs 21.5, p=0.001) with an excellent capability to predict endoscopic activity in ileoscopy (area under the ROC curve 0.896, 95% CI 0.786-1.0). The time to peak could not predict endoscopic activity in ileoscopy (23.2 sec vs 22.7 sec, p=0.7).

Conclusion: Wall bowel thickness, Doppler US and CEUS peak intensity are valuable parameters for an accurate detection of small bowel inflammatory activity in CD. Conventional US and Contrast-enhanced US could in the future have a major role in the assessment of inflammatory activity in CD patients, and probably in the evaluation of therapeutic response.

Disclosure of Interest: None declared

P0929 CHANGE IN CLINICAL PRESENTATION OF IBD PATIENT ADMITTED TO THE HOSPITAL FROM EMERGENCY DEPARTMENT AND/OR OUTPATIENT CLINIC: RESULTS FROM A 1996-2013 RETROSPECTIVE STUDY FROM AN ITALIAN TERTIARY CENTER

F. Scaldaferri¹, M. T. Pistone¹, V. Ojetti¹, A. Poscia², L. R. Lopetuso¹, M. Volpe², E. Schiavoni¹, E. Gaetani¹, D. Mc Namara³, G. Cammarota¹, A. Gasbarrini¹, F. Franceschi¹

¹Internal Medicine Department, Gastroenterology Division, Catholic University of Sacred Heart of Rome, ²Institute of Hygiene, “Polyclinic A. Gemelli” Hospital, School of Medicine, Catholic University of the Sacred Hearth, Rome, Italy, ³Trinity College, Dublin, Ireland

Introduction: Recently a big change in management and organization of IBD patients occurred thought Europe, including Italy, because of introduction of anti-TNF-a, introduction of IBD units, etc. Few studies exist on clinical features of IBD admitted to hospital and its change during the time.

Aims & Methods: Aim of this study was to describe clinical presentation, outcome of hospitalization, need for surgery and complications of IBD patient admitted to the hospital from emergency or outpatient clinic. 5407 admissions from 1996 to 2013 at Policlinico “A. Gemelli” hospital were analyzed, identified from ICD-9-CM code referring to IBD. All records were classified to define: type of access (if from outpatient clinic or from emergency department); admission code if suspicion of IBD or flare or Complications or Unrelated Reason); diagnosis at the discharge according to ICD-9-CM; clinical outcome of the hospitalization if diagnosis/follow-up, Treatment, outcome not related; surgical outcome if no/ unrelated surgery, Related surgery, complications. Data are stratified for type of IBD, type of access, time (Pre vs. Post-biological, being the cut-off year 2003 for the CD and 2007 for the UC). Statistical analysis was performed by chi2 test for qualitative variables and the Student's t test for quantitative variables. Statistical significance was defined for p values less than 0.05.

Results: IBD represent around 1% of all admission to tertiary center. 557 out of 5407 patients (10.3%) were admitted for abdominal pain and were then diagnosed for IBD. Admission rate from emergency were 19 % ot total for both CD and UC, with a mean admission per patient of 2.5 ± 3.9 (min 1 and max 53 admissions). In CD patients complications were higher if admitted from emergency department while in UC higher if admitted from outpatient clinic; fistulas and obstruction were complication associated primarily to CD while bowel cancer and osteo-articular diseases for UC. Stratifying for admission before and after introduction of anti-TNF we observed an increase of admission for recurrence of the disease; an increase in medical and surgical treatments; an overall increase in complications, with a decrease of some important complications and the rise of extra-intestinal cancer in UC.

Conclusion: Clinical presentation, outcome of hospitalization, need for surgery and complications in IBD patient varied in recent years differently according to type of disease, type of admission at the hospital and also timeframe, being introduction of anti-TMF-a and re-organization of outpatient clinic major determinants of it. This is a starting point for a better cost-effective and integrated management of IBD.

Disclosure of Interest: None declared

P0930 HEALTH-RELATED QUALITY OF LIFE IN INFLAMMATORY BOWEL DISEASE IN SOUTH-EAST NORWAY 20 YEARS AFTER DIAGNOSIS

G. Huppertz-Hauss¹, M. L. Høivik², B. Moum², G. Hoff³, T. Bernklev³, on behalf of Inflammatory Bowel disease in South-East Norway - IBSEN group

¹Gastroenterology, Telemark Hospital, Skien, ²Gastroenterology, Oslo University Hospital, Oslo, ³Research and Development, Telemark Hospital, Skien, Norway

Contact E-mail Address: hhge@sthf.no

Introduction: Inflammatory bowel disease (IBD) can reduce patient’s health-related quality of life (HRQoL). The aim of the present study was to compare HRQoL in ulcerative colitis (UC) and Crohn’s disease (CD) 20 years after diagnosis with the background population, and to identify factors associated with reduced HRQoL.

Aims & Methods: IBD patients from a population-based inception cohort (IBSEN) were invited to a follow-up visit 20 years after diagnosis. In addition to a structured interview, clinical examination, blood and stool samples and a colonoscopy, patients answered the Short Form 36 (SF-36), the Norwegian Inflammatory Bowel Disease Questionnaire (N-IBDQ) and the Fatigue Questionnaire.

Results: 72% (438/604) of patients with a confirmed UC or CD diagnosis completed the HRQoL questionnaires. Females scored lower than males in SF-36 dimensions and N-IBDQ total scores, stratified by diagnosis (Table 1). Seven out of eight SF-36 dimensional scores were statistically significantly reduced compared to the Norwegian reference population. However, only the difference in the general health (GH) dimension between CD patients and the reference population (67.3 vs. 77.4) appeared to be of clinical importance with a z-score of 0.65, which is a moderate difference according to Cohen’s effect size. C-reactive protein >5, current symptoms and not working were independent factors associated with reduced scores in SF-36 dimensions in CD patients (CRP > 5: role physical (RP) 72 vs. 42, bodily pain (BP) 72 vs. 60, GH 66 vs. 54; current symptoms: RP 79 vs. 52, BP 80 vs. 61, GH 72 vs. 56, vitality (VT) 60 vs. 44, p < 0.01; not working: physical functioning (PF) and BP (91 vs. 76 and 78 vs. 57, p < 0.001)). In UC patients a simple clinical colitis activity index (SCCAI) > 2.5 and having chronic fatigue (CF) were associated with reduced SF-36 dimension scores (SCCAI: RP 81 vs. 48, BP 75 vs. 53, GH 72 vs. 53, VT 61 vs. 47; CF: PF 89 vs. 74, RP 80 vs. 45, BP 74 vs. 50, GH 72 vs. 51, VT 62 vs. 38, p< 0.01).

Table 1:

SF-36 dimensional scores and N-IBDQ total scores

UC			CD
	Male	Female		Male	Female
PF***	91 (88-93)	82 (79-85)	PF***	91 (87-96)	79 (74-83)
RP***	81 (75-87)	65 (59-71)	RP*	73 (64-82)	56 (47-65)
BP**	74 (70-78)	65 (61-69)	BP*	75 (69-80)	65 (59-71)
GH*	70 (67-74)	65 (61-69)	GH*	68 (63-73)	58 (53-63)
VT***	62 (59-66)	53 (50-56)	VT**	57 (52-62)	46 (40-51)
SF*	87 (83-90)	81 (77-84)	SF	83 (77-89)	75 (69-81)
RE**	87 (81-92)	74 (69-80)	RE	77 (68-86)	67 (58-77)
MH	81 (78-83)	78 (75-80)	MH*	80 (76-84)	72 (68-76)
N-IBDQ total  score**	187 (183-191)	178 (174-182)	N-IBDQ**	185 (179-196)	172 (166-178)

Estimated marginal mean scores adjusted for age and education. PF physical function, RP role physical, BP body pain, GH general health, VT vitality, SF social function, RE role emotional, MH mental health. *p < 0.05, **p < 0.01, ***p < 0.001. (95%CI) 95% confidence intervals.

Conclusion: In this population-based IBD cohort HRQoL measured 20 years after diagnosis was in general comparable to the reference population. However, HRQoL in female IBD patients was lower than in males. Independent factors associated with reduced HRQoL were: CRP > 5, current symptoms and not working in CD, SCCAI > 2.5 and chronic fatigue in UC.

Disclosure of Interest: None declared

P0931 OVERVIEW OF HEPATITIS B IMMUNIZATION PRACTICE AND VACCINATION RESPONSE IN GREEK INFLAMMATORY BOWEL DISEASE PATIENTS

D. Calogera¹, E. Zambeli², E. Tsironi³, M. Tzouvala⁴, A. Kostas¹, E. Kourkoutas², S. I. Siakavellas¹, K. Filippakou³, D. Moschovis⁴, J. Vlachogiannakos¹, S. Michopoulos², G. Papatheodoridis¹, G. Bamias¹

¹Academic Department of Gastroenterology, Kapodistrian University of Athens, Laikon Hospital, ²Gastroenterology Department, Alexandra General Hospital, Athens, ³Gastroenterology Department, Metaxa Memorial Cancer Hospital, ⁴Gastroenterology Department, St. Panteleimon Nikaia General Hospital, Piraeus, Greece

Contact E-mail Address: gbamias@gmail.com

Introduction: Low vaccination rates against hepatitis B virus (HBV) have been reported in patients with IBD, as well as sub-optimal responses to vaccination. ECCO has currently advised for vaccination of non-immune IBD patients with an aim of achieving levels of anti-HBs > 100 IU/l for adequate seroprotection, in particular when immunosuppressive therapy is planned. The appropriate management in this setting remains to be fully specified.

Aims & Methods: We have initiated a multi-centre study in the metropolitan area of Athens, Greece, to evaluate a) the percentage of Greek IBD patients with protective anti-HBs levels; b) the response to vaccination; and, c) the effect of various patient and disease-related parameters on the efficacy of vaccination.

We reviewed the clinical records of all IBD patients with a regular follow-up at 4 tertiary hospitals at the Athens Metropolitan area. All patients were tested for HBsAg, anti-HBs and anti-HBc antibodies. Patients younger than 65-y-old with negative tests for both HBsAg and anti-HBc were managed as follows: a) negative anti-HBs without/unknown history of vaccination: 3-dose vaccination (0, 1, 6 mo) with 20 μg, b) history of vaccination: anti-HBs levels >100iu/l: annual follow-up of anti-HBs levels; anti-HBs 10-100iu/l, 1-3 20 μg doses with anti-HBs measurement after each dose; no anti-HBs, 1-3 40 μg doses with anti-HBs measurement after each dose. Vaccination was considered complete when anti-HBs > 100iu/l were detected. In patients with negative anti-HBs levels after 3x20 μg doses, vaccination was repeated with a double dose (40 μg) with anti-HBs measurement after each dose.

Results: We have included 446 IBD patients so far in our study (CD=267, UC=176, IC=3, male=226, age: 42.2 ± 15.3, 16-89). Among 328 patients with recent HBV serology, there were 5 with chronic HBV infection (HBsAg+) and 29 patients with previous exposure to HBV (HBsAg-, anti-HBc+). Protective immunity due to previous vaccination (HBsAg-, anti-HBc-, anti-HBs+>100iu/L) was detected in 23.8% (n=78). Sub-optimal anti-HBs levels were seen in 10.1% (n=33). The majority of tested patients were negative for all three markers (HBsAg, anti-HBc, and anti-HBs), indicating lack of effective vaccination (n=183, 55.8%). If only patients less than 65-y-old were analyzed (n=280), effective immunity was still absent in 54.3%. There was significant association (p < 0.001) between age and presence of protective immunity that is probably due to the widespread application of HB vaccination at early ages in the last 2 decades in Greece. Vaccination was commenced in 125 patients so far, with 64 having finished their regimen. Response has been assessed in 31 patients with 18 (58.1%) achieving sufficient response and 13 requiring double dose vaccination.

Conclusion: A significant percentage of Greek IBD patients lack protective immunity against HBV. The “classical” vaccination regimen often fails to induce adequate levels of anti-HBs antibodies. Increased awareness, intensified vaccination protocols and frequent testing of response may be required in this population.

Disclosure of Interest: None declared

P0932 EXPRESSION OF INTESTINAL ALKALINE PHOSPHATASE (IAP) IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

S.-Y. Park¹, J.-Y. Kim¹, S.-M. Lee¹, H.-S. Kim¹, C.-H. Park¹, S.-K. Choi¹, J.-S. Rew¹

¹Chonam National University Hospital, Gwangju, Republic of Korea

Contact E-mail Address: drpsy@naver.com

Introduction: Intestinal alkaline phosphatase (iAP) functions as a gut mucosal defense factor by detoxifying pro-inflammatory bacterial and endogenous components. The aim of this study was to compare the expression of iAP in inflamed colon mucosa to that in non-inflamed colon mucosa of inflammatory bowel disease (IBD) patients.

Aims & Methods: Colon mucosal specimens were obtained from IBD [18 with ulcerative colitis (UC), 17 with Crohn’s disease (CD)] during colonoscopy. iAP from each specimen was quantified using ELISA. The expression levels of profinflammatory cytokins in IBD patients were determined by real-time polymerase chain reaction. The activation of iAP in cells treated with enteropathogenic Escherichia coli (EPEC) was determined by Western blo

Results: A total of 35 consecutive patients (18 UC, 17 CD) were included in this study. In IBD patients, the protein level of iAP in inflamed mucosa was significantly (average fold: 2.34; p < 0.001) higher than that in non-inflamed mucosa. The mRNA levels of inflammatory genes IL-6, TNF-α and TLR-4 in inflamed mucosa were significantly higher than those in non-inflamed mucosa (p < 0.05). There was significant correlation between endogenous iap and CDAI in CD patients (p = 0.038, r = 0.506). In EPEC-treated epithelial cells, the protein levels of iAP were significantly higher than that in cells not treated by EPEC (p < 0.05).

Conclusion: Endogenous iAP was increased in inflammatory mucosa in IBD patients with protective role against gut inflammation at suboptimal levels. Further study is needed to determine the role of iAP in patients with IBD.

Disclosure of Interest: None declared

P0933 PREVALENCE AND DISEASE COURSE OF INFLAMMATORY BOWEL DISEASE DIAGNOSED IN ASYMPTOMATIC PATIENTS DURING SCREENING COLONOSCOPY

I. Rodriguez - Lago¹, M. Fernández - Calderón², J. Fernández¹, I. Moraleja¹, I. Idígoras³, I. Portillo³, J. L. Cabriada¹, on behalf of IBD Study Group from the Basque – Navarre Society of Gastrointestinal Diseases

¹Gastroenterology Department, Galdakao Hospital, Bilbao, ²Gastroenterology Department, Mondragón–Alto Deba Hospital, Mondragón, ³Colorectal Cancer Screening Programme. Basque Country Health Service, Bilbao, Spain

Contact E-mail Address: iago.r.lago@gmail.com

Introduction: There is sparse evidence about the prevalence of Inflammatory Bowel Disease (IBD) in asymptomatic patients. We have data from retrospective studies in different countries ranging from 0.7 to 1.6%. Interestingly most of the patients developed symptoms related to the disease during the next 5 to 10 years of follow up. We have conducted a study to evaluate the prevalence, disease characteristics and treatment requirements in patients diagnosed of IBD during screening colonoscopy in asymptomatic patients in our area.

Aims & Methods: We have retrospectively reviewed the medical chart of all the patients who underwent a colonoscopy under the colon cancer screening programme in the Basque Country (Spain). This study was designed and conducted in two hospitals from the IBD Study Group from the Basque – Navarre Society of Gastrointestinal Diseases. The screening in our area started in 2009 and it covers people between 50 and 69 years from a population of 2.2 million people. All patients were assessed with fecal occult blood test (FOBT) and, if this test was positive, a colonoscopy was performed. The inclusion criteria in the present study included a diagnosis of IBD established by endoscopy and confirmed by histology during the colon cancer screening programme.

Results: A total of 70.299 FOBT were done in our two hospitals. In 4.717 (6.7%) of these cases a colonoscopy was performed. We have found 14 patients (0.3%) diagnosis of IBD: Ten cases of ulcerative colitis (UC), two of Crohn’s disease (CD) and two of indeterminate colitis. Nine of them are women, and most of them have never smoked. The median age at diagnosis was 55 years [51.5-60]. UC extension was classified as E1 in 3 patients, in 4 as E2 and in 3 as E3. All four patients with CD and IBD unclassified suffered only colonic involvement. Endoscopic activity was scored as UCEIS 5 [4-5.5]. Only one patient suffered perianal disease and extraintestinal manifestations, both at diagnosis. Median follow-up time since the diagnosis was 12 months [8.5-29.5]. Five patients (35%) developed symptoms during this period (rectal symptoms/ diarrhoea/ rectal bleeding). Treatment was indicated with mesalazine in 11 cases, steroids in 3 and 2 with azathioprine. No patients required methotrexate or biologics. Only one patient required surgery because of a mass in transverse colon at diagnosis to rule out an underlying cancer.

Conclusion: We have found a 0.3% prevalence of IBD during screening colonoscopies in our area. All cases had exclusive colonic involvement. After a medium – term follow – up the disease behaviour is relatively mild. Our preliminary data need to be explored in future studies with a greater number of patients and a longer – follow up.

Disclosure of Interest: None declared

P0934 CLINICAL INEFFICACY OF GOLIMUMAB IN ULCERATIVE COLITIS PATIENTS IS INDEPENDENT OF IMMUNOGENICITY

I. Detrez¹, A. de Vries², E. Brouwers¹, G. Van Assche³, S. Vermeire³, M. Ferrante³, A. Gils¹

¹KU Leuven, Leuven, Belgium, ²Sanquin, Amsterdam, Netherlands, ³University Hospitals Leuven, Leuven, Belgium

Introduction: Golimumab (GOM, Simponi®), a therapeutic antibody targeting tumor necrosis factor (TNF) alpha, has recently been approved for treatment of moderate to severe Ulcerative Colitis (UC). The PURSUIT-SC induction study showed that 51.0% of patients responded clinically upon sub-cutaneous administration of GOM 200/100 mg at weeks 0 and 2.

Aims & Methods: (1) To develop monoclonal antibody (MA)-based immunoassays for the determination of GOM and anti-GOM concentrations (2) To evaluate the clinical significance of these assays in a small cohort of 15 UC patients receiving GOM maintenance dosing (50 mg or 100 mg) after induction of therapy. For the quantification of GOM serum concentrations, both a MA-based TNF-coated ELISA and a MA/MA-based sandwich-type ELISA were developed. Assay performance was assessed using 64 patient serum samples. External analytical validation was performed through collaboration with Sanquin. For quantification of the anti-GOM antibody response, a bridging ELISA was developed and samples were analyzed neat and after an acid-treatment step. Clinical response and C-reactive protein (CRP) were determined.

Results: Analyzing 64 serum concentrations of GOM-treated UC patients revealed an excellent correlation between the two immunoassays: Spearman’s rho 0.981, p < 0.0001; intra-class correlation coefficient (ICC) of 0.972. The sandwich-type ELISA demonstrated higher sensitivity and specificity as compared to the TNF-coated ELISA and is therefore our preferred assay. External validation of the sandwich-type ELISA using 20 patient serum concentrations showed a good Pearson's r (0.969, p < 0.0001) and ICC (0.926). Treatment of seven out of 15 UC patients was terminated within 14 weeks due to inefficacy. However, in all serum samples tested, anti-GOM levels were <3.2 ng/mL even when an acid dissociation step was included to dissociate the GOM/anti-GOM complexes. Comparing consecutive GOM levels of a representative responder versus a representative non-responder revealed significantly different pharmacokinetics, which were also reflected in the clinical and biochemical response parameters of these patients (Table 1).

Abstract number: P0934 Table 1.

Clinical, biological and biochemical characteristics of a typical responder and non-responder

	responder					non-responder
Week	Dose (mg)	TC (µg/mL)	ATG (ng/mL)	Partial Mayo	CRP (mg/L)	Dose (mg)	TC (µg/mL)	ATG (ng/mL)	Partial Mayo	CRP (mg/L)
W0	200	<0.1	<3.2	6	8.7	200	ND	<3.2	8	8.0
W1		9.8	<3.2				9.9	<3.2
W2	100	10.4	<3.2	ND	4.2	100	4.6	<3.2	8	4.0
W4		14.9	<3.2				3.8	<3.2
W6	50	8.4	<3.2	2	5.4	50	1.5	<3.2	6	4.6
W14	50	6.2	<3.2	0	4.8	0	1.0	<3.2	ND	16.6

TC, Trough concentration;ATG, antibodies towards GOM;CRP, C-reactive protein;ND, not determined

Conclusion: In this study, highly sensitive MA-based immunoassays were developed for the specific quantification of serum GOM and anti-GOM concentrations and applied on a cohort of 15 UC patients. Despite major differences in pharmacokinetics between responders and non-responders, no antibodies against GOM were detected. Based on these preliminary results, we hypothesize that efficacy could be improved by higher or more frequent GOM doses for patients with inadequate treatment responses or by increasing GOM absorption.

Disclosure of Interest: I. Detrez: None declared, A. de Vries: None declared, E. Brouwers: None declared, G. Van Assche Financial support for research: MSD, Abbvie, Lecture fee(s): MSD, Abbvie, Takeda, Ferring, Consultancy: MSD, Abbvie, Takeda, Ferring, Genetech/Roch, Pfizer, S. Vermeire Financial support for research: MSD, Abbvie, Lecture fee(s): MSD, Abbvie, Takeda, Falk, Tillotts, Consultancy: MSD, Abbvie, Takeda, Falk, Ferring, Shire, Galapagos, Hospira, Mundipharma, Genetech/Roch, Pfizer, Celgene, M. Ferrante Financial support for research: Takeda, Lecture fee(s): Abbvie, Janssen, MSD, Chiesi, Tillots, Zeira, Consultancy: Abbvie, Janssen, MSD, Boehringer-Ingelheim, Ferring, A. Gils Lecture fee(s): MSD, Janssen Biologicals

P0935 PRESENCE OF LIVER TEST ABNORMALITIES AT DIAGNOSIS IS ASSOCIATED WITH OCCURENCE OF COMPLICATED DISEASE BEHAVIOR IN PATIENTS WITH CROHN'S DISEASE

J. Maljaars¹, J. Barendregt¹, M. de Jong¹, B. van Hoek¹, R. Veenendaal¹, A. van der Meulen¹, N. Srivastava², R. Stuyt³

¹Dept.of Gastroenterology-Hepatology, Leiden University Medical Centre, Leiden, ²Dept.of Gastroenterology-Hepatology, Medical Centre Haaglanden, ³Dept.of Gastroenterology-Hepatology, Haga Hospital, The Hague, Netherlands

Contact E-mail Address: p.w.j.maljaars@lumc.nl

Introduction: In patients with Crohn's disease, liver test abnormalities (LTA) are a frequent phenomenon. Although clinical experience may suggest a relationship between disease severity and presence of LTA, this has not been extensively studied. In celiac disease, presence of LTA has been associated with the degree of mucosal damage. In Crohn's disease, the degree of mucosal damage is associated with a poor prognosis. In this study, we aim to investigate whether the presence of LTA is associated with a poor prognosis in newly diagnosed Crohn's disease patients.

Aims & Methods: We performed a retrospective cohort study in all patients diagnosed between 2004 and 2011 in a tertiary IBD centre and 2 large teaching hospitals. All new cases of Crohn's disease were included in the study when liver test results from before the start of treatment were available. Patients with liver disease, manifest at diagnosis or during follow up, were excluded. Patients were scored for patient characteristics, occurence of complications (such as stenosis or perforation), hospitalizations and surgeries. Liver test abnormalities (LTA) were defined as a value of either alkaline phosphatase (AP), Gamma Glutamyl transferase (GGT), Aspartate Aminotransferase (AST) or Alanine Aminotransferas (ALT) above the upper limit of normal. Complicated behavior at diagnosis was defined as having any form of non-B1 behavior at diagnosis.

Follow-up was ended after 60 months or at the occurence of a complication.

Results: In 383 newly-diagnosed patients with Crohn's disease, LTA were found in 135 patients.

No differences in Montreal classification at diagnosis were found between patients with and without LTA. Patients with LTA more often developed complications compared to patients without LTA (either stenosis or perforation; 33% vs 15% resp., p < 0.001). Using a multivariate analysis, LTA (p < 0.001, Hazard ratio (HR)2.3), complicated behavior at diagnosis (p=0.019, HR 1.7), CRP at diagnosis (p=0.032, HR 1.003) and involvement of the small bowel (p=0.05, HR 1.9) were associated with the occurence of a new stenosis or perforation.

During the 5 year follow-up period, 54% of patients with LTA were hospitalized, compared to 35% of non-LTA patients (p=0.001). Using a multivariate analysis, both presence of LTA at diagnosis (p=0.005, HR 1.56) and complicated behavior at diagnosis (p=0.003, HR 1.5) were associated with an increased risk for hospitalization.

Eighty out of 135 patients with LTA had an increased AP, and 27 of these 80 patients developed complicated disease behavior compared to 54 out of the 303 patients without LTA (33% vs. 15%, p=0.003). Out of the 80 patients with an increased AP, 44 were hospitalized during the 5 years follow up compared to 117 of 303 patients with normal AP (55% vs 38%, p=0.011).

Conclusion: In this study we have demonstrated that presence of LTA at diagnosis is associated with a poor prognosis, as both the risk for developing a new complication or the need for hospitalization were higher in the LTA-group. Presence of an increased AP at diagnosis has the highest predictive value.

Disclosure of Interest: None declared

P0936 NORMALIZED HS-CRP AND EARLY MUCOSAL HEALING AFTER INDUCTION CAN PREDICT SUSTAINED RESPONSE IN PATIENTS WITH CROHN`S DISEASE AFTER ONE YEAR INFLIXIMAB THERAPY

J. Tang¹, X. Gao¹, M. Zhi¹, P. Hu¹

¹Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, GuangZhou, China

Contact E-mail Address: tangjiansys@163.com

Introduction: High sensitive C-reactive protein (hs-CRP) and early mucosal healing are thought to be usefulin monitoring disease activity during infliximab therapy, but how to combine these two index to be a more useful tool to predict sustained response remains unclear. We aimed to investigate the predict value of hs-CRP combined with early mucosal healing in patients undergoing infliximab therapy.

Aims & Methods: 76 patients were retrospectively enrolled after initiating infliximab therapy in our center. All patients responded to infliximab after induction had been scheduled for every 8 weeks shooting. Hs-CRP was tested at 14wks after induction. Normalized hs-CRP was defined as hs-CRP=0-3mg/L. Endoscopic examinations were carried out at 14wks and 52wks. Mucosal healing was defined as no ulcer or only scar.

Results: Hs-CRP was normalized in 57%(44/76) of all patients. Patients with normalized hs-CRP had higher mucosal healing rate and lower loss response rate than the other group at 52wks (53%vs37.50%, P=0.04; 15%vs40%, P=0.02). 55% (42/76) of all patients reached mucosal healing at 14 wks. Patients with early mucosal healing also had higher mucosal healing rates and lower loss of response rate at 52wks (64%vs17%, P<0.01; 17%vs42%, P=0.04). Normalized hs-CRP combined with early mucosal healing had significant value in predicting sustained response and mucosal healing at 52wks. 70% (21/30)patients with normalized hs-CRP and early mucosal healing reached mucosal healing and 93% (28/30) of them maintained a sustained response to infliximab at 52wks.

Conclusion: Normalized hs-CRP and early mucosal healing after induction can effectively predict mucosal healing andsustained response in patients undergoing infliximab therapy.

Disclosure of Interest: None declared

P0937 POST-INDUCTION SERUM INFLIXIMAB TROUGH LEVEL AND ANTIBODYARE ASSOCIATED WITH ONE YEAR OUTCOME AFTER INITIATING THERAPY IN CROHN`S DISEASE

J. Tang¹, X. Gao¹, M. Zhi¹, P. Hu¹

¹Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, GuangZhou, China

Contact E-mail Address: tangjiansys@163.com

Introduction: Serum infliximab trough level(S-IFX) and antibody were documented to correlate with sustained infliximab response. Aim of this study was to identify relationship between trough levels, antibodies and clinical outcome in a cohort on maintenance infliximab therapy.

Aims & Methods: 64 patients were retrospectively enrolled. All received a scheduled maintenance therapy after response to infliximab induction. S-IFX and antibodies were tested in at 14 weeks after initiating treatment. Rate of loss response and endoscopic activity were evaluated at 52weeks.

Results: At week14, S-IFX was 5.28 ± 7.24ug/ml and 23%(15/64) of all patients developed antibodies. S-IFX was significantly lower in patients with antibody (2.91 ± 5.40ug/ml vs 6.00 ± 7.61ug/ml, P=0.02). During 52 weeks follow up, 28% (18/64) patients lost of response to infliximab. The patients who lost of response had lower S-IFX than patients had sustained response (2.16 ± 3.05ug/ml vs 6.50 ± 8.02ug/ml, P=0.03) while no significant difference was found on drug antibodies (38% vs 22%, X=2.50, P=0.11). At week 52, 62 patients had undergone ileo-colonoscopy and 30 patients reached mucosal healing. Mucosal healing group had relatively higher S-IFX than who did not reach mucosal healing (8.11 ± 9.33ug/ml vs 2.56 ± 2.90ug/ml, P<0.01) but no statistical difference for antibodies between these two groups (17% vs 28%, P=0.28). S-IFX had a predictive value on sustained response and mucosal healing in 52 weeks follow up. When S-IFX > 2ug/ml, the sensitivity for predicting sustained response and mucosal healing were76% and 83%, the specificity were 72% and 56% ( AUC=0.76, P<0.01;AUC=0.78, P<0.01). Baseline albumin level and BMI were 41.44 ± 6.95g/l and 21.45 ± 3.56 in sustained remission patients. S-IFX was correlated to albumin level and BMI (r=-0.79, P<0.01;r=-0.46, P<0.01).

Conclusion: Post-induction serum IFX trough level could predict sustained response and mucosal healing in CD patients undergoing IFX treatment. Nutritional status before treatment was correlated to serum IFX trough level.

Disclosure of Interest: None declared

P0939 EARLY POST-OPERATIVE ENDOSCOPIC EVALUATION AFTER ILEOCECAL RESECTION IN CROHN’S DISEASE REDUCES CLINICAL RECURRENCE

J. Carvalho, E. Branco¹, A. Oliveira¹, L. Lourenço¹, M. Cardoso¹, V. Anapaz¹, C. G. Rodrigues¹, L. Santos¹, S. F. Alberto¹, A. Martins¹, J. Reis¹, J. R. Deus¹

¹Gastroenterology, Hospital Professor Doutor Fernando da Fonseca, Lisbon, Portugal

Contact E-mail Address: cbranco.joana@gmail.com

Introduction: In Crohn’s disease, the recurrence rate after ileocecal resection is high, around 20-25% per year without therapy^1,2, and is best predicted by endoscopy rather than clinical indeces¹. Since 2010, the European Crohn’s and Colitis Organization guidelines recommends performing ileocolonoscopy 6 to 12 months after surgery to predict clinical behavior³, which has therapeutic implications.

Aims & Methods: The aim of this study is to evaluate the impact of this endoscopic evaluation on early post-operative clinical recurrence.

This is a retrospective analysis of a cohort of Crohn’s disease patients submitted to ileocecal resection at our Hospital with updated follow-up until 2014. Patients were distributed into two groups, whether they had or not performed ileocolononoscopy within 12 months after surgery, group P or NP respectively. We evaluated different levels of reccurence: clinical, defined as symptomatic disease needing corticotherapy or an escalating immunossupresive regimen; endoscopic, defined by Rutgeert’s endoscopic score; and surgical, defined as necessity of surgical reintervention.

Results: We included 66 patients, of whom 34 (51.5%) women, with an average age at diagnosis of 34.5 ± 13.6 years, average age at surgery of 37.1 ± 13.7 years, median follow-up time after surgery of 152 ± 120 months; 35 (53%) with penetrating disease and 10 (15.2%) with perianal disease. Previous to surgery, 9 (13.6%) patients were on immunosupressive therapy, 4 (6%) of them on combined therapy. All patients have undergone post-operative prophylaxis with messalazine, in 16 (24.2%) of them azathioprine was added and in 4 (6%) biologic therapy was started. There were 27 (41%) patients on group P and 39 (59.1%) on group NP. We have found endoscopic reccurence in 46 (69%), clinical reccurence in 35 (53%) and surgical reccurence in 8(12.1%). Patients on group P had less clinical reccurence than group NP (66.6% vs. 33%; p=0.01).

Conclusion: Early endoscopic evaluation after ileocecal resection in Crohn’s disease has a positive impact on clinical evaluation as this group of patients shows less clinical reccurence than patients that are not systematically submitted to this evaluation and this is in accordance to previous published data⁴.

Disclosure of Interest: None declared

P0940 COMPARISON MR ENTEROGRAPHY AND COLONOSCOPY IN DETECTING FINDINGS OF INFLAMMATORY BOWEL DISEASE IN CHILDREN

J. Sieczkowska¹, B. Marcinska², M. Dadalski¹, D. Jarzebicka¹, J. Kierkus¹, E. Jurkiewicz²

¹Department of Gastroenterology, Hepatology, Nutrition and Pediatrics, ²Department of Diagnostic Imaging, The Children’s Memorial Health Institute, Warsaw, Poland

Contact E-mail Address: joannasieczkowska@wp.pl

Introduction: Diagnostic process for Inflammatory bowel disease (IBD) based on magnetic resonance of small bowel and endoscopy. Magnetic resonance is considered as the first-line imaging modality because of high efficacy for detecting IBD findings and lack of ionizing radiation. Before colonoscopy bowel cleansing is necessary. It is often problematic and bad tolerated by young patients. Specially in children the procedure of general anesthesia is needed.

Aims & Methods: The aim of this study was to compare detecting findings of disease by colonoscopy with MR-enterography proceeded for small bowel assessment. We tried to asses utility of MR-enterography in detecting lesions in the colon.

A retrospective assessment of 59 children with suspected or diagnosed IBD was done. All of the patients underwent colonoscopy and MR-enterography for small bowel disease localization within no longer than 23 weeks (only 1 patient had gap between studies 41 weeks). Localization of disease was described in 7 segments of the end part of small and large bowel: terminal ileum, cecum, ascending colon, transverse colon, descending colon, sigmoid colon, rectum. During MR procedure was assessed wall thickening bowel wall enhancement and presence lesions after DWI.

Results: The most common localization of findings of disease viewed by colonoscopy was ileum (88%). In rectum disease was in 56% of patients. The sensitivity and specificity for detecting lesions in the rectum bowel wall enhancement was in 42.3% and 96.7%, DWI 32% and 93.6%, wall thickening 26.9% and 96.7%; sigmoid colon 45.5% and 97.1%, DWI 40.9% and 88.6%, wall thickening 36.4% and 97.1%; descending colon 41.2% and 97.5%, DWI 29.4% and 95%, wall thickening 41.2% and 97.5%; transverse colon 50% and 100%; 43.8% and 100% for DWI and 43.8% and 100% for wall thickening; ascending colon 53.3% and 95.4%; DWI 46.7% and 95.4%, wall thickening 53.3% and 100%; cecum 57.1% and 93.1%, 50% and 93.2% for DWI, 50% and 97.7% for wall thickening; terminal ileum 53.9% and 79.6%, 61.5% and 77.3%, 61.5% and 77.3% respectively.

Conclusion: MRI characterized very high specificity in detecting disease lesion in colon. Unfortunately sensitivity wasn’t enough high. Lack of IBD findings in MR does not exclude presence of disease. The sensitivity was better in higher segments of the bowel, what can suggest that additional rectal contrast may be obligatory for better detection of lesions in lower part of the colon.

Disclosure of Interest: None declared

P0941 ROUTINE COLONOSOPIC BIOPSIES – SHOULD PRACTICE CHANGE?

J. Easaw¹, A. Bennett¹, F. Leslie¹, A. Ramakrishnan¹

¹Gastroenterology, University Hospital of North Midlands Nhs Trust, Newcastle Under Lyme, United Kingdom

Contact E-mail Address: arulraas@yahoo.com

Introduction: American society for gastrointestinal endoscopy¹ (ASGE) and Joint advisory group on Gastointestinal endoscopy (JAG) suggest routine colonic biopsies as quality indicator and auditing our practice to identify microscopic colitis. UK studies suggest low incidence of microscopic colitis² and additional costs making one wonder whether we should be doing this routinely and/or auditing our practice?

Aims & Methods: We perfomed a retrospective database search of colonoscopy requests from July-December 2013 with keywords diarrhoea, loose stools & change in bowel habits to audit our practice as a quality indicator as per ASGE and JAG. Demographics, endoscopic findings & histology were collected from electronic records.

Results: From the 1124 requests, 407 colonoscopies were performed with the indication for diarrhoea, loose stools or change in bowel habit. Colonic biopsies were taken in 325 cases (79.9%) and right sided biopsies were specifically taken in 279 cases (68.6%). 60% of our colonoscopies were reported as macroscopically normal (241/407) and only 5.2% (17/325 colonoscopy biopsies) cases of microscopic colitis were picked up on routine biopsies. Among diagnosed with microscopic colitis, the mean age was 60.1 years (range 38-80, 76% > 50 years) with a female to male ratio of 14:3. Micropsopic colitis was diagnosed at an average biopsy cost of £1545 (total £26,266 spent on biopsies to identify 17 patients, not factoring colonoscopy tariffs or endoscopist/histopathologist time).

Conclusion: Our rate of routine colonoscopic biopsies in patients with diarrhoea³ and the pickup rate of microscopic colitis⁴ is similar to previous reports. We conclude that one case of microscopic colitis (5.2%) is diagnosed for every 20 colonoscopy perfomed for diarrhoea at a biopsy cost of £1545; age/sex may help in increasing pickup rate and to decrease routine biopsy rates.

Disclosure of Interest: None declared

P0942 COMPARISON OF COMMERCIALLY AVAILABLE ASSAYS FOR INFLIXIMAB CONCENTRATIONS AND ANTIBODIES TO INFLIXIMAB WITH ASSAYS DEVELOPED AT JANSSEN AND USED IN CLINICAL STUDIES OF REMICADE® (INFLIXIMAB) IN IBD PATIENTS

J. Marini¹, J. Sendecki², F. Cornillie³, J. Popp⁴, M. Blank⁴, S. Black⁴, K. Chun⁵, A. Gils⁶, T. Van Stappen⁶, L. Therien⁷, D. Hamann⁸, T. Rispens⁸, G. Shankar⁹

¹Janssen R&D, LLC, ²Janssen R&D, LLC, Spring House, United States, ³Immunology, MSD International, Lucerne, Switzerland, ⁴Immunology, Janssen Scientific Affairs, LLC, Horsham, ⁵Immunology, LabCorp, Burlington, United States, ⁶Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium, ⁷Operations GD Specialized Diagnostics, Dynacare, Montreal, Canada, ⁸Immunopathology, Sanquin, Amsterdam, Netherlands, ⁹Immunology, Janssen R & D, LLC, Spring House, United States

Contact E-mail Address: GShanka3@its.jnj.com

Introduction: Infliximab(IFX) concentrations and antibodies to IFX(ATI) titers can be informative in assessing IBD response.

Aims & Methods: In collaboration with KU Leuven(Belgium), Sanquin(The Netherlands), Dynacare(Canada) and LabCorp(USA), the accuracy and reliability of commercially available IFX and ATI assays were compared to assays used by Janssen for Remicade®(IFX) IBD studies. Test samples were prepared by Janssen, blinded and frozen at -70°C and shipped to the labs; blinded analysis was also performed at Janssen. IFX concentration (49 samples) and ATI titer (32 samples) were assessed. KU Leuven* and Dynacare utilized enzyme-linked immunosorbent assay (ELISA) to measure IFX and ATI. Sanquin used ELISA to measure IFX and a radioimmunoassay to measure ATI.LabCorp used electrochemiluminescence immunoassay (ECLIA) to measure IFX and ATI. Janssen used ELISA for IFX quantification, and ELISA (“old”) and ECLIA (“new”) for ATI assessments.

Results: IFX Assays: Specificity:All assays were specific as they detected IFX alone, but not 5µg/mL of adalimumab, certolizumab pegol, golimumab or siltuximab. Selectivity: TNFα (0.5 – 50 ng/mL) did not interfere with IFX detection in any assays, whereas the presence of ATI titers >10 interfered with IFX assessment in all assays. Accuracy: Accuracy was confirmed by 3 independent measurements of IFX (0.125-20µg/mL) spiked sera from untreated IBD patients and with IFX measured in sera from IFX-treated IBD patients. Precision: All IFX assays were precise as determined by inter-occasion reproducibility (2wks between assays of IFX-spiked IBD sera; Dynacare assessed the samples the same day). Pearson R values describing the correlation of Janssen IFX results to IFX results from Sanquin, Dynacare, KU Leuven, and LabCorp were 0.936, 0.945, 0.968 and 0.972, respectively.

ATI assays: Specificity: Assays from all labs and Janssen were specific in detecting anti-IFX antibodies; results were not affected by high titers of antibodies against other human monoclonal antibody drugs (ustekinumab and golimumab). Selectivity: The Sanquin, LabCorp and new Janssen methods were drug tolerant (IFX >10ug/mL); ATI results from Dynacare and KU Leuven were affected by IFX concentrations at 2ug/mL or higher. Concentrations of free or bound TNFα (<5ng/mL) did not interfere with ATI detection; but a high (supraphysiologic) TNFα concentration (50ng/mL) resulted in false positive results in all assays except Sanquin’s. Precision: All ATI assays were reproducible (2wks between assays of human sera containing ATI; Dynacare assessed samples the same day).

Conclusion: Results from KU Leuven, Sanquin, Dynacare and LabCorp were similar and significantly correlated to the results of Janssen assays. These results may aid in interpretation of data from commercial assays and assays used in IBD clinical studies of Remicade®(IFX).

*assay distributed by apDia and R-biopharm

Disclosure of Interest: J. Marini Conflict with: Employee Janssen R & D, LLC, J. Sendecki Conflict with: Employee Janssen R & D, LLC, F. Cornillie Financial support for research: Janssen R & D, LLC, J. Popp Conflict with: Employee Janssen Scientific Affairs, LLC, M. Blank Conflict with: Employee Janssen Scientific Affairs, LLC, S. Black Conflict with: Employee Janssen Scientific Affairs, LLC, K. Chun Financial support for research: Janssen R & D, LLC, A. Gils Financial support for research: Janssen R & D, LLC, T. Van Stappen Financial support for research: Janssen R & D, LLC, L. Therien Financial support for research: Janssen R & D, LLC, D. Hamann Financial support for research: Janssen R & D, LLC, T. Rispens Financial support for research: Janssen R & D, LLC, G. Shankar Conflict with: Employee Janssen R & D, LLC

P0943 PERFORMANCE OF FECAL LACTOFERRIN, CALPROTECTIN, PMN-ELASTASIS AND CRP AND WBC COMPARED TO HISTOLOGICALLY DEFINED HEALING IN ULCERATIVE COLITIS

J. Langhorst¹, A. Rueffer², G. Dobos³, J. Boone⁴

¹Chair for Integrative Medicine, University of Duisburg-Essen, Integrative Gastroenterology, Kliniken Essen-Mitte, Essen, ²Enterosan, Labor L + S, Bad Bocklet-Grossenbrach, ³Chair for Integrative Medicine, University of Duisburg-Essen, Internal and Integrative Medicine, Essen, Germany, ⁴Techlab, Blacksburg, Virginia, United States

Contact E-mail Address: j.langhorst@kliniken-essen-mitte.de

Introduction: Microscopic, histological healing may be a better predictor than the macroscopic appearance or clinical criteria for course of disease in ulcerative colitis (UC). Histological assessment revealed that indicators of acute mucosal inflammation, including crypt abscesses, mucin depletion or an acute inflammatory cell infiltrate were associated with a 2-3fold increase in the risk of UC relapse during 12 months’ follow-up. Fecal inflammation biomarkers are increasingly popular because they are noninvasive and individual patients can serve as their own control. However an evaluation of a panel of biomarkers in their performance compared to a histological assessment in UC is lacking.

Aims & Methods: Three sigmoidal and rectal biopsies each were taken randomly or at the site of macroscopic active inflammation for histopathological work-up. Riley score (each category 0-3pts) was performed for signs of acute inflammation including acute inflammatory cell infiltrate, crypt abscesses, mucin depletion and breaches in the surface epithelium. The 4 categories were combined as acute HistoScore with a score=0 indicating histologically defined healing and a score > 0 indicating acute inflammation. In addition, chronic inflammatory cell infiltrate and architectural irregularities were added and combined as HistoSumScore. The 3 fecal biomarker Lactoferrin (LF; >7.25µg/g), Calprotectin (Cal; >50µg/g), PMN-elastasis (PMN-e; >0.062µg/g) as well as CRP (≥0.5mg/dl) and WBC (>8500/µl) were correlated to the HistoSumScore and median (inactive/active), sensitivity, specificity, PPV, NPV and diagnostic accuracy were calculated based on the acute HistoScore.

Results: In 150 UC patients (79 female; age 18-75 years) 238 endoscopic procedures (75 colonoscopies; 163 sigmoidoscopies) were performed. Correlation (Spearman) with the complete HistoSumScore was LF cc=.408; p < 0.0001; PMN-e cc=.447; p < 0.0001; CAL cc=.458; p < 0.0001; CRP cc=.307; p < 0.0001; WBC cc=.203; p=0.002. Comparison to the acute HistoScore showed the following results: LF: median (inactive/active): 3.9/36.5µg/g; sensitivity 71.2%; specificity 64.7%; PPV 71.2%; NPV 64.7%; diagostic accuracy: 68%; optimized cut-off: 10.2µg/g; CAL: median: 10.7/25.7µg/g; sens 27.2%; spec 96.1%; PPV 89.5%; NPV 51.9% diag acc: 58%; opt. cut-off: 16.6µg/g; PMN-e: median: 0.02/0.05; sens 38.2%; spec 84.0%; PPV 72.4%; NPV 55.3%; diag acc: 60%; opt. cut-off: 0.033µg/g; CRP: median: 0.1/0.4mg/dl; sens 43.3%; spec 85.3%; PPV 78.6%; NPV 54.7%; diag acc: 62%; opt. cut-off: 0.25mg/dl; WBC: median: 6500/6750; sens 23.2%; spec 90.3%; ppv 75.0%; npv 48.4%; diag acc: 53%; opt. cut-off: 6620.

Conclusion: The fecal biomarker show sufficient correlation and diagnostic accuracy outperforming CRP and WBC when compared to histology. Only fecal Lactoferrin shows median above the predefined cut-off in histologically active inflammation.

Disclosure of Interest: J. Langhorst Financial support for research: Repha, Falk, Steigerwald, Techlab, Lecture fee(s): Repha, Falk, Techlab, A. Rueffer: None declared, G. Dobos: None declared, J. Boone Conflict with: emloyee of Techlab

P0944 ENDOSCOPIC SURVEILLANCE OF COLITIS IN A DISTRICT GENERAL HOSPITAL

J. Greenland¹, B. Javaid¹

¹Bedford Hospital, Bedford, United Kingdom

Contact E-mail Address: julia.c.greenland@gmail.com

Introduction: The British Society of Gastroenterology (BSG) recommends 2-4 biopsies from every 10cm of the colon in patients undergoing colonoscopy for surveillance in patients with inflammatory bowel disease (IBD) (1). The timing of follow-up surveillance colonoscopies should be based on the risk group determined in part by macroscopic findings.

Aims & Methods: 1. To establish compliance with BSG Guidelines for IBD endoscopic surveillance in a district general hospital. 2. To conduct a questionnaire regarding IBD surveillance to direct an improvement in the service.

All endoscopy reports between 1999 and January 2015 coded as “IBD surveillance” were reviewed. The total number of biopsies taken in each procedure and the number of individual sites biopsied throughout the colon was recorded. This was compared to a target of a minimum of 2 biopsies at 6 sites (total of 12 biopsies). The number of colonoscopies which met this target was recorded.

Secondly, the endoscopy report was reviewed. The patients were separated into low, intermediate and high-risk groups according to the macroscopic findings. The time until their next surveillance endoscopy was recorded and compared to the BSG guidelines for each risk group.

Once the results of the above analysis were established, a questionnaire was designed to explore the reasons behind any failings in the service by asking endoscopists a number of questions.

Results: A total of 278 colonoscopies involving 108 patients were reviewed. The mean total number of biopsies taken was 11.05, and the mean number of sites biopsied was 3.28. Out of the colonoscopies reviewed, 46 out of 278 (17%), met the BSG target for biopsies.

Of the 278 colonoscopies, 55 (20%) were higher risk, 92 (33%) intermediate and 130 (47%) were lower risk. One patient had unknown category. For each colonoscopy, the number of years until the next screening colonoscopy was calculated. This was compared to the BSG target for follow up. 79% met the target year according to risk group. Of note, if the intended date for the next surveillance colonoscopy was after January 2015, the target was said to have been met.

A questionnaire was sent to 12 endoscopists and replies were received from 8. All that replied were aware of the guidelines and agreed with their importance. Time pressure was thought to play a role in failure to meet biopsy targets, with an average score of 2, where a score of 5 indicates that time pressure always plays a role.

There was also a unanimous agreement that a centralised computer database to ensure timely follow up would be beneficial. Other suggestions for service improvement included the use of pan-colonic dye spray, designated surveillance endoscopy lists and a printed version of the protocol on request cards.

Conclusion: Currently our hospital is not meeting the BSG target for IBD surveillance colonoscopies, with a failure to take adequate numbers of biopsies. The opinions of the endoscopists suggest that this is in part due to time pressure, and there could be a role for pan-colonic dye spray, which is not routinely used in our hospital presently.

The hospital is more successful in arranging appropriate follow up colonoscopies. However, there is room for improvement in the service. Feedback suggests that this could be carried out using a computerised database.

Disclosure of Interest: None declared

P0945 QUALITY OF LIFE IN ULCERATIVE COLITIS IS ALREADY IMPAIRED BY MILD DISEASE ACTIVITY

J. Panés¹,*, P. Nos², E. Domènech³, I. Marín-Jimenez⁴, S. Riestra⁵, J. P. Gisbert⁶, X. Calvet⁷, O. Rincón⁸, C. Romero⁸, L. Cea-Calvo⁸, B. Julià⁸ on behalf of Crónica-UC Study Working Group

¹Gastroenterology, Hospital Clinic, Barcelona, ²Gastroenterology, Hospital La Fe, Valencia, ³Gastroenterology, Hospital Germans Trias i Pujol, Barcelona, ⁴Gastroenterology, Hospital Gregorio Marañón, Madrid, ⁵Gastroenterology, Hospital Central de Asturias, Oviedo, ⁶Gastroenterology, Hospital de La Princesa, Madrid, ⁷Gastroenterology, Hospital Parc Tauli, Barcelona, ⁸Medical Dept, MSD, Madrid, Spain

Contact E-mail Address: berta_julia@merck.com

Introduction: The EuroQol (EQ)-5D-5L is a generic instrument measuring health-related quality of life that correlates with disease activity. We have previously described a high agreement between the simple clinical colitis activity index (SCCAI) self-administered by UC patients from home through an online tool with that administered in-clinic by the physician (1). Our aim was to measure which level of disease activity has an impact on QoL in patients with UC.

Aims & Methods: Patients were followed-up for 6 months. At month 3 and 6, they completed the SCCAI at home through a website(CRONICA tool), and thereafter (<48 hours later) the EQ-5D-5L at a visit in which SCCAI was also completed onsite by gastroenterologist, who was blinded to patient’s score. EQ-5D-5L was analyzed as an index value according to the prespecified values for Spanish population with value 1 indicating the best health status and -0.652 the worst. SCCAI scores were analyzed as a continuous variable( from 0 to 19). Spearman’s Rho correlation coefficients were used to assess the correlation between EQ5D-5L and SCCAI measured by patients online and by physician in clinic.

Results: 199 patients (mean age: 39 years [SD 11]; min: 18; max: 67, 55.8% women), contributed with 330 pairs of online completed SCCAI - EQ-5D-5L questionnaires and with 337 pairs of physician SCCAI - EQ-5D-5L questionnaires. The correlation between patients online completed self-administered SCCAI with EQ-5D-5L was moderate (Spearman’s Rho correlation coefficient: 0.49 [p< 0.001]) and similar to that between the SCCAI assessed by the physician in-clinic and the EQ-5D-5L (Spearman’s Rho: 0.53 [p< 0.001]).The correlations between the EQ-5D-5L scores versus the SCCAI scores were all consistent, with a lower SCCAI score corresponding to a higher EQ 5D-5L index, and approximately linear, both when comparing patient online completed SCCAI and SCCAI assessed by the physician in-clinic. (Table 1) An increase on EQ 5D-5L was already observed with a SCCAI of 2, which commonly is considered as remission.Relationship between the EQ-5D-5L and the SCCAI score measured by patients online or by physicians in the clinic.

EQ 5D-5L total
Patient online SCCAI	Mean	SD	Physician in- clinic SCCAI	Mean	SD
0	0.96	0.11	0	0.97	0.05
1	0.95	0.08	1	0.93	0.13
2	0.90	0.09	2	0.88	0.13
3	0.89	0.13	3	0.87	0.14
4	0.87	0.12	4	0.84	0.13
5	0.83	0.15	5	0.83	0.12
6	0.80	0.16	6	0.75	0.17
7	0.85	0.12	7	0.79	0.15
8	0.84	0.23	8	0.56	0.26
9	0.71	0.02	9	0.91	0.01
Total	0.90	0.13	Total	0.90	0.13

Conclusion: In the CRONICA-UC study, QoL measured by the EQ-5D-5L questionnaire is affected proportionally with disease activity. Mild symptoms that are categorized as remission have an impact in QoL. This observation calls for a complete control of all symptoms in patients with UC as a requisite to obtain maximal improvement in QoL.

Disclosure of Interest: None declared

P0946 RETROSPECTIVE EVALUATION OF CLINICAL PRESENTATION OF COLLAGENOUS COLITIS IN JAPAN

K. Yamazaki¹, T. Shinohara², S. Shimizu³, K. Yagi⁴, Y. Hanai⁵, S. Nishiwaki⁶, Y. Fukutomi⁷, H. Araki⁸, M. Shimizu⁸

¹Gastroenterology, Gifu Prefectural General Medical Center, Gifu, ²Gastroenterology, Saku Central Hospital Advanced Care Center, Saku, ³Gastroenterology, JR West Osaka Railway Hospital, Osaka, ⁴Gastroenterology, Niigata Prefectural Yoshida Hospital, Niigata, ⁵Gastroenterology, Chuno Kousei Hospital, Seki, ⁶Gastroenterology, Nishimino Kousei Hospital, ⁷Fukutomi Icyo-Clinic, ⁸Gastroenterology, Gifu University School of Medicine, Gifu, Japan

Contact E-mail Address: kenjiyamayama@yahoo.co.jp

Introduction: Collagenous colitis (CC) often results from the use of proton pump inhibitors (PPIs) in Japan. Non-steroid anti-inflammatory drugs (NSAIDs) or selective serotonin reuptake inhibitors (SSRIs) have also been reported as trigger drugs, but less frequently. Recently, sporadic cases of CC without chronic diarrhea, that were only suspected from endoscopic findings and confirmed by histopathological examination, have been reported.

Aims & Methods: We examined the medication history, endoscopic findings, and clinical features of 93 patients who had been diagnosed with CC at our hospital and joint research institutions.

Results: The mean age of patients was 70.2 years, of which 30 were male and 63 female. Seventy-three patients (78.5%) had a history of PPI treatment. For the remaining 20 patients (21.5%) not administered PPIs, trigger drugs were NSAID in 11, SSRI in 2, and ticlopidine in 1, although a relation of CC to drugs was unknown in 6 patients. Longitudinal ulcers that were characteristic of lansoprazole (LPZ)-induced CC were observed in 20 (29.0%) of 69 patients diagnosed with LPZ-induced CC. An NSAID was concomitantly used in 11 out of these 20 patients. Four patients with longitudinal ulcers had no history of LPZ, including 2 and 1 patient with CC triggered by an NSAID and SSRI, respectively (the trigger drug was unknown in 1 patient). Six patients had no diarrheal symptoms, including 2 with severe abdominal pain and 4 with no symptom of CC. All these 6 patients had longitudinal ulcers detected on endoscopy and were diagnosed with CC on histopathological examination of biopsy specimen.

Conclusion: PPIs are recognized as being the most common trigger drugs for development of CC in the vast majority of patients in Japan. However, this study revealed other drugs to be also involved in about 20% cases. Some patients had CC without chronic diarrhea. In these cases, CC was suspected only from longitudinal ulcers found on endoscopy, which were later confirmed by histopathological examination. Our study suggests that CC is liable to be overlooked in patients who have only minor endoscopic findings or those not investigated by endoscopic examination.

Our study highlights the need for reviewing the clinical protocols and diagnostic criteria for CC, as asymptomatic CC or cases with only acute abdominal pain and no chronic diarrhea, may be overlooked if the existing diagnostic criteria for CC are followed

Disclosure of Interest: None declared

P0947 USE OF POINT OF CARE TRANSABDOMINAL ULTRASOUND TO MONITOR INFLAMMATORY BOWEL DISEASE

K. Novak¹, G. Kaplan¹, S. Ghosh¹, S. Wilson¹², E. Boyce¹, E. Ehtshami Afshar¹, R. Panaccione¹

¹Department of Medicine, ²Department of Radiology, University of Calgary, Calgary, Canada

Contact E-mail Address: knovak@ucalgary.ca

Introduction: Inflammatory bowel disease (IBD) is characterized by periods of disease activity not always reflected by clinical symptoms, interposed with quiescence. Early and appropriate medical intervention aimed to control disease can reduce disease progression and mitigate complications that may result in surgery and hospitalization. Ultrasound (US) is a favorable monitoring strategy, as it is safe, accurate, non-invasive, repeatable and inexpensive. In North America, computed tomography (CT) and magnetic resonance (MR) are preferred imaging modalities to monitor IBD, with limited access to US. Gastroenterologists can accurately perform bedside ultrasound during routine clinic visits for monitoring disease activity and thus facilitate early medical intervention.

Aims & Methods: The aim of this single-centre, prospective study was to evaluate the accuracy of point of care ultrasound (POCUS) performed to detect disease activity in patients with established IBD, relative to gold standard, ileocolonoscopy as well as cross-sectional imaging modalities MR/ MR Enterography, US and CT/CTE. A trained gastroenterologist performed POCUS followed by standard of care monitoring with any of the above modalities, within 3 months. Disease activity was based on presence of increased bowel wall thickness, presence of mesenteric inflammatory fat and lymph nodes, and/or blood flow as seen by color Doppler. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with 95% confidence intervals (CI) were calculated for each comparator modality.

Results: A total of 117 patients were included with 56 (48%) endoscopies, 14 (12%) CT, 34 (29%) US, and 13 (11%) MR completed within 3 months of POCUS examination. The average age was 42.7 years, 72 were female and 45 male. The accuracy of POCUS in detecting disease activity was high, with minimum sensitivity, specificity, PPV and NPV of 88.89%, 81.48%, 83.87%, and 75.0% respectively, found in all comparisons (Table 1).

Abstract number: P0947 Table 1.

Diagnostic accuracy of POCUS compared to Endoscopy, radiologist performed Ultrasound (US), Computed Tomography (CT), and Magnetic Resonance (MR)

	Endoscopy	US	CT	MR
Sensitivity %(CI %)	89.66 (71.50 -97.29)	96.15 (78.42-99.80)	90.91 (57.12-99.52)	88.89 (51.75- 99.72)
Specificity %(CI %)	81.48 (61.25-92.97)	100.00 (59.78-100.00)	100.00 (31.00-100.00)	100.00 (39.76-100.00)
PPV %(CI %)	83.87 (65.53-93.91)	100.00 (83.42-100.00)	100.00 (65.55-100.00)	100.00 (63.06-100.00)
NPV %(CI %)	88.00 (67.66-96.85)	88.89 (50.67-99.42)	75.00 (21.94-98.68)	80.00 (28.36-99.49)

Conclusion: Gastroenterologists can accurately perform bedside US during clinic to detect inflammatory activity in established IBD patients. POCUS may be an effective tool to guide early, goal directed management for these patients.

Disclosure of Interest: None declared

P0948 EARLY AND LATE-ONSET CROHN'S DISEASE: DIFFERENT PHENOTYPE AND COURSE, AN ITALIAN COHORT STUDY

L. Cantoro¹, C. Papi², M. Cicala³, A. Kohn¹

¹Gastroenterology, Azienda Ospedaliera San Camillo-Forlanini, ²Gastroenterology and Hepatology Unit, Azienda Ospedaliera San Filippo Neri, ³Gastroenterology, Campus Bio Medico, Rome, Italy

Contact E-mail Address: laura.cantoro@hotmail.it

Introduction: Disease heterogeneity, according to age of onset, may be observed in Crohn's disease (CD). The prevalence of CD is increasing worldwide. Although the peak incidence is between the second and fourth decade of life, we are observing a significant growth in the number of patients presenting at diagnosis more than 60 or less than 17 years. These ages represent the most critical ones when evaluating the risks and benefits of treatment choices and little is known about their disease history.

Aims & Methods: The aim of the present study was to compare CD phenotype at diagnosis and disease course in diagnosed patients ≤ 17 years (early) and ≥ 60 years (late). Cases included all CD patients diagnosed ≤ 17 years and ≥ 60 years with follow-up > 2 years, recorded in the registry of two IBD referral Centres in Rome. Data reported at diagnosis included gender, smoking habits, IBD family history, IBD location and CD behavior, according to the Montreal classification, extraintestinal manifestations and medical/surgical treatments performed during the follow-up period. Statistical analysis: Chi-squared test, Kaplan-Meier survival method.

Results: Of the entire cohort of 2321 CD, 160 patients met criteria for the inclusion in the study: 92 in the early-onset (EO) and 68 in the late-onset (LO) group. The median follow-up was 10 years (range 2- 34 years). A family history of IBD occurred more frequently in EO compared to LO (26% vs 4%; p < 0.0007). Ileocolonic location, upper gastrointestinal involvement and perianal disease occurred more frequently in EO compared to LO (56% vs 21% p < 0.0001; 17% vs 3% p < 0.009; 38% vs 19% p < 0.01 respectively). Disease behavior at diagnosis was inflammatory in approximately 60% in both group, however progression to complicated disease during follow-up occurred more frequently in EO (40% vs 10% p < 0.002). Compared to LO, EO had increased need for steroids and anti-tumor necrosis factor (TNF) alpha during the first two years from diagnosis (41% vs 6%, p < 0.003 and 15% vs 4%, p < 0.05 respectively). The cumulative probability of receiving steroids, immunosuppressant and anti-TNF alpha within 10 years from diagnosis in EO and LO was 81% and 58% (p=0.004), 58% and 35% (p=0.04), 36% and 16% (p=0.01) respectively. There was no significant difference between the two groups regarding the cumulative probability of surgery within 10 years.

Conclusion: At our knowledge, this is the first Italian study on clinical presentation and course of CD according to age of onset. Our data are consistent with the literature being ileocolonic location and greater proportion of complicated behavior more common in EO CD. The course of disease in LO CD is more stable and less aggressive than EO CD and should be taken into account when discussing therapeutic choices.

Disclosure of Interest: None declared

P0949 DIAGNOSTIC DELAY IN IBD: A COMPARISON IN THE LAST THIRTY YEARS, AN ITALIAN MULTICENTRIC STUDY

L. Cantoro¹, A. Di Sabatino², C. Papi³, G. Margagnoni³, S. Ardizzone⁴, A. Massari⁴, P. Giuffrida², R. Monterubbianesi¹, A. Kohn¹

¹Gastroenterology, Azienda Ospedaliera San Camillo-Forlanini, Rome, ²First Department of Medicine, Fondazione IRCCS Policlinico San Matteo, Pavia, ³Gastroenterology and Hepatology Unit, Azienda Ospedaliera San Filippo Neri, Rome, ⁴Gastroenterology and IBD Unit, Luigi Sacco University Hospital, Milan, Italy

Contact E-mail Address: laura.cantoro@hotmail.it

Introduction: The diagnosis of inflammatory bowel disease (IBD) continues to present difficulties due to unspecific symptoms and limited test accuracies. Therefore IBD patients are still under-diagnosed or diagnosed with serious delay. Diagnostic delay, particularly in Crohn’s disease (CD), seems to have an important clinical impact

Aims & Methods: The aim of our study was to examine whether diagnostic delay in IBD has changed over the last thirty-three years and to investigate its correlation with CD phenotype and Ulcerative Colitis (UC) location at diagnosis. Cases included all IBD patients recorded in the registry of four IBD referral Centres in Italy. Diagnostic delay was calculated from the onset of the symptoms indicative of CD or UC to the definitive diagnosis. Data reported included date of birth, gender, IBD location and CD behavior at diagnosis, according to the Montreal classification.

Results: Of 3393 IBD patients, 2499 (74%) had a diagnostic delay ≥ 1 month, 1046 (31%) ≥ 12 month. Median diagnostic delay was 3 months, interquartile range (IQR) 0 to 13 (7 months in CD, IQR 1 to 25 and 2 months in UC, IQR 0 to 7). Mean diagnostic delay was 19, standard deviation (SD) 45, (significantly higher in CD than UC, 29 vs 11 months, SD 54 vs 34, p < 0.0005). In CD, mean diagnostic delay was higher in patients with penetrating/stricturing behavior at diagnosis (n=870) compared to patients with inflammatory behavior at diagnosis (n=667), (32 vs 23 months, SD 49 vs 57, p < 0.0005). 242 patients were diagnosed between 1952-1979 (historical cohort), while 3151 were diagnosed between 1980 and 2013 (modern cohort). Mean diagnostic delay was significantly higher in the historical cohort in comparison to the modern cohort (31 vs 18 months, SD 58 vs 44, p < 0.0005). IBD patients belonging to the modern cohort were stratified according to the time of diagnosis into three subgroups diagnosis (1980-89, 1990-99, 2000-13). There was no significant difference in the mean diagnostic delay between the three periods (18, 17 and 19 months, SD 41,37 and 50 respectively). Mean diagnostic delay in CD of modern cohort is significantly higher in the subgroup of patients ≥ 40 years at diagnosis(A3) in comparison to patients ≤40 years, 39(SD 74) vs 20(SD 33) months, p < 0.001. No significant difference was found in the mean diagnostic delay according to gender or disease location at diagnosis. No significant difference was found in the mean diagnostic delay according to gender or disease location at diagnosis.

Conclusion: Diagnostic delay in IBD was significantly decreased in recent years (1980-2013) in comparison to the past (1952-1979), however it did not change over the last thirty-three years, despite increasing the diagnostic tools. Compared with UC, diagnostic delay is higher in CD especially in penetrating/stricturing phenotype at diagnosis or age at diagnosis higher than 40 years.

Disclosure of Interest: None declared

P0950 IN-VIVO AXIAL-STRAIN SONOELASTOGRAPHY HELPS DISTINGUISH ACUTELY-INFLAMED FROM FIBROTIC TERMINAL ILEUM STRICTURES IN PATIENTS WITH CROHN’S DISEASE

L. M. Sconfienza¹, L. C. Pescatori¹, F. Cavallaro², G. E. Tontini², L. Pastorelli³, M. Vecchi², F. Sardanelli¹

¹Radiology, ²Gastroenterology, ³IRCCS Policlinico San Donato, San Donato Milanese, Italy

Contact E-mail Address: lorenzo.carlo.pescatori@gmail.com

Introduction: A number of radiological examinations are available to evaluate the terminal ileum, all with different accuracy in detecting ileal stenosis. A critical issue, however, is the possibility of differentiating inflammatory from fibrotic strictures in patients affected by terminal ileum Crohn's Disease.

Aims & Methods: To ascertain whether RTS could in-vivo differentiate fibrotic from inflammatory terminal ileum strictures in patients with Crohn’s disease, using magnetic resonance enterography (MRE) as a reference standard, 13 patients (10m,3f; median[interquartile interval]age=40[33-48]years; median C-reactive protein (CRP)=0.9[0-1.8]mg/dl; median disease duration=46[29-205]months; median Harvey-Bradshaw Index (HSI)=3[2.75-5.25]) affected by terminal ileum Crohn’s disease were prospectively included. Patients underwent MRE, evaluating T2 hyperintensity, perivisceritis, transmural contrast uptake. RTS was performed on terminal ileum. Short-axis scans were performed, each cross-section was ideally subdivided into eight circular sectors. Colour map provided by RTS was translated into a semiquantitative scale (1=red; 2=green; 3=blue).

Results: At MRE, T2 hyperintensity was seen in 7 patients, perivisceritis in 7, contrast uptake in 7. Accordingly, 7 patients were classified as having an inflammatory stricture and 6 a fibrotic one. Total median RTS score was significantly lower in patients with inflammatory stricture (16[14-16]) than that (19[18-20.75]) in patients with fibrosis (P=0.002). The same result was found when the four most superficial quadrants of the loop were considered (7[6-7]vs.10[9.25-10]; P=0.003). No significant correlation was seen between RTS-HSI (r=-0.153; P=0.635), RTS-CRP (r=0.362; P=0.247), RTS-disease duration (r=0.224; P=0.483).

Conclusion: RTS is a promising imaging modality to differentiate in-vivo inflammatory from fibrotic terminal ileum strictures in patients with Crohn’s disease.

Disclosure of Interest: None declared

P0951 COULD HISTOLOGICAL LESIONS PREDICT REACTIVATION IN ULCERATIVE COLITIS PATIENTS WITH MUCOSAL HEALING?

L. Laterza¹, S. Bibbò¹, A. C. Piscaglia¹², V. Arena³, M. Brisigotti⁴, G. Fabbretti⁴, M. L. Stefanelli², E. Gaetani¹, V. Cesario², G. Cammarota¹, F. Scaldaferri¹, A. Gasbarrini¹

¹Internal Medicine and Gastroenterology, Catholic University of Rome, Rome, Italy, ²Gastroenterology and Endoscopy Unit, State Hospital, Borgo Maggiore, San Marino, ³Institute of Pathology, Catholic University of Rome, Rome, ⁴Institute of Pathology, Infermi Hospital, Rimini, Italy

Contact E-mail Address: laterza.lucrezia@gmail.com

Introduction: Mucosal healing (MH) is a potential target in the treatment of patients with ulcerative colitis (UC), reducing the need for surgery and the risk of colorectal cancer. MH lowers the risk of disease reactivation, but some patients relapse in spite of the presence of MH. It is reasonable to think that the microscopic disease activity beyond MH could explain these cases.

Aims & Methods: Our aim is to assess how many patients with MH have a microscopic disease activity and what kind of lesions are associated with mid-term n (after 6 and 12 months).

Our aim is to assess how many patients with MH have a microscopic disease activity and what kind of lesions are associated with mid-term reactivation (after 6 and 12 months).

We retrospectively enrolled UC patients showing MH, expressed as Mayo 0 at colonoscopy, and undergone multiple biopsies during the same exam. We reviewed the corresponding histological lesions evaluating the presence of the typical histological lesions associated with UC, such as acute or chronic inflammatory infiltrate, basal plasmacytosis, basal lymphoid aggregates, stromal changes, lamina propria eosinophils, crypt branching, crypt distortion, crypt atrophy/depletion, cryptitis, crypt abscesses, surface irregularity, mucin depletion, erosions and Paneth cell metaplasia. We evaluated the number of clinical reactivation 6 and 12 months after baseline colonoscopy.

Results: Among 63 enrolled patients, only 2 showed no histological lesions. The most common lesion was chronic inflammatory infiltrate (81%) followed by basal lymphoid aggregates (60%), acute inflammatory infiltrate (46%) and crypt distortion (33%). After 6 and 12 months, 14% and 22% of patients relapsed, respectively. The most prevalent lesion in patients relapsing after 6 months was chronic inflammatory infiltrate (100% of relapsers vs 76% of non-relapser), followed by acute inflammatory infiltrate (63% vs 40%), basal lymphoid aggregates (63% vs 62%), basal plasmacytosis (50% vs 12%, p < 0.05) and lamina propria eosinophils (50% vs 10%, p < 0.05). After 12 months, chronic inflammatory infiltrate was found in 90% of relapsers vs 83% of non-relapsers, basal lymphoid aggregates in 70% vs 53% and acute inflammatory infiltrate in 50% vs 44%, basal plasmacytosis (50% vs 8%, p < 0.05) and lamina propria eosinophils (40% vs 11%, p < 0.05), respectively.

Conclusion: A microscopic disease activity persists in the major part of patients with MH. Basal plasmacytosis and lamina propria eosinophils are more frequent in patients with disease reactivation after 6 and 12 months.

Disclosure of Interest: None declared

P0952 INFLIXIMAB LEVEL AND ANTI-DRUG ANTIBODY IN INFLAMMATORY BOWEL DISEASE PATIENTS LOSING RESPONSE: ASSAY AFTER OPTIMIZATION AND OUTCOME AT ONE YEAR

L. Guidi¹, M. Marzo¹, B. Tolusso², D. Pugliese¹, G. Andrisani¹, C. Felice¹, R. Landi¹, S. Canestri², E. Gremese², I. De Vitis¹, A. Papa¹, G. L. Rapaccini¹, A. Armuzzi¹

¹Internal Medicine and Gastroenterology, ²Rheumatology, Catholic University Sacro Cuore, Roma, Italy

Contact E-mail Address: lguidi@rm.unicatt.it

Introduction: Therapeutic drug monitoring is claimed to be an important tool in tailoring infliximab therapy to the clinical status of inflammatory bowel disease (IBD) patients. However, cut-off values for infliximab trough levels (TL) and anti-drug antibodies (ATI) need to be established for each assay method and validated in the clinical setting.

Aims & Methods: Aim of our study was to evaluate infliximab TL and ATI in patients losing response and to identify cut-off values after drug optimization, which could be significantly related to clinical outcomes at one year. We studied 71 IBD patients, 42 affected by Crohn’s disease (CD) and 29 by ulcerative colitis (UC). They were on maintenance treatment with infliximab after initial response to the induction course and had experienced a loss of response defined as worsening of clinical symptoms and rise in CRP or evidence of endoscopic disease activity. We collected blood for assay of trough levels and antibodies to infliximab by ELISA method (LisaTracker-Duo Infliximab, Theradiag, Marne-la-Vallée, France). According to manufacturer instructions, levels of detection were 0.1 μg/ml for TL and 10 ng/ml for ATI. We recorded clinical status and CRP levels after drug optimization (dose increase and/or interval shortening), after six months and after one year. All TL and ATI determinations were performed in a single laboratory session and the clinicians were blinded to the results, which did not influence the clinical decisions.

Results: Of the 71 IBD patients, 15 (21%) were on concomitant treatment with azathioprine/6MP and 55 (77%) were studied after infliximab optimization. Clinical follow-up at 12 months was available for 49 of them. ATI were detected in 26/71 patients (36%) while TL were undetectable in 13/71 (17%). ATI and TL were negatively correlated (Spearman’s rho -0.53, p=0.0001). By ROC analysis we found that achieving a TL >4.05 μg/ml after optimization was predictive of clinical response after 12 months (AUC 0.648, sensitivity 60%, specificity 75%, p=0.05). The same cut-off was predictive of normal CRP both after 6 months (AUC 0.652, sensitivity 59%, specificity 77%, p=0.05) and after 12 months (AUC 0.677, sensitivity 59%, specificity 80%, p=0.02). The presence of ATI levels >11 ng/ml was predictive of high CRP at 6 months (AUC 0.653, sensitivity 48%, specificity 82%, p=0.029).

Conclusion: Monitoring infliximab TL after dose optimization and/or interval shortening for loss of response could help in predicting those patients that will display a clinical and biological (CRP) response in the following year. Further prospective studies will clarify if applying treatment algorithms based on therapeutic drug monitoring will reveal as cost-effective in IBD.

Disclosure of Interest: L. Guidi Lecture fee(s): MSD, AbbVie, Takeda, Zambon, Consultancy: MSD, AbbVie, Mundipharma, M. Marzo: None declared, B. Tolusso: None declared, D. Pugliese: None declared, G. Andrisani: None declared, C. Felice: None declared, R. Landi: None declared, S. Canestri: None declared, E. Gremese: None declared, I. De Vitis: None declared, A. Papa: None declared, G. L. Rapaccini: None declared, A. Armuzzi Financial support for research: MSD, Lecture fee(s): AbbVie, Astra-Zeneca, Chiesi, Ferring, Hospira, MSD, Otsuka, Takeda, Zambon, Consultancy: AbbVie, Hospira, Lilly, MSD, Mundipharma, Pfizer, Sofar, Takeda

P0953 PRESENCE OF PRIMARY SCLEROSING CHOLANGITIS DOES NOT CHANGE LEVELS OF GUT BARRIER FAILURE BIOMARKERS (I – FABP AND CCK18) IN PATIENTS WITH ULCERATIVE COLITIS

P. Drastich¹, L. Bajer¹, M. Kverka², S. Coufal², J. Brezina¹, M. Benes¹, H. Tlaskalova - Hogenova², J. Spicak¹

¹Hepatogastroenterology, Institute for Clinical and Experimental Medicine, ²Institute of Microbiology ASCR, Prague, Czech Republic

Contact E-mail Address: lukasbajer1@gmail.com

Introduction: Primary sclerosing cholangitis (PSC) is a progressive disease of the biliary tree characterised by inflammation, fibrosis and stenoses, and often associated with ulcerative colitis (UC); condition characterized by leaky gut. However, UC associated with PSC (“PSC – UC” or “PSC – IBD”) is described as a phenotype distinct from the conventional UC. Our aim was to compare serum levels of biomarkers of gut barrier damage in PSC-UC, UC and healthy subjects.

Aims & Methods: We used ELISA to analyze intestinal fatty acids binding protein (I-FABP) and caspase-cleaved keratin 18 (ccK18) in 74 individuals (38 with PSC, 19 with UC, 17 healthy controls) and 38 individuals (23 with PSC, 9 with UC, 6 healthy controls), respectively. Furthermore, we compared the levels of either biomarker with standard clinical (e.g. colitis extent and severity) and laboratory parameters (CRP, AST, ALT, ALP, GGT, INR).

Results: There is no significant difference between PSC-UC, UC and healthy subjects in I-FABP [median (IQR)] 503.9 (0.0 - 1548.0), 454.1 (0.0 - 747.3), 769.3 (220.9 - 1027.0) or ccK18 [median (IQR)] 174.1 (99.93 - 423.0), 90.08 (67.46 - 205.9), 98.7 (51.05 - 174.7). When the liver involvement is disregarded, I-FABP have a tendency to be higher in patients with pancolitis as compared with patients with partial colon involvement (p=0.07). There is no statistically significant difference in serum I-FABP or ccK18 depending on colitis severity (without colitis, remission, mild, moderate and severe).

Conclusion: Neither I-FABP, nor ccK18 differs between PSC-UC and UC. In patients with pancolitis, I-FABP has a tendency to be higher compared to patients with smaller extent of colitis.

Disclosure of Interest: None declared

P0954 EFFICACY OF LOW DOSE CT FOR EVALUATION OF DISEASE ACTIVITY IN ULCERATIVE COLITIS

M. Shiraki¹

¹Department of Gastroenterology, Tohoku Rosai Hospital, Sendai, Japan

Contact E-mail Address: sankara@qf6.so-net.ne.jp

Introduction: It is important to assess the disease activity and extent of involvement in ulcerative colitis patient. Endoscopic examination, however, carries a risk of perforation of the colon often requiring surgery because of mucosal vulnerability, especially in patients with ulcerative colitis relapsing. Recently, it has been reported that cross-sectional imaging techniques can be used as a diagnostic tool for the evaluation of inflammatory bowel disease, nevertheless, there have been few reports on the efficacy of low dose CT for ulcerative colitis. We report here the efficacy of low-dose CT for ulcerative colitis during active period.

Aims & Methods: The purpose of this study is to investigate the diagnostic performance of low-dose CT for evaluation of disease activity in ulcerative colitis patient. The patients with relapsing ulcerative colitis between July 2013 and April 2014 were included in this study. All patients had undergone sigmoidoscopy and low-dose CT scan with the weight-based intravenous contrast protocol. The colon CT image was divided into six segments: rectum, sigmoid colon, descending colon, transverse colon, ascending colon, and caecum, then we evaluated wall thickening, stratification, contrast enhancement and mesenteric vascular engorgement, assigning a CT score to each segment. Further, we calculate a total CT score by the sum of CT scores of 6 segments. To assess endoscopic severity, Ulcerative Colitis Colonoscopic Index of Severity (UCCIS) was used. All patients were interviewed before examination to calculate Mayo partial score to assess the clinical severity. We investigated the correlation between those CT scores and UCCIS. The correlation between partial Mayo score and total CT score also investigated. For the correlation analysis, the Spearman rank correlation analysis was used. For comparison between two groups we used the Mann-Whitney U test.

Results: Twenty three cases of ulcerative colitis were included in this study. We achieved a 62.3 % reduction of radiation exposure by adjusting the scan conditions and reconstruction conditions (P < 0.00326). The average partial Mayo score of the cases was 4.4 ± 2.0. We observed a high degree of correlation between the sum of the CT scores of the rectum and sigmoid colon and the sum of the UCCIS of the rectum and sigmoid colon (ρ = 0.629). Although the UCCIS of the rectum and sigmoid colon segment calculated by sigmoidoscopy and partial Mayo scores did correlate (ρ = 0.456), the correlation between the total CT score showed better correlation with the partial Mayo score (ρ = 0.643).

Conclusion: The endoscopic examination is important for evaluate disease severity in ulcerative colitis relapsing; however, it is often difficult to perform total colonoscopy due to mucosal vulnerability. On the other hand, CT can provide diagnostic images without preparation or invasiveness. This study suggested that low-dose CT could provide more effective images to assess the disease activity of ulcerative colitis compared with sigmoidoscopy.

Disclosure of Interest: None declared

P0955 ASSESSMENT OF BACTEROIDETES GENOTYPES IN BIOPSIES OF INFLAMMATORY BOWEL DISEASE (IBD) PATIENTS. A CASE-CONTROL STUDY

M. Barreiro-De Acosta¹², R. Sueiro³, A. P. De Felipe³, L. Uribarri-Gonzalez¹², R. Ferreiro-Iglesias¹², J. M. Leiro³, J. E. Domínguez-Munoz¹²

¹University Hospital of Santiago de Compostela, ²Foundation for research in Digestive Diseases, ³Institute of Food Research and Analysis, University of Santiago de Compostela, Santiago de Compostela, Spain

Contact E-mail Address: info@fienad.org

Introduction: The exact role of gut microbiota on the etiopathogenesis of IBD, both Crohn’s disease (CD) and ulcerative colitis (UC), is not well known. Most studies of human gut microbiota rely on the non-invasive collection of stool samples. However, the analysis of the fecal microbiota may not reflect the role of the mucosa-associated microbes which live in close proximity to the intestinal epithelium and that are in contact with the cells of the innate immune system directly involved in the inflammatory response.

Aims & Methods: The aim of this study was to investigate the genotypes of Bacteroidetes microbiota from colon biopsies of IBD patients and to determine their relationship with the endoscopic activity of the disease.

Methods: A prospective case-control study was designed. Colon biopsies from consecutive IBD patients and healthy controls (HC) (healthy subjects undergoing colonoscopy for colon cancer screening and having a healthy colon mucosa) were included. Inactive UC was defined as a Mayo endoscopic subscore of 0. Inactive CD was defined as a SES-CD score ≤2. Microbiota was characterized by using a restriction fragment length polymorphism (RFLP) analysis on PCR products targeting the 16SrRNA genes of Bacteroidetes digested with HinfI, PciI, DpnII and AciI. RFLP and sequencing analysis indicated that a a total of 8 genotypes of Bacteroidetes called N1 and C1-C7 (of which N1 genotype is probably a strain of Bacteroides dorei and C1, and maybe C2, strains of B. vulgatus) were detected in all the biopsy samples analyzed. Results are shown as percentages.

Results: 53 consecutive IBD patients (24 UC and 29 CD) and 20 HC were included. 8 patients presented inactive UC (iUC) and 16 active UC (aUC). In addition, 21 CD patients presented active CD (aCD) and 8 inactive CD (iCD). The number of genotypes present in biopsies from IBD patients was higher than in HC, in whom only the N1 (58%) and C1 (42%) genotypes appear. While the presence of N1 genotypes was relatively constant in patients with active CD and active/inactive UC, the percentage of C1 genotype in these patients was low (between 20% and 26%) compared to HC and iUC (51%). The C4 genotype never appeared in control samples and it was present in only 4% of iUC and iCD biopsies, whereas it was present in 13% and 14% of patients with aUC and aCD respectively. Moreover, C3 genotype was higher in iUC (8%) than with aUC (3%) and CD (3% with active and inactive patients). The C2, C3, C5, C6 and C7 genotypes appeared sporadically in biopsies of IBD but never in HC.

Conclusion: Bacteroidetes genotypes in colon biopsies differ between IBD patients and HC. These genotypes, and especially the C4 genotype, may be used as biomarkers for improving the diagnosis of CD and UC, as well as to investigate their potential role in pathogenesis.

Disclosure of Interest: None declared

P0956 REDISCOVERY OF THE ANTI-PANCREATIC ANTIBODIES AND EVALUATION OF THEIR PROGNOSTIC VALUE IN A PROSPECTIVE CLINICAL COHORT OF CROHN'S PATIENTS: THE IMPORTANCE OF SPECIFIC TARGET ANTIGENS (GP2 AND CUZD1)

M. Papp¹, N. Sipeki¹, I. Altorjay¹, G. L. Norman², Z. Shums², D. Roggenbuck³, K. Fechner⁴, P. Antal-Szalmas⁵, G. Veres⁶, P. L. Lakatos⁷

¹Institute of Medicine, Department of Gastroenterology, University of Debrecen, Debrecen, Hungary, ²Inova Diagnostics, Inc., San Diego, CA, United States, ³Faculty of Natural Sciences, Lausitz University of Applied Sciences, Senftenberg, ⁴Institute of Experimental Immunology, Euroimmun AG, Lubeck, Germany, ⁵Department of Laboratory Medicine, University of Debrecen, Debrecen, ⁶1st Department of Pediatrics, ⁷1st Department of Medicine, Semmelweis University, Budapest, Hungary

Contact E-mail Address: papp.maria@med.unideb.hu

Introduction: Glycoprotein 2 (GP2) and CUB zona pellucida-like domain 1 (CUZD1) belong to protein families involved in gut innate immunity processes and have recently been identified as a specific target of anti-pancreatic autoantibodies (PAbs) in Crohn’s disease(CD). The aim of the present study was to determine the predictive potential of novel target specific PAbs regarding determination of disease phenotype, therapeutic strategy and long-term disease course in a prospective referral adult CD patient cohort.

Aims & Methods: Sera of 458 consecutive well-characterized IBD patients (CD: 271 and UC: 187) from a single referral IBD center and 100 healthy subjects were tested by enzyme-linked immunosorbent assay (ELISA) with isoform 4 of recombinant GP2 (anti-MZGP2 and anti-GP2 IgA/IgG) and indirect immunofluorescence test (IIFT) system with GP2 or CUZD1 expressing transfected HEK 293 cells (anti-rPAg2 and rPAg1 IgA/IgG). Clinical data were available on evolvement of complicated disease or surgical interventions as well as disease activity and medical treatment during the prospective follow-up (median, [IQR]: 108 months [65-178]).

Results: 12.4% and 20.8% of CD patients were positive for IgA/IgG type of anti-GP2 and anti-CUZD1, respectively, with a significant difference compared to UC and controls (p < 0.01 for both). PAb status was not associated with actual disease activity and showed long-term stability. Agreement among three different anti-GP2 assays was good (kappa: 0.44-0.70). At diagnosis, 45% of the patients had ileocolonic disease and 79.7% had inflammatory behavior, while 52% had complicated disease behavior, 35.1% had perianal disease and 41.1% had at least one resective surgery at last follow-up. Clinical associations were different for anti-GP2 and anti-CUZD1 antibodies. Presence of different anti-GP2 antibodies was associated with pediatric onset (p=0.012), ileal involvement (p=0.032), stenosing (p=0.017) and penetrating (p=0.028) disease behavior at diagnosis and PSC (p=0.038). In contrast, presence of anti-CUZD1 was associated with colonic involvement (p=0.041) and cutaneous manifestations (p=0.044). In a group of patients with pure inflammatory luminal disease at time of the diagnosis, positivity for PAbs, mainly IgA subtypes, predicted a faster progression towards complicated disease course in time-dependent models. In Kaplan-Meier analysis, time to surgery or development of perianal disease was associated with anti-GP2 IgA (pLogRank < 0.01) or anti-CUZD1 IgA (pLogRank < 0.001) positivity, respectively. Anti-CUZD1 IgA remained an independent predictor in multivariate Cox-regression model including age at diagnosis, sex, disease location and behavior and frequent relapse as potential confounders (HR: 3.43, 95%CI: 1.68–7.02, p < 0.001).

Conclusion: The present prospective follow-up study has shown that specific PAbs (especially IgA subtype) are predicting complicated disease course including the development of perianal disease in CD.

Disclosure of Interest: None declared

P0957 RISK MATRIX FOR PREDICTION OF DISEASE PROGRESSION IN A REFERRAL COHORT OF PATIENTS WITH CROHN’S DISEASE

P. L. Lakatos¹, N. Sipeki², G. L. Norman³, Z. Shums³, P. Antal-Szalmas⁴, G. Veres⁵, M. Papp²

¹1st Deparment of Medicine, Semmelweis University, Budapest, ²Institute of Medicine, Department of Gastroenterology, University of Debrecen, Debrecen, Hungary, ³Inova Diagnostics Inc., San Diego, United States, ⁴Department of Laboratory Medicine, University of Debrecen, Debrecen, ⁵1st Department of Pediatrics, Semmelweis University, Budapest, Hungary

Contact E-mail Address: papp.maria@med.unideb.hu

Introduction: Early identification of patients with Crohn’s disease (CD) at risk for subsequent complications is essential for adapting treatment strategy. The aim of the present study was to develop a prediction model including clinical and serology markers for assessing the probability of developing advanced disease 3, 5 and 7 years after diagnosis in a prospective referral CD cohort.

Aims & Methods: 271 consecutive CD patients (42.4% males, median follow-up: 10.9 years) were included. ASCA IgA and IgG and anti-OMP Plus^TM IgA antibodies were determined by QUANTA Lite® ELISA (Inova Diagnostics, San Diego, CA), cut-off 25 U/ml. Detailed clinical phenotypes were determined prospectively from diagnosis during the follow-up by reviewing the patients’ medical charts. The analysis was limited to patients with inflammatory disease behaviour at diagnosis. Total exposure to steroids, azathioprine or anti-TNFs were 88.2%, 73.8% and 41.7%, respectively. At diagnosis, 45% had ileocolonic disease and 79.7% had inflammatory behaviour, while 52% had complicated disease behaviour and 41.1% had at least one resective surgery at last follow-up. Two definitions were used for advanced disease: 1.) having intestinal resection or progression in disease behaviour and 2.) having intestinal resection, progression in disease behaviour, or need for thiopurines (IBSEN definition).

Results: ASCA IgA and/or IgG (but not anti-OMP Plus IgA status), disease location, and need for early azathioprine were included in the 5-year prediction matrix. The probabilities of advanced disease during this period varied from 6.2% to 55% depending on the combination of predictors. The 3- and 7-year ASCA-based model resulted in probabilities of advanced disease ranging from 0 to 45.5% and from 11.1% to 64.7%. In addition, the model including ASCA, disease location, and early need for steroids but not age at onset, was only predictive for the outcome at 5-years if the IBSEN definition was used. In contrast, the association was lost if the need for azathioprine was excluded from the advanced disease definition. Similar findings were obtained from in a Cox regression analysis, the combination of ASCA, location and early azathioprine was associated with the probability to develop advanced disease (pLogRank < 0.001), while the original model combining ASCA, early steroids and location failed to predict disease progression.

Probability of developing advanced disease 5-years after the diagnosis in patients with initial inflammatory disease based on association between ASCA IgA and IgG positivity, disease location and need for early azathioprine (AZA).

B1 behavior at diagnosis		colon only	ileal
ASCA positive	early AZA YES	50.0%	55.0%
	early AZA NO	30.8%	29.0%
ASCA negative	early AZA YES	11.1%	22.2%
	early AZA NO	6.2%	18.8%

Conclusion: Our prediction models identified substantial differences in the probability of developing advanced disease in the short and intermediate course of CD. Markers identified in this referral cohort were different from those previously published in the population-based cohort suggesting that different prediction models should be used in referral setting.

Disclosure of Interest: None declared

P0958 ON THE ORIGIN OF CRP IN CROHN’S DISEASE: ROLE OF THE EXTRAMURAL COMPONENT

M. Serio¹, A. Pierro², K. Efthymakis¹, F. Laterza¹, G. Maselli², A. Milano¹, A. Bonitatibus¹, G. Sallustio², M. Neri¹

¹Medicine and Aging Sciences and CESI, Universita` “G. D’Annunzio", Chieti, <sup>2</sup>Radiology Department, Fondazione di Ricerca e Cura ‘‘Giovanni Paolo II’’, Universita` Cattolica del Sacro Cuore, Campobasso, Italy

Contact E-mail Address: mariaelenaserio@yahoo.it

Introduction: Due to the full thickness involvement of the bowel wall or complications, Crohn's disease (CD) evaluation is the result of an integration of endoscopy (the gold standard) with clinical, laboratory and radiological data. The role of MRI, which excels in identyfing extramural signs of inflammation, is still unclear in CD follow-up. Moreover it is still debated whether CRP serum levels increase is due to mucosal or mural/extramural inflammation, not only via liver production but also from extrahepatic sources such as hypertrophy of the mesenteric fat, a CD common feature.Increased mesenteric fat density assessed by CT was found to correlate with plasma CRP levels in CD patients¹.

Aims & Methods: Aim of this study was to correlate enteric and extraenteric inflammatory MRI findings with endoscopic severity and CRP in a group of CD patients.

52 consecutive patients with endoscopically proven CD underwent MRI enterography for the staging at diagnosis or activity assessment (68/32%). Endoscopic activity was scored through the SES-CD (range 0-40) with active mild, moderate ad severe disease defined as 4-10,11-19 and >20 respectively. MRI activity was scored through the Magnetic Resonance Enterography Global Score (MEGS, range 0-296), which integrates both mural and extramural items, namely lymph node, fistula, abscess and comb sign, with active disease defined as ≥ 1 score. For all participants CDAI was completed and CRP and fecal calprotectin (FC) were also measured (positivity cut-off respectively >0.50mg/dl and >150μg/gr). Fibrofatty proliferation (creeping fat) of the mesentery was qualitatively defined a bowel loop separation ≥ 3 cm.

Results: We enrolled 20M/32F mean age 38 ± 15 ys, mean CD duration 5 ± 5 ys.SES-CD and MEGS correlated well between them and with clinical and biological activity(table). According to SES-CD 62% of patients had mild disease, 19% moderate and 5% severe.Increasing severity at endoscopy was significantly correlated with trasmural/extramural involvement, only with CRP positivity (p=0.007). MRI did not show ability to distinguish endoscopic severity (p=0.14), but revealed trasmural/extramural signs of inflammation in 60% of patients in remission, 84% mild and 100% with moderate and severe disease, mostly with CRP positivity. Moreover CRP positivity was associated with the presence of extraintestinal(p=0.006; lymph nodes p=0.009, combsign p=0.001 and abscess p=0.005), not of mural involvement (p=0.4). Mean CRP levels increased according to the number of extramural signs of inflammation (from absence to 4 signs p=0.01), while no correlation was seen with SES-CD severity (p=0.7), phenotype (p=0.4) or mural inflammation (p=0.7). Patients with hypertrophy of mesenteric adipose tissue showed higher levels of CRP than those without (4.2 ± 4 mg/dl vs 1.9 ± 3.2 p=0.005).

	SES-CD	CDAI	CRP	FC
MEGS	r=0.42 p < 0.001	r=0.59, p < 0.001	r=0.43 p < 0.005	r=0.27, p < 0.01
SES-CD		r=0.51, p < 0.001	r=0.39 p < 0.005	r=0.35, p < 0.01

Conclusions: Transmural inflammation, which is more frequent in severe disease, may still be present regardless of endoscopical activity.Positive CRP is significantly correlated to extramural activity in CD patients, thus suggesting the need of MRI for the staging of the disease independently from endoscopic severity. Moreover these data suggest that mesenteric fat may contribute to the increased CRP production.

Disclosure of Interest: None declared

P0959 IS MONITORING ANTI TNFA TROUGH LEVELS IN THE CLINICAL PRACTICE COST-EFFECTIVE? THERAPEUTIC IMPLICATIONS AND COST: A PRELIMINARY AND RETROSPECTIVE STUDY OF TWO NON TERTIARY SPANISH HOSPITALS

M. Arias¹, I. Guerra², E. Fernandez-Marcote³, M. Hernández Tejero², A. Algaba², L. A. Castillo¹, F. Bermejo², J. Jimenez⁴, E. Quintanilla¹, L. R. Rábago¹

¹Gastroenterology, Hospital Severo Ochoa, Leganés, ²Gastroenterology, Hospital Universitario de Fuenlabrada, Fuenlabrada, ³Gastroenterology, Hospital Severo Ochoa, Leganes, ⁴Biochemistry Laboratory, Hospital Severo Ochoa, Leganés, Spain

Contact E-mail Address: lrabagot@gmail.com

Introduction: The loss of response to antiTNFa treatment occurs in about 13-18% of the patients/year. The cost and adverse events of these drugs drugs can make therapeutic monitoring of antiTNFa trough levels an adequate strategy for treatment optimization

Aims & Methods: This is a retrospective multicentric study with 40 IBD patients(pts) -77.5% Crohn disease (CD), 17.5% ulcerative colitis (UC) and 5% of undetermined colitis (IC)- treated with antiTNFa (IFX 52.5% or ADA 47.5%), and 72.5% of pts were also on immunomudulator therapy (IMM). The mean age was 42.5(22-76) with a 50% of female. AntiTNFa trough levels were measured by an ELISA assays (Sanquin).The consideration of supratherapeutic levels was made in relation with the range of the Elisa assay. Patients were included in: Group 1 (57.5%) 23 out of 40 pts with secondary loss of response (SLR) to IFX (20pts) or ADA (3pts). Group 2: (40%) 16 out of 40 clinically asymptomatic pts on ADA treatment had ADA trough levels monitored per protocol during the follow up, Group 3 (2.5%,1/40 pts) with mucosal healing.

Results: Group 1: 17.5% pts(4/23) had normal levels, 30% of pts (7/23) had supratherapeutic levels and 52.5% (12/23) had low levels and 25 % of them (3pts) had also detectable antiTNFa antibodies. 78.7% of pts (18 out of 23) of Group 1 were on IMM. 8 out of 23 pts of Group 1 with SLR had not worsening of inflammatory analytical markers 3 out of these 8 pts (37.5%) had low therapeutic levels without intensification of treatment, 2 out of those 8 (25%) had supratherapeutic levels.

Group 2: 31.2 % of pts (5/16) treated with ADA and clinically asymptomatic had supratherapeutic levels, 1 out of those 16 pts was on intensified treatment, 25% of pts (4/16) had low therapeutic levels with 2 pts on intensified therapy and 43.7% (7/16) had normal levels.Therefore we had to perform changes in 28 pts. In order to calculate the treatment-cost we use the standard cost of the different antiTNFa therapies at our hospital, considering if it is the case the price of the induction and the maintenance therapy. The cost of treatment optimization by taking into account the results of antiTNFa trough levels measurement and antibodies to antiTNFa (dose escalation if low levels, switching to another antiTNFa or switching to a different class of biologic agent if therapeutic or supratherapeutic levels) would have been 467127 euro per year for these 28 pts. Had we treated in the classic way without monitoring levels the cost would have been 530369€, So there is a 63000 euro/pt/year of savings (2250 euro per pts/year).

Conclusion: 1º Hardly 17.5 of pts with SLR had normal antiTNFa levels and 30% had high levels that should be changed to a different class of biologic agent. 2 º Monitoring ADA trough levels during their normal F-U found a 25% of patients over-treated. 3º 37.5 % of Pts with SLR but without inflammatory analytical markers could be treated with dose escalation until new endoscopic or radiologic studies are performed. 4º The cost analysis show that monitoring antiTNFa levels is not only an effective way of pts management but also cost effective.

Disclosure of Interest: None declared

P0960 CONTRAST ENHANCED ENDOSCOPIC ULTRASOUND OF THE COLON IS A MARKER OF EARLY THERAPY RESPONSE FOLLOWING ANTI-TNF-THERAPY IN PATIENTS WITH ACUTE ULCERATIVE COLITIS

M. Ellrichmann¹, J. Bethge¹, A. Arlt¹, S. Zeissig¹, B. Brandt¹, J. Lankau¹, S. Nikolaus¹, S. Schreiber¹, A. Fritscher-Ravens¹

¹Medical Department I, Interdisciplinary Endoscopy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

Contact E-mail Address: mark.ellrichmann@uksh.de

Introduction: Though colonoscopy is an important tool in the evaluation of acute ulcerative colitis (aUC), it is limited to the mucosal surface and therefore exhibits a significant interobserver variability. As shown by our group, endoscopic ultrasound (EUS) of the colonic wall allows exact quantification gut wall with differentiation of the different layers and can therefore accurately quantify the grade of inflammation.

Aims & Methods

Aim: To evaluate EUS in sigmoid colon in patients with aUC undergoing treatment with Anti-TNF-α (adalimumab,(ADA)) for possible detection of early therapy response.

Methods: 36 patients (22m) with aUC and 20 healthy controls (HC)(12m) were examined prior and 1, 4 and 12 weeks after initiation of ADA therapy using a forward-viewing radial echoendoscope (Pentax-Hitachi, Japan). Mucosal, submucosal and total wall-thickness (TWT) were measured by EUS in the mid sigmoid. Vascularity of the gut wall was evaluated by dynamic contrast enhanced EUS (dCEUS) (contrast agent SonoVue). Contrast kinetics were quantified as Time to peak intensity (TTP). Results were compared to 20 healthy controls (HC) undergoing screening colonoscopy. The examiners were blinded to the macroscopic inflammation scores. EUS-results were correlated to the Mayo-score and histological inflammation scores (HIS).

Results: HC showed a TWT of 1.8 ± 0.03mm with clear differentiation of the different layers; TWT increased to 3.91 ± 0.21mm(p < 0.001) in patients with aUC. In patients with clinical response to ADA therapy (n=26; 72.2%) TWT was reduced by 27.7% (TWT_7d=2.5 ± 0.2mm; p=0.007) within one week when compared to baseline levels with further reduction after 4 weeks (TWT_28d=2.2 ± 0.2mm).

In patients with non-response to ADA therapy no significant changes of TWT were observed compared to baseline after 7 (TWT7d=3.7 ± 0.4mm; p=0.8) and 28 days (TWT_28d=2.9 ± 0.3mm; p=0.4) of therapy.

TTP in HC was 13.1 ± 1.3s; in aUC TTP was accelerated to 6.8 ± 0.7s (p=0.0005). In case of response TTP normalized within 1 week (TTP_d7=9.9 ± 0.8s) with p=0.008 compared to baseline. In contrast, hypervasculartity remained unchanged in patient without response to ADA therapy (TTP=6.6 ± 0.5s;p=0.9).

Prior to therapy there was a strong correlation of TWT and Mayo-scores. In contrast, no correlation was observed 1 week after ADA therapy (p > 0.05). During the entire course of ADA, a positive relation between TWT and HIS (r=0.65; p < 0.001) was seen.

Conclusion: TWT of the sigmoid measured by EUS precisely quantifies the level of inflammation in patients with aUC and proved reliability for the evaluation of early therapy response. It may become an important diagnostic tool for the judgement of mucosal healing in ADA therapy.

Disclosure of Interest: None declared

P0961 LONG-TERM OUTCOME OF INFLIXIMAB MAINTENANCE TREATMENT FOR JAPANESE PATIENTS WITH CROHN’S DISEASE

H. Tanaka¹, M. Miyakawa¹, M. Nasuno¹, S. Motoya¹

¹IBD Center, Sapporo Kosei General Hospital, Sapporo, Japan

Contact E-mail Address: hirokit@mtc.biglobe.ne.jp

Introduction: Maintenance treatment with infliximab has enabled achievement of long-term remission in patients with Crohn’s disease (CD). However, very few studies have reported on Japanese patients.

Aims & Methods: The aim of this study was to evaluate infliximab maintenance treatment for Japanese patients with CD based on long-term outcomes and related prognostic factors. Retrospective data were collected from luminal CD patients who received the standard treatment of 5 mg/kg infliximab for ≥ 14 weeks between May 2002 and August 2012 at the IBD Center, Sapporo Kosei General Hospital. The effectiveness of infliximab maintenance treatment was evaluated using sustained treatment success rates, which were estimated using the Kaplan–Meier method. Sustained treatment success was defined as a lack of treatment failure. Treatment failure was defined as follows: 1) the discontinuation of infliximab due to loss of response or side effects; 2) the need for dose escalation due to loss of response or 3) the need for abdominal surgery due to CD. Prognostic factors related to sustained treatment success rates were evaluated using log-rank tests and a multivariate Cox regression analysis.

Results: Of the 276 patients included in this study (mean age, 31.2 years), 72 were females. The mean duration of the disease was 7.5 years and the mean C-reactive protein (CRP) level at the first infliximab administration was 2.18 mg/dl. One hundred fifty-two patients had ileocolitis, 68 had ileitis and 56 had colitis. In addition, 111 patients had structuring disease, 36 had intra-abdominal fistulas and 114 had perianal disease. Concomitant treatment with immunomodulators (azathioprine or 6-mercaptopurine), 5-aminosalicylic acid, elemental diet therapy and prednisolone were administered in 197, 245, 194 and 28 patients, respectively. Before initiating infliximab therapy, 96 patients had undergone at least 1 intestinal resection and no patient had had prior use of any other anti-tumour necrosis factor antibodies. The 2-, 4-, 6-, 8- and 10-year sustained treatment success rates were 62%, 50%, 40%, 30% and 30%, respectively. In the univariate analyses, a lower CRP level at the first infliximab administration (<1.00 mg/dl; P = 0.011) and concomitant treatment with immunomodulators (P = 0.016) were significant prognostic factors for higher sustained treatment success rates. The multivariate Cox regression analysis, both of these factors identified as independent predictors of said success rate.

Conclusion: Among Japanese patients with CD receiving infliximab maintenance treatment over a period of ten years, the treatment failure rate was 70% but could be decreased by combination therapy of infliximab with immunomodulators. Conversely, a higher CRP level at the time of first infliximab administration was a prognostic factor for a poor long-term outcome.

Disclosure of Interest: H. Tanaka: None declared, M. Miyakawa: None declared, M. Nasuno: None declared, S. Motoya Financial support for research: AbbVie GK, Janssen Pharma., Lecture fee(s): Tanabe-Mitsubishi Pharma.

P0962 TREATMENT WITH MESNA AND N-3 POLYUNSATURATED FATTY ACIDS AMELIORATES EXPERIMENTAL ULCERATIVE COLITIS IN RATS

I. Triantafyllidis¹, T. Poutachidis², I. Taitzoglou³, D. Botsios⁴

¹Surgery, Veria General Hospital, Veria, ²Laboratory of Pathology, Faculty of Health Sciences, School of Veterinary Medicine, ³Laboratory of Physiology, Faculty of Health Sciences, School of Veterinary Medicine, Aristotle University, ⁴4th Department of Surgery, Papanikolaou University Hospital, Faculty of Health Sciences, School of Medicine, Thessaloniki, Greece

Contact E-mail Address: itriantafyllidhs@yahoo.gr

Introduction: Oxidative damage is a central feature of ulcerative colitis. Here we tested whether the antioxidant Mesna, when administered alone or in combination with n-3 polyunsaturated fatty acids (n-3 PUFAs), affects the outcome of Dextran Sodium Sulfate (DSS)-induced ulcerative colitis in rats.

Aims & Methods: After the induction of colitis, DSS-treated rats were further treated orally (p.o), intraperitoneally (i.p) or intrarectally (i.r) for either 7 or 14 days with Mesna, n-3 PUFAs or both. Rats were euthanized at the end of each treatment period. Clinical disease activity index was recorded throughout the experiment. At necropsy, colorectal gross lesions were scored. Colitis was scored histologically and the expression of myeloperoxidase (MPO), caspase-3, inducible nitric oxide synthase (iNOS) and nuclear factor κB (NF-κβ) in colonic tissue, was assessed by immunohistochemistry.

Results: Mesna alone was sufficient to significantly reduce colorectal tissue damage, when administered orally or intraperitoneally. Orally coadministered n-3 PUFAs enhanced this effect resulting in significant suppression of DSS colitis after 7 days and a remarkable recovery of colorectal mucosa was evident after 14 days of treatment. The amelioration of colon pathology co-existed with a significant decrease of MPO expression, overexpression of iNOS and reduction of nuclear NF-κB p65 in inflammatory cells, and the suppression of apoptosis in colonic epithelial cells.

Conclusion: The simultaneous administration of Mesna and n-3 PUFAs is particularly effective in ameliorating DSS colitis in rats, by reducing oxidative stress, inflammation and apoptosis, probably through a mechanism that involves inhibition of NF-κB and overexpression of iNOS.

Disclosure of Interest: None declared

P0963 A MULTINATIONAL STUDY TO DETERMINE INDICATORS OF SUBOPTIMAL THERAPY AMONG ULCERATIVE COLITIS PATIENTS TREATED WITH TUMOR NECROSIS FACTOR ANTAGONISTS

J. O. Lindsay¹, J. P. Gisbert², R. Mody³, L. Peyrin-Biroulet⁴, A. Armuzzi⁵, B. Bokemeyer⁶, G. C. Nguyen⁷, J. Siebenaler⁸, Ö. Åkerborg⁹, M. Smyth¹⁰

¹Department of Gastroenterology, Barts Health NHS Trust, London, United Kingdom, ²Hospital Universitario de La Princesa, IIS-IP and CIBEREHD, Madrid, Spain, ³Takeda Pharmaceuticals International, Inc., Deerfield, United States, ⁴CHU de Nancy - Hôpital Brabois, Vandœuvre-lès-Nancy, France, ⁵IBD Unit, Complesso Integrato Columbus, Catholic University, Rome, Italy, ⁶Gastroenterology Practice, Minden, Germany, ⁷Mount Sinai Hospital, Toronto, Canada, ⁸Mapi, Milton, United States, ⁹Mapi, Stockholm, Sweden, ¹⁰Takeda Development Centre Europe Ltd, London, United Kingdom

Contact E-mail Address: reema.mody@takeda.com

Introduction: Ulcerative Colitis (UC) patients treated with tumor necrosis factor antagonists (anti-TNFs) may require therapy changes over time, which may be considered as indicators of suboptimal therapy.

Aims & Methods: A multinational, multicentre, retrospective, chart review study was conducted to assess the indicators of suboptimal therapy among adult UC patients receiving their first anti-TNF [infliximab (IFX) or adalimumab (ADA)] between June 2009 and June 2013 (index therapy).

The indicators of suboptimal therapy during 2-year follow up included: anti-TNF dose-escalation (assessed >4 months after index to allow for initial dose adjustments), augmentation with non-biologic therapy, UC-related surgery, discontinuation of first anti-TNF and switching to second anti-TNF. Dose escalation was defined as any increase in either dose, frequency, or both of the index anti-TNF therapy. Augmentation was defined as starting a new non-biologic drug or increase in dose/frequency of the concurrent non-biological drugs with anti-TNF therapy. Discontinuation of index anti-TNF was based on entry in patients’ charts and excluded patients who discontinued anti-TNF because it was effective during the follow-up period. Switch was defined as a subset of discontinuation patients who initiated another anti-TNF therapy over the follow-up period. The number and percentage of patients with each indicator and ≥1 indicator was summarized descriptively by country.

Results: The study included 538 UC patients with mean age (SD) of 41.6 (14.3) years. 47% of patients were females and 73% reported moderate to severe UC at index. The percentages of patients on ADA and IFX as first anti-TNF were 8% and 92% respectively. Overall, within 2 years, 61% of UC patients had ≥1 indicator of suboptimal therapy, 26% had anti-TNF dose escalation, 21% needed augmentation with non-biologic therapy, 9% underwent UC-related surgery and 29% discontinued their index anti-TNF. Of those who discontinued index anti-TNF (N=156), 58% switched to another anti-TNF therapy. Patients with indicators of suboptimal anti-TNF therapy by each country are shown in the table.

Abstract number: P0963 Table. I.

ndicators of suboptimal anti-TNF therapy among UC patients during 2-year follow up

Indicators of suboptimal anti-TNF therapy	Canada	France	Germany	Italy	Spain	UK	Overall
N=51	N=81	N=149	N=132	N=80	N=45	N=538
	% of patients
≥1 of the following Indicators:	70.6	66.7	53.0	59.1	61.3	71.1	61.0
Anti-TNF Dose escalation	39.2	35.8	12.1	33.3	28.8	11.1	25.8
Augmentation with non-biologic therapy	29.4	27.2	20.1	16.7	20.0	17.8	21.0
UC-related Surgery	<5%	8.6	8.1	5.3	10.0	26.7	8.9
Discontinuation of index anti-TNF	35.3	27.2	30.9	22.7	27.5	40.0	29.0
Switching to another anti-TNF	21.6	24.7	18.1	6.8	22.5	13.3	16.9

Conclusion: In this large multinational cohort, more than 60% of UC patients had ≥1 indicator of suboptimal anti-TNF therapy. Predominant indicators included dose escalation and discontinuation of anti-TNF therapy.

STUDY FUNDED BY TAKEDA PHARMACEUTICALS INTERNATIONAL, Inc.

Disclosure of Interest: J. Lindsay Conflict with: Served as a speaker, a consultant and advisory board member for or has received research funding from MSD, Abbvie, Hospira, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Vifor Pharma, Atlantic Health care, Actavis (Warner Chilcott), and Tillotts, J. Gisbert Conflict with: Served as a speaker, a consultant and advisory member for or has received research funding from MSD, Abbvie, Hospira, Kern Pharma, Takeda, Janssen, Pfizer, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Vifor Pharma, R. Mody Conflict with: Employee of Takeda Pharmaceuticals International, Inc., L. Peyrin-Biroulet Lecture fee(s): Abbvie, MSD, Janssen, Takeda, Mitsubishi, Consultancy: Abbvie, MSD, Jansse, Takeda, Hospira, Celltrion, Biogaran, A. Armuzzi Financial support for research: MSD, Lecture fee(s): Abbvie, Astra-Zenaca, Chiesi, Ferring, Hopira, MSD, Otsuka, Takeda, Zambon, Consultancy: Abbvie, Hospira, Liily, MSD, Mundipharma, Pfizer, Sofar, Takeda, B. Bokemeyer Financial support for research: Abbvie, Ferring, UCB, Lecture fee(s): Abbvie, Ferring, MSD, Merckle, Falk, HLR, UCB, Consultancy: Abbvie, MSD, Shire, Ferring, UCB, Hospira, Takeda, Movetis, G. Nguyen Conflict with: Advisory board for Janssen and Abbvie, J. Siebenaler Conflict with: Employee of Mapi, a company hired to conduct the study by Takeda Pharmaceuticals International, Inc., Ö. Åkerborg Conflict with: Employee of Mapi, a company hired to conduct the study by Takeda Pharmaceuticals International, Inc., M. Smyth Conflict with: Employee of Takeda Development Centre Europe Ltd, London, United Kingdom

P0964 LONG-TERM SAFETY OF ADALIMUMAB IN CLINICAL TRIALS IN ADULT PATIENTS WITH CROHN’S DISEASE OR ULCERATIVE COLITIS

J.-F. Colombel¹, R. Panaccione², S. Ghosh², W. J. Sandborn³, P. Rutgeerts⁴, S. Hanauer⁵, G. Van Assche⁴, W. Reinisch⁶, L. Peyrin-Biroulet⁷, A. M. Robinson⁸, W. Lau⁸, B. Huang⁸, B. Pappalardo⁸, H. A. Read⁸

¹Icahn School of Medicine at Mount Sinai, New York, United States, ²University of Calgary, Calgary, Canada, ³University of California at San Diego, La Jolla, United States, ⁴University of Leuven, Leuven, Belgium, ⁵University of Chicago Medical Center, Chicago, United States, ⁶McMaster University, Hamilton, Canada, ⁷Inserm U954 and Department of Gastroenterology, Université de Lorraine, Vandoeuvre-les-Nancy, France, ⁸AbbVie Inc., North Chicago, United States

Introduction: Adalimumab (ADA) is a fully human anti–tumor necrosis factor (TNF) monoclonal antibody used for the treatment of moderate to severe Crohn’s disease (CD) and ulcerative colitis (UC) in patients who have inadequately responded to conventional therapies. Safety from ongoing ADA trials continues to be collected, allowing assessment of long-term safety as the number of patients and the amount of exposure to ADA increase.

Aims & Methods: The aim is to provide an update on the long-term safety profile of ADA in CD and UC patients. Safety data were evaluated for adult patients with CD or UC treated with ADA in randomized, placebo-controlled, phase 3 and 3b trials as well as their open-label extension studies. Treatment-emergent adverse events (AEs) were coded using the Medical Dictionary for Regulatory Activities, version 17.1(2014), and collected from the first dose to up to 70 days after the last dose or through the cutoff date of 31 Dec 2014. AE rates were assessed as events (E) per 100 patient-years (PYs) of exposure to ADA.

Results: As of 31 Dec 2014, the ADA clinical safety database contained data for 3689 CD patients and 1789 UC patients, representing 4178.7 and 3371.9 PYs of ADA exposure, respectively. Overall, AE, SAE, and malignancy rates per PYs exposure were similar between the prior and the most recent data cutoffs for each disease state (Table). The type of infections in the Opportunistic infections (excluding TB) category changed in 2014 resulting in an apparent decreased rate (Table).

Abstract number: P0964 Table 1.

Safety Profile of Adalimumab in Adult CD and UC Patients

AE	All CD Trials as of		All UC Trials as of
	6 Nov 2009 N=3603 PY=4088E (E/100PY)	31 Dec 2014 N=3689 PY=4178.7E (E/100PY)	15 Apr 2012 N=1010 PY=2007E (E/100PY)	31 Dec 2014 N=1789 PY=3371.9E (E/100PY)
Any AE	24.875 (608.4)	25.247 (604.2)	7.508(374.0)	12.281 (364.2)
Serious AE	1473 (36.0)	1521 (36.4)	374 (18.6)	643 (19.1)
AE leading to discontinuation	695 (17.0)	712 (17.0)	235 (11.7)	397 (11.8)
Serious infection	270 (6.6)	281 (6.7)	68 (3.4)	116 (3.4)
Opportunistic infection (excluding TB)*	82 (2.0)*	14 (0.3)	29 (1.4)*	8 (0.2)
Injection site pain	321 (7.9)	322 (7.7)	22 (1.1)	31 (0.9)
Any malignancy	54 (1.3)	50 (1.2)	21 (1.0)	33 (1.0)
AE leading to death	6 (0.1)	6 (0.1)	2 (0.1)	5 (0.1)

*Rates in 2009 and 2012 included events of oral Candidiasis, while rates from 2014 did not.

Conclusion: ADA continues to be well tolerated in patients with moderately to severely active CD and UC. No new safety signals were identified with prolonged ADA use in these patient groups.

Disclosure of Interest: J.-F. Colombel Lecture fee(s): AbbVie, Bristol-Myers Squibb, Ferring Pharmaceuticals, Genentech, Giuliani SPA, Given Imaging, Merck, Millennium Pharmaceuticals, Pfizer, Prometheus Laboratories, Sanofi, Schering-Plough Corporation, Takeda, Teva Pharmaceuticals, and UCB Pharma (formerly Celltech Therapeutics)., Consultancy: AbbVie, Bristol-Myers Squibb, Ferring Pharmaceuticals, Genentech, Giuliani SPA, Given Imaging, Merck, Millennium Pharmaceuticals, Pfizer, Prometheus Laboratories, Sanofi, Schering-Plough Corporation, Takeda, Teva Pharmaceuticals, and UCB Pharma (formerly Celltech Therapeutics)., Conflict with: Advisory board member for AbbVie, Bristol-Myers Squibb, Ferring Pharmaceuticals, Genentech, Giuliani SPA, Given Imaging, Merck, Millennium Pharmaceuticals, Pfizer, Prometheus Laboratories, Sanofi, Schering-Plough Corporation, Takeda, Teva Pharmaceuticals, and UCB Pharma (formerly Celltech Therapeutics)., R. Panaccione Lecture fee(s): AbbVie, Amgen, AstraZeneca, Axcan Pharma (now Aptalis), Biogen Idec, Bristol-Myers Squibb, Centocor, ChemoCentryx, Eisai Medical Research Inc, Elan Pharmaceuticals, Ferring, Genentech, GlaxoSmithKline, Janssen, Merck Sharp & Dohme Corp, Millennium Pharmaceuticals Inc (now Takeda), Ocera Therapeutics Inc, Otsuka America Pharmaceutical, Pfizer, Shire Pharmaceuticals, Prometheus Labs, Schering-Plough, Synta Pharmaceuticals Corp, Teva, UCB Pharma, and Warner Chilcott., Consultancy: AbbVie, Amgen, AstraZeneca, Axcan Pharma (now Aptalis), Biogen Idec, Bristol-Myers Squibb, Centocor, ChemoCentryx, Eisai Medical Research Inc, Elan Pharmaceuticals, Ferring, Genentech, GlaxoSmithKline, Janssen, Merck Sharp & Dohme Corp, Millennium Pharmaceuticals Inc (now Takeda), Ocera Therapeutics Inc, Otsuka America Pharmaceutical, Pfizer, Shire Pharmaceuticals, Prometheus Labs, Schering-Plough, Synta Pharmaceuticals Corp, Teva, UCB Pharma, and Warner Chilcott., S. Ghosh Financial support for research: AbbVie, Consultancy: AbbVie, Shire, Pfizer, Bristol-Myers Squibb, Janssen and Merck & Co, Conflict with: Advisory committee or review panel for AbbVie and Merck & Co., W. Sandborn Financial support for research: AbbVie, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Janssen, Millennium, Novartis, Pfizer, Procter & Gamble Pharmaceuticals, Shire Pharmaceuticals, and UCB Pharma., Lecture fee(s): AbbVie, Bristol-Myers Squibb, and Janssen, Consultancy: AbbVie, ActoGeniX NV, AGI Therapeutics, Inc., Alba Therapeutics Corporation, Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas, Athersys, Inc., Atlantic Healthcare Limited, Aptalis, BioBalance Corporation, Boehringer Ingelheim Inc, Bristol-Myers Squibb, Celgene, Celek Pharmaceuticals, Cellerix SL, Cerimon Pharmaceuticals, ChemoCentryx, CoMentis, Cosmo Technologies, Coronado Biosciences, Cytokine PharmaSciences, Eagle Pharmaceuticals, Eisai Medical Research Inc, Elan Pharmaceuticals, enGene, Inc., Eli Lilly, EnteroMedics, Exagen Diagnostics, Inc., Ferring Pharmaceuticals, Flexion Therapeutics, Inc., Funxional Therapeutics Limited, Genzyme Corporation, Genentech, Gilead Sciences, Given Imaging, GlaxoSmithKline, Human Genome Sciences, Ironwood Pharmaceuticals, Janssen, KaloBios Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Lycera Corporation, Meda Pharmaceuticals, Merck Research Laboratories, Merck Serono, Merck & Co., Millennium, Nisshin Kyorin Pharmaceuticals Co., Ltd., Novo Nordisk A/S, NPS Pharmaceuticals, Optimer Pharmaceuticals, Orexigen Therapeutics, Inc., PDL BioPharma, Pfizer, Procter & Gamble, Prometheus Laboratories, ProtAb Limited, PurGenesis Technologies, Inc., Receptos, Relypsa, Inc., Salient Pharmaceuticals, Salix Pharmaceuticals, Inc., Santarus, Shire Pharmaceuticals, Sigmoid Pharma Limited, Sirtris Pharmaceuticals, Inc. (a GSK company), S.L.A. Pharma (UK) Limited, Targacept, Teva Pharmaceuticals, Therakos, Tillotts Pharma AG, TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics Limited (VBL), and Warner Chilcott UK Limited, P. Rutgeerts Financial support for research: AbbVie, Centocor, MSD, and UCB Pharma, Lecture fee(s): AbbVie, Centocor, MSD, and UCB Pharma, Consultancy: AbbVie, Bristol-Myers Squibb, Centocor, Merck, Takeda, and UCB Pharma, S. Hanauer Financial support for research: AbbVie, Bristol-Myers Squibb, Caremark, Centocor, Elan, McNeal Pharma, Millennium, Novartis, Procter and Gamble and Salix, Consultancy: AbbVie, Bristol-Myers Squibb, Caremark, Centocor, Elan, McNeal Pharma, Millennium, Novartis, Procter and Gamble and Salix, Conflict with: Advisory board member for AbbVie, Bristol-Myers Squibb, Caremark, Centocor, Elan, McNeal Pharma, Millennium, Novartis, Procter and Gamble and Salix, G. Van Assche Financial support for research: AbbVie, Takeda, Janssen, MSD, Genentech, Novartis, Robarts Clinical Trials, and Ferring, Consultancy: AbbVie, Takeda, Janssen, MSD, Genentech, Novartis, Robarts Clinical Trials, and Ferring, Conflict with: Advisory board member for AbbVie, Takeda, Janssen, MSD, Genentech, Novartis, Robarts Clinical Trials, and Ferring, W. Reinisch Financial support for research: Abbott Laboratories, AbbVie, Aesca, Centocor, Falk Pharma GmbH, Immundiagnsotik, and MSD, Lecture fee(s): Abbott Laboratories, AbbVie, Aesca, Aptalis, Centocor, Celltrion, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Immundiagnostik, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka, PDL, Pharmacosmos, Schering-Plough, Shire, Takeda, Therakos, Vifor, Yakult, Consultancy: Abbott Laboratories, AbbVie, Aesca, Amgen, AM Pharma, Astellas, AstraZeneca, Avaxia, Bioclinica, Biogen Idec, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Covance, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Gilead, Grünenthal, ICON, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millennium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestle, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Robarts Clinical Trials, Schering-Plough, Setpointmedical, Takeda, Therakos, Tigenix, UCB, Vifor, Zyngenia, and 4SC, Conflict with: Advisory board member for Abbott Laboratories, AbbVie, Aesca, Amgen, AM Pharma, Astellas, AstraZeneca, Avaxia, Biogen Idec, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Danone Austria, Elan, Ferring, Galapagos, Genentech, Grünenthal, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millennium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestle, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Schering-Plough, Setpointmedical, Takeda, Therakos, Tigenix, UCB, Zyngenia, and 4SC, L. Peyrin-Biroulet Lecture fee(s): AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Ferring, Genentech, Hospira, Janssen, Merck, Mitsubishi, Norgine, Pharmacosmos, Pilège, Shire Pharmaceuticals, Takeda, Therakos, Tillotts Pharma, UCB Pharma and Vifor Pharma, Consultancy: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Ferring, Genentech, Hospira, Janssen, Merck, Mitsubishi, Norgine, Pharmacosmos, Pilège, Shire Pharmaceuticals, Takeda, Therakos, Tillotts Pharma, UCB Pharma and Vifor Pharma, A. Robinson Conflict with: AbbVie employee and may own AbbVie stock and/or options, W. Lau Conflict with: AbbVie employee and may own AbbVie stock and/or options, B. Huang Conflict with: AbbVie employee and may own AbbVie stock and/or options, B. Pappalardo Conflict with: AbbVie employee and may own AbbVie stock and/or options, H. Read Conflict with: AbbVie employee and may own AbbVie stock and/or options

P0965 VALIDITY AND SAFETY OF IRON SUPPLEMENTATION FOR THE TREATMENT OF MODERATE IRON DEFICIENCY ANEMIA IN PATIENTS WITH CROHN`S DISEASE—A RANDOMIZED, CONTROLLED, OPEN-LABEL, SINGLE CENTER STUDY

J. Tang¹, X. Gao¹, M. Zhi¹, P. Hu¹

¹Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, GuangZhou, China

Contact E-mail Address: tangjiansys@163.com

Introduction: The necessity and optimal route for iron supplementation to improve anemia in Crohn`s disease (CD) has not been determined so far. We therefore performed a randomized, controlled, open label, single center study to evaluate the necessity, efficacy and safety of iron supplementation for the treatment of iron deficiency anemia (IDA) in patients with CD.

Aims & Methods: 49 patients with moderate anemia(hemoglobin(Hb):60-90g/l), transferrin saturation ≤ 20% and/or serum ferritin concentrations ≤ 20µg/L were enrolled in this study. All patients were divided into three groups. Intravenous group received iron sucrose injection of 200 mg two or three times per wk until reached a total dose according to Ganzoni’s Formula. Oral group received polysaccharide iron complex 150 mg per day for 12 wks. The other patients didn`t received any iron supplementation. Response to anemia therapy was defined as Hgb ≥ 110 g/L in women, Hgb ≥ 120 g/L in men and/or Hgb rise ≥ 20g/l.

Results: 47 patients completed the study while 2 patients quitted because of surgery. At 12wks, Hgb and response rate (RR) of intravenous group (Hgb: 110.2 ± 16.2g/l, RR: 75.0%(15/20)) were superior to oral group (Hgb: 101.9 ± 17.9g/l, RR: 54.5% (6/11)) and no iron supplement group (Hgb: 99.1 ±15.7g/l, RR: 25%(4/16)) (P=0.02, P<0.01). No matter received iron supplement therapy or not, Hgb in patients in remission (CDAI < 150) was remarkable higher than in patient in active phase at 12wks (101.0 ± 6.2g/l vs 81.0 ± 12.5g/l, t=-2.2, P=0.03). Multiple logistic analysis showed that no iron supplement, active disease, complication were independent risk factors for no response to anemia therapy. 3 patient in oral group could not tolerate side effects and re-divided into intravenous group. However, no statistical difference on side effect was found between intravenous and oral group.

Conclusion: Iron supplementation therapy could significantly improve IDA in CD. Intravenous therapy was more effective than oral supplement. Iron supplementation will be more effective when disease activity under control.

Disclosure of Interest: None declared

P0966 ANTIBODIES TO INFLIXIMAB, BODY WEIGHT AND LOW SERUM ALBUMIN LEVELS INCREASE CLEARANCE OF INFLIXIMAB, A POPULATION PHARMACOKINETIC STUDY IN 332 IBD PATIENTS

J. F. Brandse¹, D. R. Mould², Y. Ashruf¹, O. Smeekes¹, G. R. van den Brink¹, G. R. D'Haens¹

¹Department of Gastroenterology & Hepatology, Academic Medical Center, Amsterdam, Amsterdam, Netherlands, ²Projections Research Inc, Phoenixville, United States

Contact E-mail Address: j.f.brandse@amc.uva.nl

Introduction: Factors suggested to influence the pharmacokinetics (PK) of infliximab (IFX) in patients with inflammatory bowel disease (IBD) have mainly been derived from clinical trials or computer modelling, clinical data are scarce.

Aims & Methods: We aimed to study the real-life PK of IFX in a large cohort of IBD patients and to identify patient, disease and treatment characteristics that influence serum concentrations and clearance of IFX. All measurements (November 2004 - August 2014) of IFX serum concentrations in IBD patients collected at a tertiary referral center were identified. Medical charts of these patients were reviewed for patient, disease and treatment characteristics (gender, age, body weight, location and behaviour of disease, dose, co-immunomodulators, serum albumin, CRP). IFX serum concentrations and antibodies to IFX (ATI) were measured using an ELISA and antigen binding test (radioimmunoassay, Sanquin Laboratories, Amsterdam, The Netherlands). PK was analysed by nonlinear mixed-effects modelling and described using a 2-compartiment PK model. All influential covariates were combined into a full model.

Results: A total of 997 distinct IFX concentrations measurements were included, comprising data from 332 IBD patients (54% male, mean age 39 years, 3 measurements/patient). Disease extent was scored by the Montreal classification for 253 Crohn’s disease patients (L1: 55/253, L2: 80/253, L3: 118/253) and 79 ulcerative colitis patients (E1: 6/79, E2: 30/79, E3: 43/79). 264/332 (80%) of patients were anti-TNF naïve at start of IFX and 144/332 (43%) were receiving concomitant immunomodulation, with a mean IFX dose of 5.2 mg/kg, at time of measurement. ATIs were detected in 75/332 (23%) patients, resulting in unmeasurable serum IFX concentrations in 83% of their samples. All samples with ATI titers higher than 30 AU/mL were associated with unmeasurable IFX concentrations. The mean (inter individual variability) values for clearance, central and peripheral volume of distribution were 0.38 L/day (50%), 5.07 L (30%) and 3.59 L (32%). PK characteristics were similar for Crohn’s disease and ulcerative colitis. The presence of ATIs, low body weight and serum albumin were identified as covariates independently (P < 0.001) affecting clearance. The presence of ATIs corresponded with an mean (SE) 4.40 (11.1) fold increased clearance. For body weight, range from 50 to 120kg resulted in a 1.31 fold increase over a 2.4 fold weight increase. Serum albumin had a -1.65 (8.4) fold inverse impact on clearance. Because serum CRP values tended to change rapidly after initiation of treatment, and use of concomitant immunomodulators was often intermittent, these factors could not be evaluated as independent covariates although the administration of continuous concomitant immunomodulators was associated with a decrease in clearance. Line of treatment was predictive of clearance, with anti-TNF naive patients exhibiting lower clearance than the previously exposed patients.

Conclusion: Antibodies to infliximab, low body weight and low serum albumin levels increase clearance of infliximab.

Disclosure of Interest: J. Brandse Lecture fee(s): MSD, Abbvie, Takeda, D. Mould: None declared, Y. Ashruf: None declared, O. Smeekes: None declared, G. van den Brink: None declared, G. D'Haens: None declared

P0967 COMPARATIVE STRUCTURAL, FUNCTIONAL, NONCLINICAL, AND PHASE 1 SIMILARITY ASSESSMENTS OF PF-06438179, A POTENTIAL BIOSIMILAR TO INFLIXIMAB, AND MARKETED REFERENCE PRODUCTS

J. E. McClellan¹, C. Udata², D. Yin², S. Salts², T. R. Johnson², M. Derzi³, M. Bolt³, H. D. Conlon³, C. F. Kirchhoff⁴, L. G. Lorello⁵, J. McNally³, M. I. Rehman⁶

¹Pfizer Inc., New York, NY, ²Pfizer Inc., San Diego, CA, ³Pfizer Inc., Andover, MA, ⁴Pfizer Inc., Chesterfield, MO, ⁵Pfizer Inc., Groton, CT, ⁶Pfizer Inc., Cambridge, MA, United States

Introduction: PF-06438179 is being developed as a potential biosimilar to Remicade^® (infliximab), which is a chimeric mouse/human monoclonal antibody that binds to the tumour necrosis factor (TNF) protein, in a stepwise approach following globally accepted regulatory guidelines. The similarity of PF-06438179 to infliximab reference products sourced from the United States (infliximab-US) and from the European Union (infliximab-EU) was assessed in structural, functional, in vivo nonclinical pharmacokinetic (PK)/tolerability and clinical PK studies.

Aims & Methods: Structural similarity was assessed using chromatographic peptide mapping. Functional similarity was assessed in vitro using an inhibition of soluble TNF-induced cell apoptosis assay. PK, tolerability and anti-drug antibody (ADA) response were evaluated in rats administered a single IV dose (0, 10 or 50 mg/kg) of PF06438179 or infliximab-EU. In a phase 1 study (NCT01844804), 146 healthy volunteers received a single 10 mg/kg IV dose of PF06438179 (n=49), infliximab-US (n=48), or infliximabEU (n=49). All subjects provided informed consent. PK was evaluated over 8 weeks; safety and ADA were assessed up to 12 weeks. PK similarity in humans was considered to be demonstrated if the 90% confidence interval (CI) of the test-to-reference ratio of maximum concentration (C_max) and area under the concentration time curve (AUC) were within the 80.00%–125.00% bioequivalence (BE) acceptance window.

Results: Peptide mapping showed superimposable chromatographic profiles of PF-06438179, infliximab-US and infliximab-EU, demonstrating structural similarity. The dose-response curves of inhibition of cell apoptosis induced by all three study drugs were also superimposable, demonstrating functional similarity. In rats, PF-06438179 and infliximabEU were well-tolerated. Systemic exposures (assessed by C_max and AUC) in dosed animals appeared similar, with mean exposure ratios of PF06438179 relative to infliximab-EU ranging from 0.88 to 1.16. None of the rats developed detectable levels of ADA following administration of PF06438179. In healthy volunteers, the three study drugs exhibited a similar PK profile, and the 90% CI for the ratios of C_max and AUC were within the BE acceptance window of 80.00%–125.00% for each, individual three-way comparison. Overall safety and ADA profiles were comparable among the treatment groups.

Conclusion: Comparative studies demonstrated structural, functional, and nonclinical and clinical PK profiles of PF-06438179 to be similar to infliximab-US and/or infliximab-EU. A global, comparative clinical study is ongoing to assess efficacy and safety of PF06438179 and infliximab-EU in combination with methotrexate in subjects with active rheumatoid arthritis.

Disclosure of Interest: J. McClellan Shareholder: Pfizer Inc, Conflict with: Employee of Pfizer Inc, C. Udata Shareholder: Pfizer Inc, Conflict with: Employee of Pfizer Inc, D. Yin Shareholder: Pfizer Inc, Conflict with: Employee of Pfizer Inc, S. Salts Shareholder: Pfizer Inc, Conflict with: Employee of Pfizer Inc, T. Johnson Shareholder: Pfizer Inc, Conflict with: Employee of Pfizer Inc, M. Derzi Shareholder: Pfizer Inc, Conflict with: Employee of Pfizer Inc, M. Bolt Shareholder: Pfizer Inc, Conflict with: Employee of Pfizer Inc, H. Conlon Shareholder: Pfizer Inc, Conflict with: Employee of Pfizer Inc, C. Kirchhoff Shareholder: Pfizer Inc, Conflict with: Employee of Pfizer Inc, L. Lorello Shareholder: Pfizer Inc, Conflict with: Employee of Pfizer Inc, J. McNally Shareholder: Pfizer Inc, Conflict with: Employee of Pfizer Inc, M. Rehman Shareholder: Pfizer Inc, Conflict with: Employee of Pfizer Inc

P0969 STW 5, A MULTI-COMPONENT HERBAL PREPARATION, MODERATES MOTILITY AND INFLAMMATION CHALLENGES IN THE ENTERIC NERVOUS SYSTEM (ENS)

K.-H. Schäfer¹, D. Grundmann¹, M. Klotz¹, H. Rabe¹, H. Abdel-Aziz², O. Kelber²

¹University of Applied Sciences Kaiserslautern, Zweibrücken, ²Steigerwald GmbH, Darmstadt, Germany

Contact E-mail Address: karl-herbert.schaefer@hs-kl.de

Introduction: The enteric nervous system is responsible for the undisturbed regulation of gut motiliy, secretion or resorption. Whenever the gastrointestinal tract is affect by diseases, the ENS is also part of the problem. Especially during inflammation, the ENS can be stimulated and challenged by inflammatory signaling molecules such as cytokines or hormones.

Aims & Methods: respectively the enteric nervous system. Gut segments were kept in an organ bath under perfusion conditions and motility increased by neostigmin application. STW-5 was added after the stimulation. To investigate whether the ENS was the target for the compound, we also performed electrophysiological measurements of enteric neuronal networks on microelectrode arrays.

Inflammation was simulated in isolated ENS tissue. Myenteric plexus from adult mice from both jejunum and colon was isolated and either stimulated with a cytokine cocktail of Interferon-gamma, IL-1ß and TNF-alpha alone, or in combination with the multi-component herbal preparation STW-5.

The plexus tissues were kept for 24 hrs in tissue culture medium and supernatant was collected the following day. Cytokine liberation was measured using Multiplex-ELISA.

Results: The application of STW-5 reduced significantly the neostigmin-induced motility in a dose dependent manner. The electrical activity of the neuronal networks could also be increased by neostigmine and was reduced to basal activity by additional STW-5. In the inflammation approach, the supernatants from colonic and jejunal myenteric plexus showed different responses. While many cytokines were released after cytokine stimulation in both colonic and jejunal preparations, STW led to a complete downregulation of the release only in the colonic myenteric plexus.

Conclusion: The application of STW-5 reduced significantly the neostigmin-induced motility in a dose dependent manner. The electrical activity of the neuronal networks could also be increased by neostigmine and was reduced to basal activity by additional STW-5. In the inflammation approach, the supernatants from colonic and jejunal myenteric plexus showed different responses. While many cytokines were released after cytokine stimulation in both colonic and jejunal preparations, STW led to a complete downregulation of the release only in the colonic myenteric plexus.

Disclosure of Interest: K.-H. Schäfer Financial support for research: Study payed by Steigerwald, D. Grundmann: None declared, M. Klotz: None declared, H. Rabe: None declared, H. Abdel-Aziz Conflict with: payed by Steigerwald, O. Kelber Conflict with: payed by Steigerwald

P0970 BIOSIMILAR INFLIXIMAB: EFFICACY AND SAFETY BASED ON INTERIM RESULTS FROM A PROSPECTIVE NATIONWIDE COHORT

K. B. Gecse¹, K. Farkas², B. Lovász¹, J. Banai³, L. Bene⁴, B. Gasztonyi⁵, P. A. Golovics¹, T. Kristof⁶, L. Lakatos⁷, P. Miheller⁸, F. Nagy², K. Palatka⁹, M. Papp⁹, Á. Patai¹⁰, Á. Salamon¹¹, T. Szamosi³, Z. Szepes², T. G. Tóth¹², Á. Vincze¹³, T. Molnár², P. Lakatos¹

¹First Department of Medicine, Semmelweis University, Budapest, ²First Department of Medicine, University of Szeged, Szeged, ³Department of Gastroenterology, Military Hospital – State Health Centre, ⁴First Department of Medicine, Peterfy Hospital, Budapest, ⁵Second Department of Medicine, Zala County Hospital, Zalaegerszeg, ⁶Second Department of Medicine, BAZ County Hospital, Miskolc, ⁷Department of Medicine, Csolnoky Ferenc Regional Hospital, Veszprem, ⁸Second Department of Medicine, Semmelweis University, Budapest, ⁹Department of Gastroenterology, University of Debrecen, Debrecen, ¹⁰Department of Medicine, Markusovszky Hospital, Szombathely, ¹¹Department of Gastroenterology, Tolna County Teaching Hospital, Szekszárd, ¹²Department of Gastroenterology, János Hospital, Budapest, ¹³First Department of Medicine, University of Pécs, Pécs, Hungary

Contact E-mail Address: krisztina.gecse@gmail.com

Introduction: Biosimilar infliximab CT-P13 received EMA approval in June 2013 for all indications of the originator product. Prospective data on the efficacy and safety of the biosimilar infliximab in IBD are lacking.

Aims & Methods: A prospective, nationwide, multicentre, observational cohort was designed to examine the efficacy and safety of CT-P13 infliximab biosimilar in the induction treatment of Crohn’s disease (CD) and ulcerative colitis (UC). Demographic data were collected and a harmonized monitoring strategy was applied. Early clinical remission, response and early biochemical response was evaluated at week 14. None of the patients had received infliximab within 12 months prior to initiation of the biosimilar infliximab. Safety data was registered.

Results: 201 consecutive IBD patients (122 CD patients and 79 UC patients) were included in the present cohort. The age at disease onset was 24/29 years (median, IQR: 19-35 and 22-38) in CD and UC patients, respectively. 38/43% of CD patients had colonic/ileocolonic disease localization, 34% of patients had perianal disease and 26% of the patients had gone through previous surgery. 5/38/57% of UC patients had proctitis/left-sided colitis/extensive colitis. 27/19% of patients had received previous anti-TNF therapy in CD and UC, respectively. 60/58% of CD/UC patients received concomitant immunosuppressives at baseline. 54/82% and 61%/90% of the CD (n=94/64) patients and 72%/77% and 65%/80% of the UC (n=60/40) patients reached clinical remission/response by week 6 and 14. There was no significant difference in the remission and response rates between patients with or without previous anti-TNF exposure. Additionally, there was a decrease in biomarkers by week 14 (mean CRP level decreased from 20.8 mg/L to W6: 11.4mg/L and W14: 6.7mg/L in CD and from 32.1mg/L to W6: 11.2mg/L and W14: 9.9 mg/L in UC). 8 patients had allergic reactions, 8 patients infections and 1 death occurred.

Conclusion: This prospective nationwide cohort shows that CT-P13 is safe and effective in the induction of clinical remission and response in both CD and UC.

Disclosure of Interest: None declared

P0971 INFLIXIMAB AND ADALIMUMAB IN CROHN'S DISEASE: A COMPARATIVE ANALYSIS OF EFFICACY, SAFETY AND MANAGEMENT OF SECONDARY LOSS OF RESPONSE IN A COHORT ROMANIAN STUDY

L. E. Fulger¹, C. M. Preda¹, L. Gheorghe¹, C. Gheorghe¹, A. Goldis², A. Trifan³, M. Tantau⁴, L. Negreanu⁵, C. Tieranu¹, C. Meianu¹, M. Diculescu¹

¹Gastroenterology and Hepatology, Clinical Institute Fundeni, Bucharest, ²Gastroenterology and Hepatology, Clinic of Gastroenterology, Timisoara, ³Gastroenterology and Hepatology, Clinic County Hospital “Sf. Spiridon”, Iasi, ⁴Gastroenterology and Hepatology, Regional Institute of Gastroenterology and Hepatology “O. Fodor”, Cluj, ⁵Gastroenterology and Hepatology, Clinic Universitary Emergency Hospital, Bucharest, Romania

Contact E-mail Address: larisa@bum-internet.ro

Introduction: Adalimumab(ADA) and Infliximab(IFX), are an effective induction and maintenance therapy for moderate to severe Crohn’s disease. The aim of this study was to evaluate their efficacy in a large Romanian population and to identify predictor factors of response.

Aims & Methods: We performed a national retrospective cohort study including 265 patients (136 ADA, 129 IFX) between 2008 and 2014, all naive to biologics. Binary logistic regression was performed with the statistical program Minitab, to identify predictors of response.

Results: Patients were half women, with a median age of 36 years, a median disease duration of 2.5 years, most of them (80%) received Azathioprine before biologic therapy, 70% aged 17- 40 years at diagnosis, almost 50% with ileocolonic involvement, 60% non-obstructive non-fistulising disease, and 20% suffered surgery (intestinal resection) before the biologic therapy. Mean therapy duration was 20 months in ADA group and 36 months in IFX group. 67% of patients had moderate flare of the disease, while 16% had mild disease activity. Complete response to ADA was recorded in 77%, secondary loss of response in 18%, while to IFX the rate of complete response was 65%, and secondary loss of response 28%, statistically comparable. With most patients with secondary loss of response to ADA (79.2%), the dose was escaladated, which reinduced response in 84.2%. 12.5% were switched to Infliximab, with a significantly lower rate of response: 33%. In 26/37 (70%) patients that lost response to IFX, the dose was increased, which resulted in regaining response in approximately 40% of patients. 12/38 subjects (30%) were switched to Adalimumab, with a better result: 83% regained response. Regarding surgical interventions, 74.5% of resected patients achieved complete response, comparable to non-resected patients (70%). Secondary loss of response was found in 20% of resected patients compared to 24.5% of the non-resected, while primary non-response was recorded in 4% versus 2%. 9 of the 23 resected patients treated with IFX suffered re-resection for POR, compared to 4 of the 28 treated with ADA, but p-value was not statistically significant 0.16. 13 of 216 non-resected subjects suffered surgical interventions on biologic therapy (6%).

Predictors of loss of response to ADA were: severe disease (CDAI >450): OR 5.67 ( 95% CI 0.17,185.65), presence of perianal fistulae: OR 5.87(95% CI 0.26,131.15), fistulising disease OR 3.71( 95% CI 0.18,73.72). Predictors of loss of response to IFX were: age > 40y: OR 63.71(95% CI 2.93, 1384.62), severe disease: OR 8.25 (95%CI 0.38,177.8), perianal fistulae OR 3.71 ( 95% CI0.65, 30.63).

Conclusion: In a real-life cohort, Adalimumab and Infliximab are equally effective in Crohn’s disease, with a complete response rate of ∼70%. Predictors of poor response to biologics were: severe active disease, perianal disease and fistulising behaviour. In case of secondary loss of response to IFX, the best solution is to switch to ADA, with 83% chance of regaining response, while in case of secondary loss of response to ADA, increasing the dose leads to 84 % chance of regaining response.

Disclosure of Interest: None declared

P0972 A REAL WORD REVIEW OF PATIENT COMORBIDITIES IN CROHN’S DISEASE AND THEIR IMPACT ON TREATMENT STRATEGIES AND PATIENT OUTCOMES

L. Chanroux¹, J. Casellas¹

¹Research Partnership, London, United Kingdom

Contact E-mail Address: laurentc@researchpartnership.com

Introduction: Several studies have evaluated the increased prevalence of comorbid diseases and risk factors in Crohn’s disease (CD) patients and understanding the overlapping pathogenesis of comorbidities may be key to effectively managing and treating those with this complex disorder.

Aims & Methods: We used patient data collected as part of an online treatment survey conducted among a panel of gastroenterologists between April 2010 and December 2013 in France, Germany, Italy, Spain and the UK. We analysed 11,730 records of patients suffering from moderate to severe CD and classified them according to their comorbidities into 4 groups. Group 1 patients were reported as suffering from no comorbid conditions; group 2 patients suffered from cardiovascular or metabolic comorbidities including hypertension, metabolic syndrome and diabetes (CVD); group 3 consisted of patients who suffered from anxiety and/or depression and group 4 included all patients with an autoimmune disease, including rheumatoid arthritis, psoriasis, ulcerative colitis, uveitis and multiple sclerosis.

Results: Patients with CVD were on average significantly older than those from the other groups (50 years, p < 0.05). They were also significantly heavier (74kg) and more likely to be male (62% of patients). These patients had a greater number of comorbidities (1.3) and had been diagnosed for longer (9 years). They were more likely to have moderate CD at diagnosis but had the lowest level of biologic use (53%) with the greatest delay from diagnosis to 1^st ever biologic (7 years).

Patient suffering from depression/anxiety were significantly more likely to currently have moderate or severe CD (46% and 17%, respectively) and more commonly suffered from fistulising disease (29%). A greater proportion of these patients were currently experiencing fistulae (33%) and had their upper GI tract (5%), rectum (26%) and anus (21%) affected by their disease vs. other groups. They reported the highest average CDAI score (167) and the highest proportion of patients having undergone ≥ 3 surgical interventions for their disease (5%). Rapid disease progression (55%) and frequency of relapse (26%) were more frequently chosen as reasons for initiating biologics among these patients.

Patient with autoimmune comorbidities were most likely to be receiving anti-inflammatories (13%) and biologics (72%) with the latter more commonly chosen due to patients’ extra intestinal manifestations (46%). Although this group reported the highest proportion of patients having experienced remission over the course of their disease (45%) there were no significant differences in the frequency or duration of remission between the groups.

We saw no clear correlation between biologic use and improved patient outcomes and little correlation between individual disease attributes and patients' psychological status.

Conclusion: Our data confirm that CD is a heterogeneous disease with clear differences in patient profiles across the main comorbidity groups we covered. These differences appear to lead to different treatment approaches which in turn may lead to varying patient outcomes. Our results do not show a correlation between biologic therapy and patient outcomes but suggest that patients with uncontrolled disease (flaring, fistulae and high CDAI) are more likely to suffer from depression and anxiety, highlighting the impact that tight disease control can have on patients’ quality of life.

Disclosure of Interest: None declared

P0973 IDENTIFICATION OF A CUT-OFF FOR PERSISTENT ANTI-INFLIXIMAB ANTIBODIES AS A PREDICTOR OF RESPONSE TO INFLIXIMAB MONOTHERAPY

L. Del Nero¹, G. Bodini¹, E. Giannini¹, V. Savarino¹, C. De Maria¹, I. Baldissarro¹, A. Jain², E. Savarino³

¹Internal medicine, IRCCS San Martino, Genoa, Italy, ²Research and Development, Prometheus Laboratories, San Diego, United States, ³Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy

Introduction: The clinical and predictive role of anti-Infliximab antibodies (AIA) presence and concentration are still debated, both in Crohn’s disease (CD) and ulcerative colitis (UC) patients. However, there is increasing evidence of their usefulness in order to improve the management of patients on biological treatment who experience a loss of response (LOR). AIA can be subdivided into 2 types, persistent and transient, on the basis of their occurrence on multiple samples and capability of interfering with infliximab trough levels (TL), and therefore persistent AIA seem to play a major role on treatment outcome.

Aims & Methods: The aim of our retrospective study was to evaluate the clinical relevance of persistent AIA in a single-center cohort of inflammatory bowel disease (IBD) patients. We selected from our cohort of 56 IBD patients treated with IFX mono-therapy who achieved clinical and biochemical remission after induction (IFX schedule: 5 mg/kg at week 0, week 2, and week 6), 18 patients (32.1%) who developed persistent AIA during 48 weeks follow-up. Blood samples were drawn at standardized time points (i.e., baseline, 2 weeks, 6 weeks, and every 8 weeks) before IFX infusion. TL and AIA were measured using an homogenous mobility shift assay (HMSA; Prometheus Lab, San Diego, United States). Clinical disease activity was assessed both at week 14 (i.e. after induction) and week 48 by the Harvey-Bradshaw Index (HBI, remission defined by HBI < 5) in CD patients and by the Mayo score for UC patients (remission defined by Mayo score <2). Also, protein-C reactive and erythrocyte sedimentation rate (ESR) were measured.

Results: Eighteen patients (11 CD and 7 UC, 10M/8F, median age 39.5 years, range 18-69) developed persistent AIA at a median of 2 weeks during 48 weeks follow-up. Among these patients, 12 (66.7%) experienced LOR during the follow-up period. Median AIA were significantly higher in patients who showed LOR as compared to patients who maintained remission (8.29 U/ml, range 0.62-30.52 U/ml, versus 1.41 U/ml, range 0.77-9.94 U/ml; P=0.04). ROC curve identified a persistent AIA cut-off of 3.91 U/mL as the threshold with the highest accuracy for the identification of relapsers (AUROC=0.799, specificity=75.0%, sensitivity=83.3%).

Conclusion: The early occurrence of elevated persistent AIA serum concentrations during IFX mono-therapy treatment is associated with high risk of LOR. Furthermore, the use of an AIA concentration cut-off of 3.91 U/mL can be useful to accurately identify patients with LOR, although these results need to be confirmed in larger series.

Disclosure of Interest: None declared

P0974 ANTI-TNF THERAPY IN ULCERATIVE COLITIS. SHOULD WE REMOVE 5-ASA?

M. Barreiro-De Acosta¹, I. Baston¹, D. De la Iglesia¹, R. Ferreiro¹, A. Lorenzo¹, J. E. Dominguez-Muñoz¹

¹Gastroenterology, University Hospital, Santiago, Spain

Contact E-mail Address: manubarreiro@hotmail.com

Introduction: 5-aminosalicylates (5-ASA) are effective drugs for induction and maintenance treatment in ulcerative colitis (UC) patients. However, their usefulness as concomitant treatment with Anti-TNF drugs remains uncertain.

Aims & Methods: The aim of this study was to evaluate the efficacy of this therapeutic combination in patients with moderate to severe UC. Methods: A retrospective observational single-centre study was designed. Inclusion criteria were all moderate to severe UC patients that were treated with anti-TNF drugs (Infliximab or Adalimumab) between January 2007 and December 2013. Only anti-TNF naïve patients were included. Patients with pouchitis or having received previous anti-TNF treatment were excluded. Clinical and demographic characteristics were recorded as well as the number of months in which all patients were treated with anti-TNF agents. Efficacy was defined as sustained remission and measured as the duration of clinical remission in months until treatment failure (defined as the need for intensification, a switch to another anti-TNF or colectomy). The presence of significant adverse events was also evaluated. The concomitant use of 5-ASA was also assessed. The data is shown as percentages and Hazard Ratio after Cox regression analysis was performed.

Results: 55 patients were consecutively included. 31 women (56.3%) and 24 men (44.7%) with a mean age of 44.2 years. 49 patients started treatment with Infliximab (89.1%) and 6 with Adalimumab (10.9%). Regarding smoking habits, only 1 patient was smoker (1.8%) and 6 were former smokers (10.9%). 25 patients received concomitant treatment with 5-ASA (45.4%) and 30 patients received concomitant treatment with azathioprine (54.5%). Treatment failure was observed in 26 patients (47.3%), those of which 19 needed treatment intensification (73.1%). The average time of sustained clinical remission was 10.1 months, being higher in women (14.5 months) than in men (4.9 months). Regarding 5-ASA concomitant therapy, despite the fact that patients with 5-ASA maintained remission for more time (12 months) than those without 5-ASA (8.4 months), statistically significant differences were not discovered. 3 patients (5.4%) presented adverse events and had to be withdrawn from treatment, all of whom were not receiving concomitant 5-ASA. After multivariable analysis the only factor independently associated with maintaining remission was female gender HR 4.33 (95% CI, 1.35 to 13.90). No perceptible influence of concomitant treatment with 5-ASA was found.

Conclusion: Roughly half of patients with UC maintained remission with anti-TNF therapy. The concomitant use of 5-ASA did not have any influence in maintaining remission in patients with moderate to severe UC. Female gender was associated with higher rate of response in this study.

Disclosure of Interest: None declared

P0975 FACTORS ASSOCIATED WITH ANTI-TNF THERAPY FAILURE IN PATIENTS WITH CROHN’S DISEASE (CD). DOES THE TYPE OF DRUG HAVE ANY INFLUENCE?

M. Barreiro-De Acosta¹, I. Baston¹, D. De la Iglesia¹, R. Ferreiro¹, A. Lorenzo¹, J. Dominguez-Munoz¹

¹Gastroenterology, University Hospital, Santiago, Spain

Contact E-mail Address: manubarreiro@hotmail.com

Introduction: Anti-TNF monoclonal antibodies are effective drugs for induction and maintenance of remission in Crohn's disease (CD). However a significant portion of patients do not respond or lose the response during the treatment and predictive factors are not well known. There is no direct data comparing the efficacy between different anti-TNF drugs.

Aims & Methods: The aim of this study was to evaluate the factors associated with anti-TNF therapy failure in Anti-TNF naive patients with CD. Methods: A retrospective, observational single-centre study was designed. Inclusion criteria were all naïve patients older than 17 years old who started treatment with anti-TNF drugs, either Infliximab or Adalimumab, for moderate to severe CD between January 2007 and December 2013. Patients who had been previously treated with another anti-TNF were excluded. Patients who started anti-TNF for different indications like prevention of recurrence or refractory extraintestinal manifestations, were not included. Treatment failure was defined as the need for dose intensification due to loss of response, surgery resection, or therapy removal for ineffectiveness. The influence of demographic and clinical variables (gender, age, smoking history and type of biological agent used) on treatment failure was also evaluated. Results are shown as OR and95% CI and analyzed by the Chi square test and multivariable logistic regression analysis.

Results: 129 CD patients were consecutively included: 72 women (55.8%) and 57 men (44.2%) with a mean age of 35.9 years. 64 treatments with Infliximab (49.6%) and 65(50.4%) with Adalimumab. 52 smokers (40.3%) and 12 former smokers (9.3%). Mean Treatment failure was observed in 51 patients (39.5%): 36 due to dose intensification (27.9%), 11 due to surgery (8.5%) and 4 primary failures after anti TNF induction therapy (3.1%). No factors associated with treatment failure were identified in the multivariant analysis. Similar rates of treatment failure were found between infliximab and adalimumab(p = 0.802).

Conclusion: More than 60% of CD patients maintained response to anti-TNF therapy, and 27% of patients required treatment intensification. No differences were found between Infliximab and Adalimumab in terms of treatment failure in patients with CD.

Disclosure of Interest: None declared

P0976 PROSPECTIVE, RANDOMIZED CLINICAL TRIAL COMPARING THE EFFICACY OF TWO VACCINES AGAINST HEPATITIS B VIRUS (HBV) IN INFLAMMATORY BOWEL DISEASE (IBD) PATIENTS

M. Chaparro ^1,2, J. Gordillo³, E. Domènech^4,5, M. Esteve⁶, M. Barreiro de-Acosta⁷, A. Villoria^8,9, E. Iglesias-Flores¹⁰, M. Blasi¹¹, J. E. Naves¹², O. Benítez^13,14, L. Nieto⁷, X. Calvet^8,9, V. García-Sánchez¹⁰, J. R. Villagrasa¹, A. C. Marín^1,15, M. Ramas^1,15, I. Moreno¹, J. P. Gisbert¹, on behalf of Gastroenterology Units

¹Hospital Universitario de La Princesa, ²CIBERehd and IIS-IP, Madrid, ³Hospital Santa Creu i Sant Pau, ⁴Hospital Germans Trias i Pujol, ⁵CIBERehd, Barcelona, ⁶Mutua de Terrassa, Terrassa, ⁷Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, ⁸Hospital de Sabadell, ⁹CIBERehd, Sabadell, ¹⁰Hospital Universitario Reina Sofía, Córdoba, ¹¹Gastroenterology Unit, Hospital Santa Creu i Sant Pau, Barcelona, ¹²Hospital Germans Trias i Pujol, Badalona, ¹³Gastroenterology Unit, Mutua de Terrassa, ¹⁴CIBERehd, Terrassa, ¹⁵CIBERehd, Madrid, Spain

Contact E-mail Address: mariachs2005@gmail.com

Introduction: .

Aims & Methods: To compare the success rate between 2 HBV vaccines in IBD patients: the traditional (Engerix^®) and a new vaccine with an adjuvant (Fendrix^®). To identify predictive factors of response to the vaccine

IBD patients with negative HBV serology and without previous vaccination against HBV were included (EUDRA CT number: 2010-023947-14), and randomized 1:1 to receive Fendrix^® or double doses of Engerix^® at months 0, 1, 2 and 6. Anti-HBs concentration was measured 2 months after the 3^rd and 4^th vaccine doses

Results: 173 patients were included. 54% of patients received Engerix^® and 46% Fendrix^®. Overall, 43% of patients had response (pre-defined as anti-HBs ≥ 100 IU/L) after the first 3 doses (165 patients have received 3 doses up to now), and 71% after the completion of the vaccination (161 have completed the vaccination). 47% of patients that did not respond after the 3^th dose, responded to the 4^th vaccine administration (p < 0.0001). The response rate after the 4 doses was 75% (95%CI, 63-84%) with Fendrix^® vs. 67% (56-77%) with Engerix^® (p=0.3; however, the statistical power for this comparison was only 30%); considering anti-HBs³10 IU/L (the standard threshold to define response), the success rate was marginally higher with Fendrix^® than with Engerix^® (88% [78-94%) vs. 77% [66-85%], p=0.06). In patients under anti-TNF treatment, the response rate (anti-HBs³100 IU/L) after the 4 doses was 67% (47-83%) with Fendrix^® vs. 45% (27-64%) with Engerix^® (p=0.09); and considering anti-HBs³10 IU/l, the success rate was 80% (61-82%) with Fendrix^® and 58% (39-75%) with Engerix^® (p=0.06). In the multivariate analysis, older age (OR=0.9, p < 0.0001), and the treatment with immunosuppressants (OR=0.12, p < 0.01) or anti-TNFs (OR=0.09, p < 0.0001) were associated with a lower response rate to the vaccination. The type of vaccine ¾Engerix^® or Fendrix^®¾ was not associated with the response to the vaccination (OR=1.8, 95%CI=0.8-4). The frequencies of IBD relapses during the study period were similar in patients receiving Fendrix^® and Engerix^® (17% vs. 22%)

Conclusion: We could not demonstrate a statistically significant higher response rate of Fendrix^® (conventional dose) over Engerix^® (double dose) in IBD patients, although a beta error cannot be excluded. A 4-dose vaccine schedule significantly increases the response compared with a 3-dose regimen. Older age and immunosuppressive and anti-TNF treatment impaired the success rate of the vaccine. The risk of clinical relapse of the disease is not increased with either vaccine

Disclosure of Interest: None declared

P0977 NUTRITIONAL ASSESSMENT IN ULCERATIVE COLITIS PATIENTS UNDER REMISSION: IS THERE A SINGLE RELIABLE TEST?

L. R. De Bona¹², C. F. D. M. Francesconi¹², A. S. Silva¹², M. H. I. Lopes¹², L. S. Harlacher¹, C. Flores¹²

¹Serviço de Gastroenterologia, Hospital de Clínicas de Porto Alegre, ²Programa de Pós Graduação: Ciências em Gastroenterologia e Hepatologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

Contact E-mail Address: lauradbona@yahoo.com.br

Introduction: The nutritional aspect of patients with UC has been poorly studied. The best nutritional assessment method has not been established. In the last years it has been seen a trend towards overweight and obesity among those patients, although some individuals, especially those with severe disease could be suffering from malnutrition

Aims & Methods: The aim of this study was to evaluate the nutritional status of patients with UC in clinical remission using different methods. Protocol approved by local IRB (number 130392). Methods: 80 individuals from a single center of southern Brazil from January 2014 to February 2015 were evaluated. Demographic data and assessment of high, weigh, body mass index (BMI), triceps skin fold (TSF) mid-arm circumference (MAC), mid-arm muscle circumference (MAMC), Subjective Nutritional Global Assessment (SGA), bioelectrical impedance (BIA), serum albumin and transferrin were performed. Statistical analysis was performed using chi-square, Wilcoxon-Mann-Whitney, Cochran and Kappa tests, assuming a 95% CI and statistic p < 0.05.

Results: Eighty individuals were included: 62% woman; mean age 45 ± 11.7 years and 96% Caucasian. Less then 5% were taking steroids. Malnutrition prevalence through different methods is shown on table 1. There was no association between malnutrition and disease duration and neither with extent of disease. None of the variables had any correlation when Kappa evaluation was applied. Laboratorial tests performed showed that only 1 subject had low albumin value and 28 (35%) showed low transferrin value. Considering BIA results 26.3% were considered body fat percentage above normal. Thirty seven percent were overweight and 16% obese by BMI.

Table 1.

Malnutrition Prevalence (anthropometry)

Method	N: 80
BMI < 18,5 e 22 (elderly) (%) a	2 (2.5%)
TSF < 50 percentile (%) b	58 (72.5%)
MAC < 50 percentile (%) b	44 (55%)
MAMC < 50 percentile (%) b	22 (27.5%)
SGA – mildly or significantly malnourished d	3 (3.8%)

Reference Range: ^a World Health Organization 1998; Lipchitz, 1994. ^b Frisancho 1981; 1990. ^cSchüssel et al, 2008. ^d Detsky et al.1987

Conclusion: Applying only one method is neither advisable nor reliable when assessing nutritional status. Our results show that a single patient could be considered malnourished by one and overweight by another. This study found a high percentage of overweight and obese UC patients in remission. However there are different frequencies depending upon the evaluation method that is used, BIA, anthropometric or BMI.

Disclosure of Interest: None declared

P0978 BEYOND MUCOSAL HEALING: TRANSMURAL AND EXTRAMURAL HEALING AFTER ONE-YEAR ANTI-TNFA THERAPY IN CROHN'S DISEASE

M. Serio¹, K. Efthymakis¹, A. Milano¹, A. Pierro², F. Laterza¹, G. Maselli², A. Bonitatibus¹, G. Sallustio², M. Neri¹

¹Medicine and Aging Sciences and CESI, Universita` “G. D’Annunzio", Chieti, <sup>2</sup>Radiology Department, Fondazione di Ricerca e Cura ‘‘Giovanni Paolo II’’, Universita` Cattolica del Sacro Cuore, Campobasso, Italy

Contact E-mail Address: mariaelenaserio@yahoo.it

Introduction: Crohn's disease (CD) is characterized by transmural (full-thickness) inflammation, frequently with extramural complications beyond to the mesentery and adjacent organs. The capability of anti-TNFα therapies in achieving and maintaining both clinical remission and mucosal healing (MH) has repeatedly been described, while only one study was designed to assess prospectively their role in transmural healing¹.

Aims & Methods: Aim of this study was to analyze transmural healing (TH) in consecutive CD patients after a one-year treatment with anti-TNFα and to correlate TH with endoscopic and clinical activity (CDAI) as well as biological markers (CRP and fecal calprotectin).

13 patients with moderate to severe ileocolic CD were enrolled. All underwent ileocolonoscopy and MRI-enterography before and after one-year treatment with anti-TNFα; clinical remission was defined as CDAI < 150, response as a 70-point reduction from baseline. CRP and fecal calprotectin (FC) (positivity cut-off respectively > 0.50 mg/dl and >150 μg/gr) were also measured. Endoscopic activity was assessed by SES-CD, range 0-40, with mucosal healing defined as score <3 and response as a 50% decrease from baseline. MRI activity was measured by MRI-enterography global score (MEGS), range 0-296, a score which takes into account transmural and extramural features, with active disease defined as a score ≥1, and response as above.

Results: We enrolled 6M/7F, mean age 36 ± 12 ys, mean disease duration 7 ± 5 ys. According to the Montreal classification the phenotype was L1 in 31%, L2 in 7% and L3 in 62%; the behaviour was B1 in 8%, B2 in 69% and B3 in 23%. Resectional surgery related to CD was observed in 15%. Signs of mesenteric inflammation were only lymph node enlargement or comb-sign. 3 patients were treated with IFX, 10 with ADA (all naive to anti TNFα). Mean SES-CD, MEGS, CDAI, CRP and FC values significantly decreased at one year (table). 53% had clinical remission, 77% clinical response. Biological remission was achieved in 69% and 53% according to FC and CRP respectively. MH was achieved 38%, endoscopic response in 46%. Normalization of MRI finding was achieved in 15%, 31% had transmural improvement; before therapy 85% showed at least one extramural sign of inflammation, after one year at least one sign persisted in 54% (p=ns). MEGS score after one year didn’t change significantly between patients with endoscopic remission/improvement and those without (p=0.7). CRP positivity at one year was correlated with presence of extramural involvement only (p=0.02) and mean CRP level were higher (2.3 ± 2.4 vs 0.30 ± 0.50 mg/dl) in the presence of comb-sign (p=0.03).

	Baseline	After one year	p value
SES-CD	10 ± 4	6 ± 4	p=0.002
MEGS	29 ± 13	17 ± 12	p=0.001
Transmural	22 ± 11	12 ± 9	p=0.001
Extramural	85% (at least one sign)	54% (at least one sign)	p=ns
CDAI	227 ± 88	147 ± 103	p=0.03
PCR	3,7 ± 4,1	1,2 ± 1,8	p=0.03
FC	388 ± 277	177 ± 148	p=0.03

Conclusion: Biological therapy is effective in inducing clinical, biochemical and endoscopical remission of CD while transmural inflammation may persist longer than one year. Transmural, mainly extramural, healing probably needs longer therapy to be achieved, and his activity was unrelated to endoscopic improvement while closely relates to CRP positivity and levels.

Disclosure of Interest: None declared

P0979 EFFICACY OF TUMOUR NECROSIS FACTOR ANTAGONISTS IN STRICTURING CROHN’S DISEASE: A TERTIARY CENTER REAL-LIFE EXPERIENCE

M. Allocca¹, G. Fiorino¹, C. Bonifacio², A. Spinelli³, I. Bravatà¹, A. Repici⁴, A. Malesci⁵, L. Balzarini², S. Danese¹

¹IBD Center, Gastroenterology, ²Radiology, ³Surgery, ⁴Digestive Endoscopy, ⁵Gastroenterology, Humanitas Research Hospital, Rozzano, Italy

Contact E-mail Address: sdanese@hotmail.com

Introduction: Stenosis is the most common complication in Crohn’s disease (CD). However, there are only limited data on the resolution of strictures induced by tumour necrosis factor antagonists in patients with stricturing CD.

Aims & Methods: 43 CD patients followed-up in a tertiary IBD Center between July 2006 and March 2015 were enrolled. All of them had stricturing CD (Ileal=40, colonic=3), diagnosed by colonoscopy and/or MRI enterography. Twenty-five subjects (58%) were given adalimumab, 18 (42%) infliximab. The primary outcome was to assess the rate of surgery due to stricturing CD. Statistical analysis included descriptive analysis, logistic regression with univariate analysis for risk factors, and Kaplan-Meier survival curve and Cox proportional hazards-regression analysis for estimation of efficacy of anti-TNFs in avoiding surgical resection. All differences were considered statistically significant for p < 0.05.

Results: 43 CD patients were analysed (20 males, median age 36 years, range 20-72). Median duration of disease was 3.92 years (range 0.26-29.52). After a median follow-up period of 41 months (range 7-105), 18/43 patients (41.86%) underwent abdominal surgery; 7/43 (38.8%) through the first year, 6/43 (33.3%) through the second year, 1/43 (5.5%) through the third year, 3/43 (16.6%) through the fourth year, and 1/43 (5.5%) through the fifth year. Patients treated with infliximab were more likely to delay or avoid surgery in the follow-up period (median survival time 67.47 months for infliximab vs. 49.03 months for adalimumab, HR 2.97; CI 95% 1.37 -11.10; p=0.01). Based on univariate analysis, only penetrating behavior at baseline was more likely to be associated with the risk of surgery (OR 3.96; CI 95% 1.0.7 to 14.6; p=0.039). Twenty patients over 43 (46.51%) continued anti-TNF therapy, 5/43 (11.62%) stopped treatment (1 for secondary loss of response, 2 psoriasis, 1 for pregnancy and 1 for recurrent tonsillitis). Patients treated with infliximab were more likely to avoid surgery than adalimumab (OR 2.80; CI 95% 0.05-2.0; SE 0.50; p= 0.0393).

Conclusion: Although in a small cohort, anti-TNF are effective in avoiding surgery in the long-term. Penetrating phenotype at baseline is associated with the risk of surgery. Patients treated with infliximab remained free of surgery longer than patients treated with adalimumab.

Disclosure of Interest: None declared

P0980 AZATHIOPRINE VERSUS AZATHIOPRINE-ALLOPURINOL TREATMENT IN INFLAMMATORY BOWEL DISEASE: A PROSPECTIVE TRIAL EVALUATING CLINICAL REMISSION AND ADVERSE EVENTS

M. Kiszka-Kanowitz¹, K. Theede¹, A. M. Nielsen¹

¹Hvidovre Hospital, Hvidovre, Denmark

Contact E-mail Address: marianne.kiszka-kanowitz@regionh.dk

Introduction: Low dose of Azathioprine (AZA) in combination with Allopurinol (ALLO) can be used in patients with inflammatory bowel disease (IBD) failing AZA therapy due to intolerance or to lack of efficacy. Combination of AZA-ALLO leads to increased levels of the active metabolite 6-Thioguanine-nucleotide (6-TGN) and simultaneously decreases the level of methylmercaptopurine (MeMP). Retrospective studies have shown that this combination therapy increases remission rates and eliminates some of the adverse events. Gaining experience with the combination therapy raises the question whether it is preferable to start patients on primary combination therapy instead of ordinary AZA therapy, thereby theoretically reducing intolerance and increase remission rates.

Aims & Methods: A prospective, single center, open label, randomized trial comparing efficacy and safety in AZA naïve IBD patients with normal thiopurine methyltransferase (TPMT) randomized to receive either standard weight-based dosing of AZA or combination therapy with AZA-ALLO.

Primary outcome was steroid and anti-TNFα free clinical remission (partial Mayo score ≤ 2 in UC or a Harvey-Bradshaw Index <5 in CD) at week 24 without adverse events.

Results: 23 IBD-patients were randomized to each treatment group. 16 patients (69.6%) in the AZA-ALLO-group compared to eight patients (34.7%) from the AZA-group achieved steroid and anti-TNFα free clinical remission at week 24 without experiencing adverse events. The difference in clinical remission between the two groups was statistic significant with RR=2.10 [CI:1.07-4.11].

Intolerance to treatment was observed in seven (30.4%) patients in the AZA-ALLO group compared to 11 (47.8%) patients in the AZA-group. Four patients in the AZA-group, otherwise tolerant to the treatment, failed to reach steroid and anti-TNFα clinical remission at week 24.

Only a single severe adverse event (severe anemia) was seen in a patient from the AZA-group. Three patients in the AZA-group and a single patient in the AZA-ALLO group had an infection. All 4 patients completed the study.

Seven patients that were withdrawn from the study from the AZA group due to intolerance or lack of efficacy accepted a trial of combination therapy with AZA-ALLO or 6-mercaptopurine (6-MP)-ALLO. Five of these patients tolerated the treatment with good clinical response. Five patients that were intolerant to AZA-ALLO treatment accepted a trial of 6-MP-ALLO, but only 2 patients tolerated this and had benefit of the treatment

Conclusion: Efficacy and tolerance rates are higher in patients treated with AZA-ALLO compared to standard therapy with AZA. These results could imply that combination therapy with AZA-ALLO can be used in AZA naïve patients with normal TPMT, thereby achieving higher remission rates and reducing the risk of intolerance to the therapy.

Disclosure of Interest: None declared

P0981 INCREASED WEIGHT GAIN IN ANTI-TNF ALPHA ANTIBODY TREATED PATIENTS WITH INFLAMMATORY BOWEL DISEASE MAY BE ATTRIBUTED TO LEPTIN AND TNF ALPHA

M. Protic¹, T. Schaffer², T. Knezevic¹, F. Seibold³

¹Department of Gastroenterology, University Hospital Zvezdara, Belgrade, Serbia, ²2. Departement Klinische Forschung, University of Bern, ³Department of Gastroenterology, Lindenhof Spital, Bern, Switzerland

Introduction: It is well known that TNF α, a critical mediator of inflammation in inflammatory bowel disease (IBD) is related to inflammation- related cachexia and anorexia. Animal studies have shown that body weight is regulated by adipocyte derived leptin. On the other hand, remarkable weight increase was observed among patients with IBD during treatment with anti- TNFα treatment. The association between weight increase, leptin and TNF α levels is unknown.

Aims & Methods: We retrospectively analyzed 132 patients with IBD, 102 on anti-TNF α therapies [Infliximab (IFX), Adalimumab (ADA)] and 30 patients on immunomodulators (IMD) (azathioprine, 6 MP) in a single tertiary IBD center. Levels of leptin, apelin and TNFα were measured in the serum of IBD patients, after at least 6 month of treatment with TNFα blockers or thiopurines by ELISA.

Results: A total of 106/132 (80%) IBD patients in our cohort had Crohn’s disease (CD), while 26/132 (20%) were diagnosed as Ulcerative Colitis (UC). No significant difference was found between initial body weights of the group on anti TNF-α therapy (65.96 ±18.93 kg) and IMD group (68.09 ± 17.03 kg) (p=0.911). 70% (72/102) of patients increased their body weight during the anti-TNF-α treatment (range 6–48 months) for median of 3.30 kg (range 0.0-40.0). Significantly higher levels of leptin (median 5.5 ng/ml, IQR 9) were found in the patient group on TNFα blockers compared to that on IMD therapies (median 2.5 ng/ml, IQR 6) (p= 0.049). Considerably lower levels of TNFα (median 6 ng/ml, IQR 14) were observed among patients on anti-TNFα therapies compared to IMD group (median 14.5 ng/ml, IQR 7) (p=0.02). No difference of apelin levels between two groups was detected (p= 0.791). No significant correlation between leptin serum levels and the increase of body weight was detected (Spearman coefficient r = 0.041, p= 0.684) as well as between the levels of TNFα and the body weight escalation (Spearman coefficient r = 0.036, p= 0.741).

Conclusion: The increase of weight gain in anti-TNF treated IBD patients may be attributed to elevated levels of leptin caused by the anti-TNF α treatment. A further mechanism is the reduction of TNFα itself.

Disclosure of Interest: None declared

P0982 ANTI-TNFA TREATMENT EFFICACY IN PREVENTION OF POSTOPERATIVE RECURRENCE IN CROHN’S DISEASE DEPENDS ON PREVIOUS EXPOSURE TO ANTI-TNFA AGENTS

M. Collins¹², H. Sarter³, C. Gower-Rousseau³, D. Koriche⁴, M. Nachury¹, L. Libier¹, A. Cortot¹, P. Zerbib⁴, J.-F. Colombel¹⁵, L. Peyrin-Biroulet⁶, P. Desreumaux¹, G. Pineton De Chambrun¹⁷

¹Gastroenterology Unit, University HOspital Lille, Lille, ²Gastroenterology Unit, Hôpital Bicêtre, Le Kremlin Bicêtre, ³Epidemiology, ⁴General Surgery department, University Hospital Lille, Lille, France, ⁵Gastroenterology Unit, Mount Sinaï Hospital, New York, United States, ⁶Gastroenterology Unit, University Hospital Nancy, Nancy, ⁷Gastroenterology Unit, University Hospital Montpellier, Montpellier, France

Contact E-mail Address: guillaume.pinetondechambrun@chru-lille.fr

Introduction: At least 50% of Crohn’s disease (CD) patients will need surgical resection during their follow-up. Infliximab and adalimumab are effective to prevent postoperative recurrence in CD patient naïve from anti-TNFα antibodies (anti-TNFα). The effect of previous exposure to one or more anti-TNFα before surgery on prevention of post-operative recurrence by these agents is still unknown.

Aims & Methods: The aim of our study was to investigate the efficacy of anti-TNFα to prevent CD post-operative recurrence according to previous exposure to these drugs.

We performed a retrospective analysis of CD patients, followed in a tertiary referral centre, who underwent surgical bowel resection and prophylactic treatment with anti-TNFα between January 2005 and June 2012. Infliximab, adalimumab and certolizumab pegol were considered as prophylactic treatments if started within three months after surgery. Endoscopic recurrence defined as a Rutgeerts score ≥ i2 and clinical recurrence defined as physician judgment. We assessed those endpoints one year after surgery and also during the follow-up.

Results: Fifty-seven consecutive CD patients with bowel resection, anastomosis and prophylactic treatment with anti-TNFα were included in the study. Twenty two patients (39%) had prior intestinal resection for CD and a majority (45, 79%) were treated with at least one anti-TNFα before surgery. Twenty-four (42%) received two or more anti-TNF before surgery and 12 (21%) patients were naïve from anti-TNFα. Thirty-nine (67%) patients had a surveillance colonoscopy one year after surgery. At one year, the global endoscopic and clinical postoperative recurrence rates were 42% (17/39) and 19% (11/57), respectively. According to previous exposure to anti-TNFα, patients with two or more anti-TNF before surgery had a higher one-year endoscopic recurrence rate compared with patients that received one or zero anti-TNFα before surgery (62%, n=13/21 vs. 31%, n=4/13 vs. 20%, n=1/5). Also, patients with two or more anti-TNFα before surgery had a higher rate of clinical recurrence compared with patients receiving less than two anti-TNFα before surgery (37%, n=9/24 vs. 12%, n=4/33, p=0.05). In multivariate analysis, smoking (HR=3.2; IC 95%: 1.2-7.8) and previous exposure to two or more anti-TNFα (HR=4.3; IC 95%: 1.3-14.0) were significantly associated to the risk of clinical postoperative recurrence in CD patients.

Conclusion: Previous exposure to two or more anti-TNFα agents was associated to a higher risk of postoperative recurrence in CD patients receiving prophylactic treatment with anti-TNFα.

This study suggested that previous exposure to anti-TNFα should be taken into account when managing prevention of post-operative recurrence in CD patients.

Disclosure of Interest: M. Collins Conflict with: Abbvie, H. Sarter: None declared, C. Gower-Rousseau Lecture fee(s): Janssen, Abbvie, MSD, D. Koriche: None declared, M. Nachury: None declared, L. Libier: None declared, A. Cortot: None declared, P. Zerbib: None declared, J.-F. Colombel: None declared, L. Peyrin-Biroulet: None declared, P. Desreumaux: None declared, G. Pineton De Chambrun: None declared

P0983 THE ROLE OF DIFFUSE NEUROENDOCRINE SYSTEM OF STOMACH AND INTESTINES IN THE OCCURRENCE OF IRRITABLE BOWEL SYNDROME WITH DIARRHEA IN CONJUNCTION WITH FUNCTIONAL DYSPEPSIA: THERAPY OPTIMIZATION

M. A. Osadchuk¹, V. O. Burdina¹, M. M. Osadchuk¹, K. S. Solodenkova¹

¹I. M. Sechenov First Moscow State Medical University, Moscow, Russian Federation

Contact E-mail Address: mikhail-osadchuk@mail.ru

Introduction: Endocrine cells (EC) of the gastric and intestinal mucosa secrete somatostatin (SS), vasoactive intestinal peptide (VIP) and motilin (MLN). The purpose of this study was to define the role of EC in the occurrence of irritable bowel syndrome with diarrhea (IBSd) in combination with functional dyspepsia (FD) and to optimize management of his comorbidity.

Aims & Methods: The study involved 45 patients with IBSd combined with FD. Inclusion criteria were age between 18 and 55 years; compatible with the Rome criteria III (2006) diagnosis of IBS and FD. The biopsy was taken during gastroscopy and colonoscopy from the antral mucosa and middle thirds of the sigmoid colon. Immunohistochemical examination was based on the use of murine monoclonal antibodies to SS, VIP and MLN (1: 100, Novocastra). All patients were randomized in a 1:1 ratio, depending on the nature of ongoing therapy. 22 patients (group 1) received therapy comprising proton pump inhibitors (PPI) in a dose of 40 mg per day, mebeverine (400 mg daily) and loperamide (until stool normalization). 23 patients (group 2) received dioctahedral smectite (1-3 sachets per day until stool normalization) instead of loperamide. Dynamic immunomorphological study was carried out at the manifestation of IBS and in remission after one month. The comparison group consisted of 20 healthy subjects.

Results: We defined increased number of EC, producing MLN and VIP, end reduced number of EC, synthesizing SS in mucous membrane of the antrum and colon in patients with IBSd in period of exacerbation, unlike the comparison group of persons. In the period of remission normalization of EC producing M, SS and VIP in the majority of patients was observed. In some patients the number of EC did not normalize, accompanied by the presence of residual symptoms. In group 1 stool normalization and epigastric pain disappearance were achieved in 20 patients at Day 4. In group 2 disappearance of the main clinical symptoms of FD and IBS was observed in 22 patients after 3 days of initiating therapy.

Conclusion: The obtained results suggest an important role of the diffuse neuroendocrine system in the occurrence of IBS with FD. Revealed changes in quantitative characteristic of EC in different parts of the digestive tract can explain the frequent combination of IBS with FD. Inclusion of dioctahedral smectite in drug therapy leads to an earlier clinical disappearance of disease but does not affect the quantitative characteristic of EC producing MLN, SS and VIP.

Disclosure of Interest: None declared

P0984 PREDICTORS OF DISEASE RELAPSE OF PATIENTS WITH CROHN'S DISEASE IN DEEP REMISSION: WHO AND WHEN CAN WITHDRAW THIOPURINE MAINTENANCE THERAPY?

Y. Qiu¹, R. Mao¹, B.-L. Chen¹, H. Yao¹, Z.-R. Zeng¹, M. Chen¹

¹Department of Gastroenterology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

Contact E-mail Address: qyun2012@gmail.com

Introduction: Few data are available on the disease course of cessation of thiopurine (TP) therapy for Crohn's disease (CD) with deep remission (DR) in routine clinical practice.

Aims & Methods: We aimed to evaluate clinical outcomes and factors associated with relapse in CD patients with DR. 109 CD patients in clinical, endoscopic remission following formal disease assessment and elective TP withdrawal were included. Prognostic factors of relapse were looked for through a proportional hazards model.

Results: After a median follow-up period of 46 months (interquartile range, 27.5-67.6 months), 50 (45.87%) patients had ER and 41 (37.61%) patients had flare, 18 (16.51%) patients undergone operation, and 25 (22.94%) patients hospitalized. The cumulative probabilities of maintaining clinical (P=0.48) or endoscopic remission (P=0.67), and free of bowel surgery (P=0.62) or hospitalization (P=0.72) at 5 years did not differ between patients maintaining TP or withdraw TP.

A scoring system based on age, CRP, disease duration and incidence of bowel complications was developed which can predict a mild prognosis after the achievement of DR, giving patients the chance of therapy de-escalation. In selective CD patients in DR without defined risk factors, up to 70% remained in clinical remission during the 60-month follow-up after the cessation of TP therapy. Importantly, 78% of these patients sustained endoscopic remission, 93.3% also free of bowel surgery.

Conclusion: No significant difference regarding the long-term outcomes of patients with DR maintaining TP or withdraw TP. Furthermore, a group of low-risked patients among whom therapy de-escalation maybe reasonably considered has been identified.

Disclosure of Interest: None declared

P0985 IMPACT OF LONG-TERM TREATMENT WITH AZATHIOPRINE ON DISEASE PROGRESSION IN PATIENTS WITH EARLY CROHN’S DISEASE

Y. Qiu¹, R. Mao², B.-L. Chen¹, Y. He¹, Z.-R. Zeng¹, M.-H. Chen¹

¹Department of Gastroenterology, ²First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

Contact E-mail Address: qyun2012@gmail.com

Introduction: The impact of azathioprine (AZA) on the damage-based long-term outcome of early Crohn’s disease (CD) still controversial. We aimed to evaluate the efficacy of AZA in patients with early CD.

Aims & Methods: To identify predictive factors associated with the long-term outcome of disease.

This longitudinal cohort study examined patients from a university-based IBD referral centre (2000 to 2013 year). Cox regression analysis was performed to identify potential predictive factors of CD progression.

Results: 190 Patients with early CD were followed- up prospectively for a total of 893 patient-years on AZA. After a median follow-up of 57 months (interquartile range, 31.3-76.2 months), 29 patients underwent abdominal surgery, 48 patients hospitalized, and 68 patients experienced clinical flare. The cumulative rate of free of CD- related bowel surgery, hospitalization and flare at 5-year on AZA treatment was 0.65, 0.59 and 0.39, respectively. The median CD-related bowel surgery-free survival, CD-related hospitalization-free survival and flare-free survival were 67.9 months (95% confidence interval (CI), 60.0-75.7), 67.9 months (95%CI 55.8-88.0), and 49.3 months (95%CI 34.9-63.7), respectively. Four independently predictors of Crohn’s related operations were identified: prior bowel resection (hazard ratio (HR), 9.91; 95%CI 3.74-26.24), smoking (HR, 4.79; 95%CI 1.75-13.17), an AZA treatment duration < 40 months (HR, 8.3; 95%CI 2.19-31.47) and a baseline hemoglobin <110 g/L (HR, 5.46; 95%CI 2.21-13.48). Prolonged use (≥40 months) of AZA also independently predictive of free of CD- related hospitalization (HR 3.02) but not increase risk of adverse events (P=0.23).

Conclusion: Prolonged use (≥ 40 months) of AZA was associated with a more favourable course of early CD (lower risk of CD- related bowel surgery and hospitalization) without increasing the risk of adverse events.

Disclosure of Interest: None declared

P0986 PREDICTING CHANGE TREATMENT IN CROHN’S DISEASE: A MEASUREMENT OF RISK SCORE

N. Pallotta¹, G. Vincoli¹, P. Pezzotti², M. Giovannone³, A. Gigliozzi³, D. Badiali¹, P. Vernia¹, E. S. Corazziari¹

¹Medicina Interna e Specialità Mediche, Università “Sapienza” Roma Italy, ²Istituto Superiore di Sanità, Rome, ³UOC Gastroenterologia Ospedale S. Camillo De Lellis, Rieti, Italy

Contact E-mail Address: nadia.pallotta@uniroma1.it

Introduction: Several independent predictors for complicated, severe or aggressive Crohn’ disease (CD) have been so far identified with a wide variation across studies (1). However progression disease predictors are not still clearly identified and it is not known whether the degree of bowel damage is a risk factor for disease progression. Intestinal ultrasound after the ingestion of oral contrast (SICUS) accurately measures CD small bowel intestinal lesions and complications (2).

Aims & Methods: To assess among demographic, clinical, laboratory factors and SICUS findings, those that may predict the modality of CD progression to identify with a easily used risk score patients requiring a more intensive monitoring and preventive treatments. This prospective cohort study includes 160 CD patients (93 M, median age 31 yrs; B1 25%, B2 56%, B3 19%; L1 61%, L3 32%, L2 6%; PD 29%) seen at regular 6-12 month interval, irrespective of clinical recurrence. During a median follow-up of 7.9 yrs, mean lag-time between visits 7.2 months, a total of 1464 visits (on average 9 per patient, range: 2-23), each assessing clinical, laboratory, endoscopic, and SICUS findings, were performed. By Poisson models we evaluated the predictors at each visit of having, within the next visit the need to change treatment starting azathioprine or biologics. Visit to visit interval was considered as exposure time. Independent predictors were: gender, age at diagnosis, CD duration, location and behavior, perianal disease, CDAI, GI symptoms, inflammatory markers, BMI, smoking, family history, SICUS findings, systemic symptoms, steroids at first flare, use of steroids, azathioprine and biologics, previous surgeries. Continuous variables were categorized based on the quartile values. The predictors included in the final model were chosen by a backward selection including at each step only variables with an adjusted p-value < 0.15. Standard errors of the Poisson parameter models were adjusted for visits clustering within the same patient. Risk scores were realized taking for each predictor the integer part of each model coefficient (i.e., the logarithm of the estimated incidence rate ratio (IRR)) (2) and then summing all those present at each visit, being zero the lowest possible score. Finally goodness-of-fit test was performed.

Results: Four independent factors predict the need to start biologics within the next visit: at SICUS the presence of 1) CD complications or 2) small bowel CD lesion >20 cm in absence of CD complications, 3) presence of specific intestinal symptoms; 4) the presence of inflammatory markers. The calculated integer risk score ranged from 0 to 5 points. Three independent factors predicts the need to start azathioprine within the next visit: 1) female gender; 2) BMI value <21; 3) CDAI at visit >50. The calculated integer risk score ranged from 0 to 4 points.

Conclusion: In CD patients a readily available risk score allows to identify those patients in need of more intensive monitoring and therapy

Disclosure of Interest: None declared

P0987 COMPARATIVE SHORT-TERM EFFICACY OF CYCLOSPORIN, TACROLIMUS, INFLIXIMAB AND ADALIMUMAB AS RESCUE THERAPY IN HOSPITALIZED PATIENTS WITH SEVERE CORTICOSTEROID REFRACTORY ULCERATIVE COLITIS: A RETROSPECTIVE INVESTIGATION

N. Yoshimura¹, R. Tanaka¹, M. Sako¹, M. Takazoe¹

¹Department of Internal Medicine, Division of IBD, Tokyo Yamate Medical Centre, Tokyo, Japan

Contact E-mail Address: ynaokun@yahoo.co.jp

Introduction: The optimum therapeutic strategy for patients with severe steroid refractory ulcerative colitis (UC) is still a challenging clinical issue. Currently, cyclosporin A (CsA), tacrolimus (Tac), infliximab (IFX), and adalimumab (ADA) have been administered as rescue therapy for severe steroid refractory UC. However, there is inadequate evidence for clinical efficacy difference between these 4 medications.

Aims & Methods: We were interested to evaluate the short-term efficacy and safety of CsA, Tac, IFX, and ADA as rescue therapy to avoid colectomy in patients with severe UC after failure of corticosteroids. This was a single-centre retrospective investigation involving 213 consecutive corticosteroid (iv, up to 60mg/day) refractory inpatients with acute severe to fulminant UC. Lichtiger’s clinical activity index (CAI) ≤ 16 meant severe UC, while CAI ≥ 17 meant fulminant UC. Patients received one of the following medications, iv CsA (initially 3mg/kg/day, aiming for blood levels of 400-600ng/ml, n=92), oral Tac (initially 0.05mg/kg twice a day, aiming for blood trough levels of 10-15ng/ml, n=46), IFX (5mg/kg at weeks 0, 2, n=47), or ADA (160mg at week 0, 80mg at week 2; n=28). Patients who did not improve after the first rescue therapy could switch to one of the other 3 medications as the 2nd rescue therapy or undergo colectomy. The primary clinical efficacy was evaluated at week 4 after the first rescue therapy. Further, at week 6, the efficacy of the 2nd rescue therapy was assessed. Clinical remission was defined as CAI ≤ 4. Additionally, patients received regular evaluations for adverse effects.

Results: Within 4 weeks, 156 of the 213 patients (73.2%) achieved remission with the first rescue therapy including 132 of 160 (82.5%) with severe UC and 24 of 53 (45.3%) with fulminant UC (P < 0.05). In the CsA group, 69 of 92 patients (75.0%) achieved remission vs 33 of 46 (71.7%) with Tac, 34 of 47 (72.4%) with IFX, and 20 of 28 (71.4%) with ADA (difference not significant). Further, for remission rate vs UC severity, with CsA, 49 of 58 (84.5%) patients with severe UC and 20 of 34 with fulminant UC (58.8%) achieved remission vs 31 of 38 (81.6%), and 2 of 8 (25.0%) for Tac, 32 of 40 (80.0%), and 2 of 7 (28.6%) for IFX, 20 of 24 (83.3%), and 0 of 4 for ADA (P < 0.05 for CsA vs Tac, IFX or ADA with respect to fulminant UC). After 6 weeks, 29 of 57 patients (50.9%) who had failed to respond to the first rescue therapy could avoid colectomy by switching to the 2nd rescue therapy. No patients experienced serious adverse events and there was no mortality.

Conclusion: In the first rescue therapy, the efficacy and safety of CsA, Tac, IFX and ADA were not significant different. In patients with fulminant UC, the efficacy of CsA was better than the other 3 medications for avoiding colectomy. Therefore, a 2nd rescue therapy should further reduce colectomy rate.

Disclosure of Interest: None declared

P0988 SHORTENING INTERVAL INJECTION OF ADALIMUMAB IS MORE EFFICIENT THAN DOUBLING DOSE IN CROHN'S DISEASE PATIENTS WITH LOSS OF RESPONSE

N. Duveau¹, M. Nachury¹, M. Boualit¹, R. Gerard¹, J. Branche¹, V. Maunoury¹, P. Desreumaux¹, B. Pariente¹

¹CHRU Lille, Université Lille 2, Lille, France

Contact E-mail Address: nicolas.duveau@gmail.com

Introduction: Adalimumab (ADA) is effective for the management of Crohn’s disease (CD), but relevant proportion of patients treated will experience a loss of response after a primary response. Response to dose escalation to ADA is a major concern in clinical practice as only few therapeutics agents have shown their efficacy in CD. The aim of the present study was to evaluate early and sustained response to ADA dose escalation for CD patients with secondary loss of response and to identify predictors of clinical response.

Aims & Methods: We conducted a retrospective observational study, including all patients who underwent a dose escalation of ADA after a secondary loss of response from 2007 to 2015. Main outcome was clinical response to dose escalation at weeks 12 (defined by continuation of ADA with no new dose escalation, no introduction of corticosteroids or immunosuppressors, and no surgery). Kaplan–Meier analysis was used to describe duration of sustained response after dose escalation over time. Univariate and multivariate logistic regression analyses were performed to identify predictors of response to ADA dose escalation at weeks 12 and 52.

Results: One hundred and twenty four patients were included. Among them, 81/124 (65%) had non-penetrating non-structuring disease, 31/124 (25%) structuring disease, and 12/124 (9%) penetrating disease. Fifty (40%) patients underwent previous intestinal resection. Sixty-seven (54%) patients received previous infliximab treatment. Median time to dose escalation was 44 weeks (IQR 18-117). At ADA dose escalation, 26/124 (20%) patients received concomitant immunosuppressors and 20/124 (12%) received concomitant corticosteroids. ADA dose escalation was achieved by shortening interval to 40 mg every week (ew) in 100/124 (80%) patients, and by increasing dose to 80 mg every other week (eow) for in 24/124 (19%) patients. Clinical response at weeks 12 was observed for 99/124 (79%) patients. In multivariate analysis, factors predicting response to ADA dose escalation at week 12 were a stricturing behavior (OR 2.55, 95% CI : 1.00-6.45 ; p=0.048) and duration of ADA therapy more than 44 weeks before ADA loss of response (OR 9.83, 95% CI : 1.25-76.81 ; p=0.029). In patients with initial response to ADA dose escalation at week 12, cumulative probabilities of sustained response were 91%, 76% and 58% at 6, 12 and 24 month, respectively. In multivariate analysis, shortening interval injection of ADA to 40 mg ew was the sole predictive factor of sustained clinical response at week 52 (OR 4.91, 95% CI : 1.00-24.24 ; p=0.05). Among all the patients, ADA was stop after dose escalation in 2 patients because of side effect (one for myocarditis and one for paradoxical psoriasiform skin lesions).

Conclusion: ADA dose escalation can recapture clinical response at week 12 in most CD patients who experienced a secondary loss of response to ADA; the majority of patients with initial response maintained clinical response over time. Importantly, shortening interval injection to 40 mg ew (compared to increasing dose to 80 eow) was the sole predictive factor for a sustained response to ADA dose escalation.

Disclosure of Interest: None declared

P0989 ENDOSCOPIC DILATATION OF CROHN’S ANASTOMOTIC STRICTURES IS EFFECTIVE IN THE LONG-TERM AND ESCALATION OF MEDICAL THERAPY IMPROVES OUTCOMES

N. S. Ding¹, Y. W. Man¹, B. Saunders², S. Thomas-Gibson², N. Arebi¹, A. Humphries², A. Hart¹

¹Inflammatory Bowel Disease, ²Wolfson Endoscopy Unit, St Mark's Hospital, London, United Kingdom

Contact E-mail Address: dingnik@gmail.com

Introduction: A clinically relevant stricture is usually defined as a luminal narrowing with pre-stenotic dilatation and obstructive symptoms. Surgical resection is an effective treatment for Crohn’s anastomotic strictures, however disease recurrence after 15 years is more than 50%, often with the need for a further resection[1]. The long-term outcome of endoscopic balloon dilatation is unclear as most cohorts have a follow-up time of less than 3 years.

Aims & Methods: All endoscopic balloon dilatations performed at a single centre for patients with anastomotic Crohn’s strictures between 2004-2009 were retrospectively reviewed with the aim of collecting long-term follow-up data. The stricture length, signs of disease activity and evidence of upstream dilatation were assessed from imaging. Clinical data on medical therapy and escalation to anti-TNF or thiopurines was obtained. Endoscopic data including disease activity, balloon size and therapeutic success, along with histological reports were recorded with images graded by an experienced endoscopist.

Results: A total of 54 patients were identified with a median age of 52 years (46-62). 21/54(39%) were male. The median follow-up period was 6 years(5-7) with a median disease duration of 28 years(19-32). Stricture length at cross-sectional imaging was described in all cases with a median of 20mm(10-30), features of active mucosal inflammation were described at the anastomosis in 38/54(70%) and upstream dilatation in 25/54(46%). At endoscopy, active disease was reported in 50/54(92%) of cases and a median balloon dilatation of 15mmHg was used to achieve therapeutic success in 48/54 (89%). The median number of dilatations was 2(IQR 1-9) with a time to repeat dilatation of 23months (7.2-56.9) with 31/44 (70%) of patients being managed endoscopically requiring repeat dilatations. There was one perforation which resulted in a resection of the anastomosis and temporary ileostomy.

Rutgeert’s grading of endoscopic images was possible in 50/54 cases with a median of i2 (range 1-4). 10 (18%) patients had anastomotic resection with a Rutgeert’s score of ≥i2 being positively associated with this outcome (p=0.048). Female gender (OR 1.604 95%CI 1.093-2.352 p=0.028), active disease at time of first endoscopy (OR 2.45 95% CI 1.145-5.234 p=0.021) and length of stricture >20mm (p=0.015) predicted need for repeat dilatation. Furthermore, escalation of medical therapy to either azathioprine or anti-TNF resulted in a delay in time to repeat dilatation in Cox-regression analysis.

Conclusion: At long-term follow-up only 18% of patients required surgical resection. Of the remaining patients 32% were well with no further endoscopic intervention required. 68% required intercurrent endoscopic dilatation. This is the longest follow-up period in the literature and demonstrates that endoscopic dilatation is effective and appropriate escalation of medical therapy appears to delay the need for further interventions.

Disclosure of Interest: None declared

P0990 PERSONALISING THERAPY: CLINICAL, HISTOLOGIC AND ENDOSCOPIC PREDICTORS OF ANTI-TNF OUTCOME IN CROHN’S DISEASE

N. S. Ding¹, T. Ganeshanathan¹, M. Yip¹, M. Samuel¹, C. Choi¹, S. Thomas-Gibson², B. Saunders², J. Warusavitarne³, M. Moorghen⁴, A. Hart¹

¹Inflammatory Bowel Disease, ²Wolfson Endoscopy Unit, ³Department of Surgery, ⁴Pathology, St Mark's Hospital, London, United Kingdom

Contact E-mail Address: dingnik@gmail.com

Introduction: Primary non-response (PNR) and secondary loss of response (LOR) are major issues affecting ongoing use of biological therapy in Crohn’s disease. Mucosal healing is currently the endpoint of many clinical trials and has been shown to improve outcomes. However, clinical or biochemical biomarkers of prediction for anti-TNF therapy are currently lacking.

Aims & Methods: We aim to determine factors using endoscopy and histology to predict PNR and secondary LOR with anti-TNF therapy in patients with Crohn’s disease.

Patients who were commenced on anti-TNF therapy (adalimumab or infliximab) from Jan 2007- June 2014 were identified along with clinical data, including demographics and phenotype. Patients with a colonoscopy and biopsies taken within 6 months of commencement of an anti-TNF and a further group with histology obtained within 12 months of their first dose were included. Each colonic segment of the colonoscopy was evaluated for activity of disease. Histology was assessed by a gastrointestinal pathologist who was blinded to the clinical data. PNR was defined by global assessment (clinical and biochemical) of lack of improvement within 6 months of commencement of anti-TNF therapy. Secondary LOR was defined as cessation of their anti-TNF in view of clinical deterioration as assessed by their gastroenterologist. Variables influencing PNR, secondary LOR and surgery were examined using the chi-square test, Wilcoxon rank-sum test and Cox-squared logistic regression

Results: 237 patients were identified; with 91 (38%) having ileal involvement (Table 1). There was no difference between PNR and secondary LOR in patients on combination therapy versus secondary LOR (p=0.12). PNR occurred in 36 (15%) patients and secondary LOR in 58 (24%) with 122 (51%) having ongoing anti-TNF therapy. Crypt architecture distortion was found in 64 (34%), lymphoid aggregates in 14% and granuloma(s) in 8%.

On univariate analysis, PNR was associated with smoking (p=0.048), >5 segments of disease at colonoscopy (p=0.012) and granuloma(s) (p=0.045) in a biopsy specimen. Ileal disease was associated with a greater likelihood of response (p=0.046). On univariate analysis, secondary LOR was associated with smoking (HR 2.53 p=0.018) and presence of lymphoid aggregates (HR 1.78 p=0.038). Multivariate analysis for PNR was significant for smoking and >5 diseased segments at colonoscopy. Multivariate analysis for secondary LOR factors was smoking. Cryptitis and crypt abcesses were not significant in either univariate or multivariate analyses.

Table 1.

Baseline characteristics of patients

Characteristics (n=237)	Median (IQR)
Age	30 (18-45)
Gender	45% male
Disease phenotype	Ileal involvement (38%)Stricturing disease (25%)
Duration of anti-TNF therapy	19 months (10-36).

Conclusion: Smoking is associated with PNR and secondary LOR. Extent of involvement (>5 segments of disease at colonoscopy) was associated with PNR. Histologic factors such as granuloma and lymphoid aggregates may contribute to prediction for PNR and secondary LOR respectively.

Disclosure of Interest: None declared

P0991 THE EFFECTIVENESS AND SAFENESS OF ALLOGENEIC MESENCHYMAL STROMAL CELLS IN PATIENTS WITH REFRACTORY CROHN'S DISEASE - 5 YEARS OF OBSERVATION

O. Knyazev¹, A. Kagramanova¹

¹Department of Inflammatory Bowel Disease, Moscow Clinical Research Center, Moscow, Russian Federation

Contact E-mail Address: oleg7@bk.ru

Introduction: Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract with recurrent nature of the flow. The frequency of exacerbations is approximately 20-25% at 1 year and 75% for 3 years. If the remission lasted less than 12 months, there is a 65% chance that the aggravation comes in the next 18 months. Aim. To evaluate the influence of culture of allogeneic mesenchymal stromal cells (MSCs) of bone marrow for the duration of remission in patients with refractory CD.

Aims & Methods: The 1-st group of patients with CD (n=30) received MSCs, the dose of prednisone was not more than 20 mg/day. The second group of patients (n=30) received standard anti-inflammatory drug therapy of 5-aminosalicylic acid (5-ASA) and glucocorticosteroids (GCS). Age of patients ranged from 19 to 49 years (Me-36 years). The disease was of moderate and high activity, length of damage - ileokolit, ileitis and colitis, the observation time ranged from 42 to 68 months. Clinical activity was assessed by the Crohn's disease activity index (CDAI). The culture of allogeneic MSCs injected drip at 2.5 million per 1 kg of body weight (0-1-26 weeks).

Results: CDAI in the 1st group was 242.6 ± 11.7 points, in the 2nd 240.9 ± 12.9 points (p=0.83), CRP levels in 1st group was 29.3 ± 6.4 mg/l, the 2nd - 27.8 ± 4.8 (p=0.47). After 1 year of follow-CDAI in 1st group was 70.0 ± 11.0 points, in the 2nd - 133.8 ± 22.2 points (p < 0.001), CRP levels in 1st group was 6.36 ± 1.5 mg/l, in the 2nd - 12.2 ± 2.9 (p < 0.001). After 2 years CDAI 1st group was 99.6 ± 19.3 points, in the 2nd - 147.1 ± 22.1 points (p < 0.001), CRP levels in 1-st group was 16.0 ± 6.0 mg/l, in the 2nd - 18.8 ± 4.4 (p=0.156). After 3 years, the CDAI in 1st group was 110.5 ± 21.9 points, in the 2nd - 180.6 ± 20.3 points (p < 0.001), CRP levels in 1st group was 10.9 ± 2.6 mg/l, in the 2nd - 16.9 ± 3.0 (p < 0.001). After 4 years - the CDAI in 1st group was 120.0 ± 22.3 points, in the 2nd - 208.7 ± 17.6 points (p < 0.001), CRP levels in 1st group was 11.3 ± 2.6 mg/l, in the 2nd - 15.5 ± 2.4 (p < 0.001). After 5 years - the CDAI in 1st group was 126.0 ± 23.8 points, in the 2nd - 248.7 ± 14.6 points (p < 0.001), CRP levels in 1st group was 12, 3 ± 2.8 mg/l, in the 2nd - 19.5 ± 3.1 (p <0.001). In the first group of patients in remission after 1, 2, 3, 4, and 5 years was kept at 70%, 56.6%, 50%, 46.7% and 33.3%, respectively. In the second group of patients at 1, 2, 3, 4, and 5-year remission was maintained at 36.6%, 26.6%, 13.3%, 6.67% and 6.67%, respectively. Complete healing of the intestinal mucosa in 60% of patients in the first group during the 1st year of observation, after 5 years - 26.7%. Over the entire period of observation never there were no malignant transformation, life-threatening infectious complications and death.

Conclusion: Transplantation of MSCs contributes to longer-term clinical and endoscopic remission in patients with refractory Crohn's disease compared with therapy with corticosteroids

Disclosure of Interest: None declared

P0992 CHANGES OF COLONIC MICROBIOTA AND EFFICACY OF ORAL PROBIOTIC THERAPY IN IBD

O. Plehutsa¹, R. Sydorchuk², L. Sydorchuk², I. Sydorchuk²

¹District Hospital, Briceni, Moldova, Republic of, ²Bukovinian State Medical University, Chernivtsi, Ukraine

Contact E-mail Address: supers_stars@uni.de

Introduction: The mechanisms explaining complex relationship between the commensal colonic microbiota and inflammatory bowel disease (IBD) have a common outcome, a violation of bacterial antigens exposure to effector T-cells and innate immune cells residing in the intestinal mucosa and/or alteration of the host immune response to bacteria. While the role of gut microbiota and respective immune changes has become more evident in recent years there is no sufficient database explaining the character of microbiota changes in IBD. Expanding this idea, probiotics have been the subject of intensive research, mainly focusing on bifidobacteria and lactobacteria. However, existing reports of probiotic use in IBD are contradictory.

Aims & Methods: The aim of this study was to find relation between changes of colonic microbiota and IBD, introduce rarely used probiotic, and understand whether oral probiotic therapy with P. Shermani has any therapeutic significance in IBD. Totally 104 individuals participate in the study. Colonic resistance studied in mucosal bioptates. Standard aerobic and anaerobic microbiology techniques with nosology identification and quantity composition of microbiota were used. Specially designed strain of P. Shermani (T73) with high antagonistic potential was orally given twice on a daily basis during 150-180 days in a form of suspension containing 10¹²-10¹⁴ bacteria. Patients without probiotic treatment formed control. Both groups' patients received mesalazine 1500-3000 mg daily as a basis therapy. Treatment efficacy evaluated according to WGO Global Guidelines and included CDAI, SF-36 and IBDQ scores.

Results: Major autochthonic species (14 in total) were present in all samples: among them Lactobacteria, Bifidobacteria, E. coli, several other anaerobic species were dominating. However, Lacto- and Bifidobacteria were found in significantly lower levels compared to healthy subjects (p=0.02-0.0031). The general tendency for colonic resistance in IBD was decrease of autochthonic anaerobes (Bifido-, Lactobacteria, Bacteroides spp, Clostridia spp, Bacillae spp.) and significant growth of allochtonic aerobes and facultative anaerobes (E.coli Hly+, Pseudomonas, Serratia, Hafniae, P. mirrabilis and other conditionally pathogenic Enterobacteriaceae). Enterococci were present in 60.0% of healthy and 7.14-20.69% of IBD patients. Staphylococci were present only in IBD group (17.24-31.58%). There were 16.67% and 22.22% recurrences requiring hospitalization during the study period. CDAI score at the end of study was 49.37 ± 3.14 points lower in study group (p < 0.05). SF-36 score difference between groups became 11.8 ± 0.84 %. Abdominal pain, stool, and drug use for symptomatic therapies improved in study group, too. However, probiotic treatment did not influence anemia and other extraabdominal symptoms. Endoscopic picture and biopsies presented no specific differences between groups after treatment.

Conclusion: Our data suggest that morbid changes of colonic mucosal microbiota, e.g. abnormal ratio of autochtonic and allochtonic species, may be considered as a strong characteristic feature of IBD. We hypothesized that results of existing studies of probiotic use in IBD are confusing due to improper selection of probiotic agent. P. Shermani T73 is comparatively rare and understudied probiotic, showing its usefulness for use in IBD.

Disclosure of Interest: None declared

P0993 6-THIOGUANINE AS AN ALTERNATIVE THERAPY IN INFLAMMATORY BOWEL DISEASE - EXPERIENCE IN A LONDON DISTRICT GENERAL HOSPITAL

O. S. Omer¹, S. Salehi¹, L. Pee¹, A. Gera¹, A. Loganayagam¹

¹Gastroenterology, Queen Elizabeth Hospital, Woolwich, London, United Kingdom

Contact E-mail Address: a.loganayagam@nhs.net

Introduction: Conventional thiopurines (Azathioprine/6-Mercaptopurine) remain the cornerstone of maintaining remission in steroid-dependent inflammatory bowel disease (IBD). Despite the well-documented efficacy of these drugs, more than 50% of patients discontinue treatment due to adverse events or therapy resistance. Over the past decade, there has been renewed interest in the use of 6-thioguanine (TG), an agent historically used in haematological malignancy. With a shorter metabolic pathway, TG possesses a favourable side effect profile and it’s use as an alternative thiopurine in IBD is growing. We report our experience in tolerability, safety and efficacy of TG use in a London district general hospital.

Aims & Methods: A retrospective review of electronic patient records including clinic letters, blood tests and endoscopic findings were carried out on patients commenced on TG between 2012 and 2015. Data was collected on patient demographics, indication and duration of therapy, response rates and reasons for treatment failure.

Results: A total of 28 patients received TG and median treatment duration was 14 months (range 1-40). Therapy was equally distributed amongst males and females (14:14), and mean age was 44 years (range 19-67). 14 (50%) patients had Ulcerative colitis (UC), 13 (46%) Crohn’s disease (CD) and 1 (4%) Indeterminate colitis. 24 patients (86%) received TG due to adverse reactions to conventional thiopurines vs. 3 patients (11%) who were non-responders. Treatment with TG resulted in clinical remission in 86% (19/22) patients at 6 months and 75% (12/16) at 12 months. In total, 6 patients (21%) discontinued TG. 4 patients failed treatment (2 continued alternative medical therapy and 2 had surgery) and 2 suffered adverse events (headaches and confusion). Tolerability and efficacy rates were similar in both UC and CD groups. All patients underwent blood monitoring and no abnormalities in liver function tests were detected. Of those who underwent MRI liver there was no evidence of nodular regenerative hyperplasia.

Conclusion: TG was well tolerated with comparable remission rates to conventional thiopurine therapy. We advocate the use of TG therapy in selected cases where conventional thiopurine therapy has failed or resulted in adverse reactions. Larger prospective trials are required to further evaluate the efficacy and safety of TG, with a view to potentially incorporate it’s use into clinical guidelines.

Disclosure of Interest: None declared

P0994 IMPACT OF ANTIBIOTIC TREATMENT BEFORE FAECAL MICROBIOTA TRANSPLANTATION (FMT) IN CHRONIC ACTIVE ULCERATIVE COLITIS

P. K. Kump¹, P. Wurm², H.-P. Gröchenig³, L. Reiter⁴, K. M. Hoffmann⁵, W. Spindelboeck¹, G. Reicht⁶, H. Wenzl¹, W. Petritsch¹, G. Gorkiewicz², C. Hoegenauer¹

¹Clinical Department of Gastroenterology, ²Institute of Pathology, University Hospital Graz, Graz, ³Dep of Internal Medicine, Convent Hospital St Veith, St. Veith, ⁴Dep of Internal Medicine, Convent Hospital Graz, ⁵Dep. of Pediatrics, University Hospital Graz, ⁶Clinical Department of Gastroenterology, Convent Hospital Graz, Graz, Austria

Contact E-mail Address: patrizia.kump@medunigraz.at

Introduction: Faecal microbiota transplantation (FMT) is investigated as a new therapeutic tool in chronic active ulcerative colitis (UC). The efficacy however, varies among distinct study protocols for FMT administration. The aim of this study was to investigate the impact of antibiotic treatment before FMT for therapy refractory chronic active UC.

Aims & Methods: 27 patients with chronic active UC were treated with an antibiotic triple therapy for 10 days. Afterwards 17/27 patients received FMT via colonoscopy into the right colon, which was repeated in 14 days intervals by sigmoidoscopy for a total of 5 applications (FMT group). 10/27 patients received antibiotic triple therapy without subsequent FMT and any other therapy (AB group). Clinical efficacy was assessed by total mayo score. Furthermore disease activity was also measured by faecal calprotectin and endoscopy. The follow up of the patients were 90 days and end of follow up to 30 weeks respectively.

Results: Antibiotic treatment led to an overall reduction of the Mayo score from 8.4 to 6.8 in all patients (9.0 to 7.3 in the FMT group; 7.5 to 5.9 in the AB group) within 10 days. In contrast to sole antibiotic therapy, FMT showed an additional benefit in the follow-up period of 30 weeks (total Mayo score FMT group 9.0 to 4.7 points vs 7.5 to 6.3 in the AB group). Adherence to therapy during follow up in the AB group was low (5/10; 50%) due to Clostridium difficile infection (3/10), acute UC flare (1/10) and antibiotic-associated diarrhea (n=1/10) vs. 100% in the FMT group. Overall, at day 90 clinical remission was assessed in 4/17 patients (total Mayo score < 2), partial responders in 6/17 patients (reduction of total Mayo score > 3 points) in the FMT group, versus partial response in 2/5 patients in the AB group.

Conclusion: Our data demonstrate a clinical benefit of antibiotic treatment before FMT in chronic active UC, whereas antibiotic therapy without consecutive FMT in chronic active UC is poorly tolerated.

Disclosure of Interest: None declared

P0995 USTEKINUMAB EFFICACY AND SAFETY IN CROHN’S DISEASE PATIENTS REFRACTORY TO CONVENTIONAL AND ANTI-TNF THERAPY: A MULTICENTER RETROSPECTIVE EXPERIENCE

P. Wils¹, Y. Bouhnik², P. Michetti³, B. Flourie⁴, H. Brixi⁵, J. Cosnes⁶, M. Allez⁷, B. Duclos⁸, J.-C. Grimaud⁹, A. Buisson¹⁰, A. Amiot¹¹, M. Fumery¹², X. Roblin¹³, L. Peyrin-Biroulet¹⁴, J. Filippi¹⁵, G. Bouguen¹⁶, V. Abitbol¹⁷, B. Coffin¹⁸, M. Simon¹⁹, D. Laharie²⁰, B. Pariente¹

¹CHRU Lille, Lille, ²Beaujon hospital, Clichy, France, ³Lausanne University Hospital, Lausanne, Switzerland, ⁴Lyon Sud hospital, Pierre-Bénite, ⁵Robert-Debré Hospital, Reims, ⁶Saint-Antoine Hospital, ⁷Saint-Louis Hospital, Paris, ⁸CHRU Hautepierre, Strasbourg, ⁹North Hospital, Marseille, ¹⁰University Hospital Estaing of Clermont-Ferrand, Clermont-Ferrand, ¹¹Henri Mondor Hospital, Créteil, ¹²CHU Amiens Nord, Amiens, ¹³University Hospital of Saint Etienne, Saint Etienne, ¹⁴Nancy University Hospital, Vandoeuvre-les-Nancy, ¹⁵University Hospital of Nice, Nice, ¹⁶University Hospital of Rennes, Rennes, ¹⁷Cochin Hospital, Paris, ¹⁸Louis Mourier Hospital, Colombes, ¹⁹Institut mutualiste montsouris, Paris, ²⁰Haut–Leveque Hospital, Pessac, France

Contact E-mail Address: pauline.wils@hotmail.fr

Introduction: Ustekinumab, a human monoclonal antibody against the p40 subunit of interleukin (IL)-12 and IL-23, has been shown to be effective in Crohn's disease (CD) patients refractory to anti-tumor necrosis factor (TNF) in a phase-2 trial.

Aims & Methods: The aim of the present study was to assess benefit and safety of subcutaneous (SC) ustekinumab in a multicenter cohort of anti-TNF refractory CD patients. A retrospective observational study was conducted in tertiary centers from the GETAID, including all consecutive active CD patients refractory to anti-TNF treatment, who received at least one SC injection of ustekinumab and had a follow-up of at least 3 months. The primary outcome was ustekinumab clinical benefit at 3 months, defined by a significant improvement as judged by the physician leading to continue the treatment with complete steroids weaning if given at inclusion. Ustekinumab safety and clinical benefit at 6 and 12 months were also recorded.

Results: One hundred twenty-two patients (87 females, median age: 38.8 years, IQR: 27.5-43.9) received at least one SC ustekinumab injection in 20 centers from France and Switzerland. At baseline, median disease duration was 12.9 years (IQR: 6.9-17.1); 119 (97.5%) patients experienced previous failure or intolerance to thiopurines or methotrexate and 122 (100%) patients have failed to at least one anti-TNF agent (infliximab or adalimumab, with 112 (91.8%) subjects who received both anti-TNFs) and 75 (61.5%) patients underwent prior intestinal resection. Ustekinumab was given for luminal CD to 110 (90.2%) patients and for perianal disease to 12 (9.8%). At inclusion, 18 (14.7%) patients received immunosuppressant (IS) and 19 (15.6%) steroids. Clinical benefit of ustekinumab at 3 months was observed in 79/122 (64.7%) patients in the whole population and in 8/12 (67%) patients treated for perianal disease. Concomitant IS at inclusion was the sole predictive factor of clinical benefit to ustekinumab at 3 months with an odds ratio of 5.43 (95% CI: 1.14- 25.77; p = 0.03). With a median follow-up duration of 9.8 months (IQR: 4.9-14.5 months), cumulative probability of maintained clinical benefit (without surgery, steroids or IS introduction) at 6 and 12 months was 92.8% and 68.2%, respectively. Twenty patients (16.4%) developed an adverse event with only one severe adverse event.

Conclusion: Clinical benefit of a SC ustekinumab induction was observed in two out of three CD patients and was maintained in majority of patients for up to 12 months. Pending results from ongoing trials, ustekinumab can be considered in CD patients refractory to anti-TNF agents.

Disclosure of Interest: P. Wils Lecture fee(s): Biogaran biosimilaires, Y. Bouhnik: None declared, P. Michetti: None declared, B. Flourie: None declared, H. Brixi: None declared, J. Cosnes: None declared, M. Allez: None declared, B. Duclos: None declared, J.-C. Grimaud: None declared, A. Buisson: None declared, A. Amiot: None declared, M. Fumery: None declared, X. Roblin: None declared, L. Peyrin-Biroulet : None declared, J. Filippi: None declared, G. Bouguen: None declared, V. Abitbol: None declared, B. Coffin: None declared, M. Simon: None declared, D. Laharie: None declared, B. Pariente: None declared

P0996 MAINTENANCE TREATMENT WITH GRANULOCYTE/MONOCYTE ADSORPTION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE AND AN INITIAL RESPONSE TO TREATMENT. A SWEDISH LONG-TERM PROSPECTIVE REGISTRY STUDY

A. Lindberg¹, S. Lindgren², M. Lördal³, S. Nilsson⁴, H. Svensson⁵, P. Karlen¹

¹Department of Clinical Science, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden, Stockholm, ²Department of Gastroenterology, University hospital Skane, Malmö, ³Department of medicine, Division of Gastroenterology and hepathology, Karolinska Institutet, Huddinge, Stockholm, ⁴Department of medicine, Kristianstad hospital, Kristianstad, ⁵Departments of Internal Medicine, Vrinnevi hospital, Norrköping, Sweden

Contact E-mail Address: per.karlen@ds.se

Introduction: Inflammatory bowel diseases (IBD) are chronic with different character and intermittent or more rarely continuous inflammatory activity. The activity ranges from mild to severe. The response to treatment varies and the choice of treatment is still partly arbitrary. Some patients represent a particular problem due to lack of response or intolerance to conventional treatment. There is a lack of data on results from maintenance treatment with Granulocyte/Monocyte Adsorption (GMA) in patients with an initial response to treatment.

Aims & Methods: 136 patients, 54 with ulcerative colitis (UC), 81 with Crohn´s disease (CD) and 1 with indeterminate colitis (IC) were included in a registry covering the majority of patients treated with GMA in Sweden. The disease activity was mainly mild or moderate. 49 IBD-patients initially achieving clinical response 3 month after a GMA course received maintenance treatment with GMA. The GMA maintenance treatments were scheduled with one of the following: one session monthly, every second month, every third month and every fourth month according to relapse rate and disease severity. Included patients were followed every third month for 12 months after induction GMA treatment. Monitoring includes symptoms (short health scale), activity indices (HBI, SCCAI) and fecal calprotectin.

Results: Overall, burden of symptoms, activity indices and fecal calprotectin levels remained at the same low level throughout the maintenance treatment period.

Conclusion: Maintenance treatment with GMA is effective in patients with an initial good response.

Disclosure of Interest: None declared

TUESDAY, OCTOBER 27, 2015   09:00-17:00

PAEDIATRIC: LOWER GI – HALL 7__________

P0997 METRONIDAZOL VERUS RIFAXIMIN IN THE TREATMENT OF CLOSTRIDIUM DIFFICILE INFECTION IN INFLAMMATORY BOWEL DISEASE CHILDREN: A RANDOMIZED STUDY

A. Gawronska¹, D. Lachowicz², I. Lazowska-Przeorek¹, K. Karolewska-Bochenek¹, M. Kotowska¹, P. Obuch-Woszczatyński², P. Albrecht¹, H. Pituch², A. Banaszkiewicz¹

¹Department of Pediatric Gastroenterology and Nutrition, ²Department of Medical Microbiology, Medical University of Warsaw, Warsaw, Poland

Contact E-mail Address: aleksandra.banaszkiewicz@gmail.com

Introduction: The aim of the study was to compare the effectiveness of metronidazole and rifaximin in the treatment of Clostridium difficile infection (CDI) in pediatric patients with inflammatory bowel disease (IBD).

Aims & Methods: We conducted a prospective, double-blinded, randomized trial with children age 12-18 years. Crohn’s disease (CD) and ulcerative colitis (UC) were diagnosed according to Porto criteria. CDI diagnosis was based on a positive stool VIDAS® Clostridium difficile toxin A/B ELFA (bioMerieux, France) test. Patients were randomly assigned to receive metronidazole or rifaximin for 14 days; doses of drugs were weight-adjusted. Stool samples were collected before and 4 weeks after the end of treatment.

Results: In the present study, 26 patients were enrolled (mean age 14.3 years), including 9 with CD and 17 with UC. 14 received metronidazole and 12 received rifaximin. There were no statistically significant differences between study groups in age, gender and disease type. 4 weeks after the end of treatment Clostridium difficile toxins were found in 5/14 (36%) patients in metronidazole group and in 4/12 (33.3%) patients in rifaximin group (n=NS).

Conclusion: Metronidazole and rifaximin was equally effective in the treatment of CDI in pediatric patients with IBD.

Disclosure of Interest: None declared

P0999 ITEM GENERATION AND REDUCTION OF THE “TUMMY” INDEX, A NEWLY DERIVED PATIENT REPORTED OUTCOME (PRO) FOR PEDIATRIC ULCERATIVE COLITIS

L. Marcovitch¹, A. Nissan¹, D. Mack², A. Otley³, S. Hussey⁴, M. Kappelman⁵, B. Mclean⁵, N. Croft⁶, F. Barakat⁶, A. Griffiths⁷, D. Turner¹

¹Shaare Zedek Medical Center, Jerusalem, Israel, ²CHEO, Ottawa, ³IWK, Halifax, Canada, ⁴University College Dublin, Dublin, Ireland, ⁵UNC Health Care, North Carolina, United States, ⁶Barts and the London School of medicine, London, United Kingdom, ⁷SickKids, Toronto, Canada

Contact E-mail Address: turnerd@szmc.org.il

Introduction: The Pediatric Ulcerative Colitis Activity Index (PUCAI) is a non-invasive clinician-based index, proven to reflect well mucosal inflammation in pediatric ulcerative colitis (UC). Under the qualification program of the FDA and EMA, we aimed here to develop a Patient Reported Outcome (PRO) measure of signs and symptoms for pediatric UC (i.e. the TUMMY index) to complement the PUCAI, when used with endoscopic assessment. The derived questionnaire will enable calculating both the TUMMY and the PUCAI scores independently.

Aims & Methods: We performed qualitative interviews- 35 with UC children (age 12.3 ± 3.2, range 4-18 years; 50% males; 83% with extensive colitis; 25% with moderate-severe disease) and 25 with their caregivers, in Israel, England, Ireland, Canada and the USA, to ensure cultural diversity. Interviews were centered at exploring signs and symptoms reflecting the colitis and which are important to children. Items were rank ordered according to the frequency of endorsement and importance, graded on a 1-5 scale by the interviewees.

Results: There was a general agreement between the total scoring of the children and their caregivers. The following items were identified in decreasing order of weights (importance X frequency): abdominal pain (4), rectal bleeding (3.5), stool frequency (2.8), stool consistency (2.8), general well-being (2.8), urgency (1.8), and nocturnal stools (1.7). Two other items were scored low and are perceived as having low accuracy (lack of appetite (1) and weight loss (0.6)). Children 13-18 years comprehended adult vocabulary, 8-12 years simple vocabulary and younger children had poor understanding and thus their disease may be more accurately scored by a caregiver-reported questionnaire.

Conclusion: In this first report of the TUMMY development, items were generated and ranked by input purely from patients. These items are now being explored for optimal vocabulary and response options. The TUMMY index will supplement the PUCAI in clinical trial outcome assessment.

Disclosure of Interest: L. Marcovitch: None declared, A. Nissan: None declared, D. Mack: None declared, A. Otley: None declared, S. Hussey: None declared, M. Kappelman: None declared, B. Mclean: None declared, N. Croft: None declared, F. Barakat: None declared, A. Griffiths: None declared, D. Turner Financial support for research: This study was funded by a grant from Janssen, Conflict with: Royalties from SickKdis

P1000  RELATIONSHIP OF THE PEDIATRIC CROHN’S DISEASE ACTIVITY INDEX (PCDAI) AND CROHN’S DISEASE ACTIVITY INDEX (CDAI) IN IMAGINE 1

D. Turner¹, J. Hyams², M. Dubinksy³, W. Faubion⁴, S. Eichner⁵, Y. Li⁵, A. Lazar⁶, B. Huang⁵, R. Thakkar⁵

¹Shaare Zedek Medical Centre, Jerusalem, Israel, ²Connecticut Children’s Medical Center, Hartford, ³Mount Sinai Hospital, New York, ⁴Mayo Clinic, Rochester, ⁵AbbVie Inc., North Chicago, United States, ⁶AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany

Introduction: The Pediatric Crohn’s Disease Activity Index (PCDAI) assesses disease activity in children and adolescents with Crohn’s disease (CD), and was developed to take in account more objective measures than the Crohn’s Disease Activity Index (CDAI). Although both indices have similar components, the PCDAI includes additional laboratory measures and disease features specific to children and adolescents with CD. In IMAgINE 1, a 52-week (wk), phase 3, multicenter, randomized open-label induction/double-blind maintenance trial of adalimumab (ADA) in 192 patients aged 6–17 yrs with CD, both PCDAI and CDAI were calculated for patients aged 13–17 yrs.¹

Aims & Methods: This post-hoc analysis evaluated concordance of remission status based on PCDAI and CDAI. Patients in IMAgINE 1 had CD with a baseline PCDAI score >30 and were intolerant or resistant to conventional therapy. Patients received open-label ADA induction at weeks 0/2 based on body weight (≥40 kg, 160/80mg; <40 kg, 80/40 mg). At wk 4, patients were randomized to higher (≥40 kg, 40 mg every other wk [eow]; <40 kg, 20 mg eow) [HD] or lower dose (≥40 kg, 20 mg eow; <40 kg, 10 mg eow) ADA maintenance therapy. The agreement of PCDAI remission (PCDAI score ≤10) and CDAI remission (CDAI score <150) at wks 26 and 52 was evaluated in both dosing groups combined. Non-responder imputation was used for missing data.

Results: Of 188 patients who entered the double-blind maintenance period of IMAgINE 1, 122 were aged 13–17 yrs. PCDAI remission rates at weeks 26 and 52 were 37% (45/122) and 31% (38/122), respectively; CDAI remission rates at weeks 26 and 52 were 51% (62/122) and 36% (44/122), respectively. At wk 26, 36% (44/122) patients achieved both PCDAI and CDAI remission, and 48% (59/122) had neither PCDAI nor CDAI remission (Table); thus, the agreement between measures was 84% (Kappa=0.6899; p < 0.001) At wk 52, 30% (37/122) patients achieved both PCDAI and CDAI remission, and 63% (77/122) had neither PCDAI nor CDAI remission (Table); thus, the agreement between measures was 93% (Kappa=0.8535; p < 0.001).

Abstract number: P1000 Table.

Concordance and discordance of PCDAI remission and CDAI remission in patients aged 13–17 yrs with CD treated with ADA in IMAgINE 1.

Week	PCDAI remission & CDAI remissionn (%)	No PCDAI remission & no CDAI remissionn (%)	Concordantn (%)	No PCDAI remission & CDAI remissionn (%)	PCDAI remission & no CDAI remissionn (%)	Discordantn (%)
26	44 (36.1)	59 (48.4)	103 (84.4)	18 (14.8)	1 (0.8)	19 (15.6)
52	37 (30.3)	77 (63.1)	114 (93.4)	7 (5.7)	1 (0.8)	8 (6.6)

Conclusion: Agreement among PCDAI and CDAI was moderate to substantial at weeks 26 and 52. However, CDAI may over estimate remission in pediatric CD given the higher overall rates of remission by this metric. The agreement of PCDAI and CDAI with other outcome measures requires further exploration.

Disclosure of Interest: D. Turner Financial support for research: MSD, Janssen, Shire, Pfizer, Hospital for Sick Children, Ferring, AbbVie and Abbott, Consultancy: MSD, Janssen, Shire, Pfizer, Hospital for Sick Children, Ferring, AbbVie and Abbott, Conflict with: MSD, Janssen, Shire, Pfizer, Hospital for Sick Children, Ferring, AbbVie and Abbott, J. Hyams Lecture fee(s): Janssen Orthobiotech, AbbVie, TNI Biotech, EnteraHealth, Pfizer, Soligenix, Takeda, Consultancy: Janssen Orthobiotech, AbbVie, TNI Biotech, EnteraHealth, Pfizer, Soligenix, Takeda, Conflict with: Janssen Orthobiotech, M. Dubinksy Financial support for research: Janssen, Consultancy: AbbVie, Janssen, Takeda, Pfizer, Prometheus labs, Santarus, UCB, W. Faubion Consultancy: Genentech, Implicit Biosciences, Connecticut Children’s Medical Center - Safety officer on subcontracted award through NIH for clinical trial, Directorship(s): AbbVie, Shire Development, Inc - Pediatric UC Advisory Board, Janssen Services LLC - DEVELOP Registry Scientific Advisory Committee, UCB Biosciences Advisory board, S. Eichner Shareholder: AbbVie, Y. Li Shareholder: AbbVie, A. Lazar Shareholder: AbbVie, Conflict with: AbbVie, B. Huang Shareholder: AbbVie, Conflict with: AbbVie, R. Thakkar Shareholder: AbbVie, Conflict with: AbbVie

P1001 INCIDENCE AND PHENOTYPE AT DIAGNOSIS IN VERY EARLY COMPARED TO LATER-ONSET PEDIATRIC INFLAMMATORY BOWEL DISEASE: A POPULATION-BASED STUDY (1988-2011)

E. Bequet¹, H. Sarter², M. Fumery³, L. Armengol-Debeir⁴, B. Pariente⁵, D. Ley¹, C. Spyckerelle⁶, L. Peyrin-Biroulet⁷, G. Savoye⁴, D. Turck¹, C. Gower-Rousseau²⁸, on behalf of Epimad Registry on behalf of Epimad Registry

¹Pediatric Unit, ²Epidemiology, University and Hospital Lille, Lille, ³Gastroenterology, Amiens University & Hospital, Amiens, ⁴Gastroenterology, Rouen University & Hospital, Rouen, ⁵Gastroenterology, University and Hospital Lille, ⁶Pediatric Unit, Hôpital St Vincent, Faculté Catholique, Lille, ⁷Gastroenterology, Nancy University & Hospital, Nancy, ⁸Liric - Umr 995 Inserm, Université Lille 2 / CHRU de Lille, Lille, France

Contact E-mail Address: corinne.gower@chru-lille.fr

Introduction: Age at diagnosis of inflammatory bowel disease (IBD) in children has taken an important role and very early onset IBD (VEO-IBD; diagnosis < 6 years) seem to be a form of IBD distinct from that of older children.

Aims & Methods: We aimed to compare the incidence and phenotype at diagnosis of VEO-IBD and IBD in older children (6-17 years) from a French population-based study over a 24-year period. We extracted the pediatric IBD cohort through the population-based Registry from 1988 to 2011.

Results: In total, 1412 children (8% of all IBD) have been recorded including 42 (3%) with VEO-IBD. The incidence of overall IBD in children increased from 3.0/10⁵ in 1988-1990 to 6.3 in 2009-2011 (+110 %; p < 10^-3). The incidence remained stable among VEO-IBD children (0.4/10⁵ from 1988-1990 to 2009-2011) while it increased from 1.6 to 3.5/10⁵ (+119%; p < 10^-3) among 6-9 years old, and from 6.1 to 13.1/10⁵ (+115%; p < 10^-3) among children ≥ 10 years old. The initial classification as ulcerative colitis (UC) or IBD unclassified (IBDU) was more common among the VEO-IBD group (40% vs 26%; p=0.05). Differences in phenotype according to age at diagnosis are summarized in the Table.

Variables at diagnosis	< 6 years at diagnosis	6-17 years at diagnosis	P-value
All IBD	N=42 (3%)	N=1370 (97%)
Crohn’s Disease (CD)	N=25 (60%)	N=1007 (74%)
UC	N=14 (33%)	N=329 (24%)
Diagnosis at Hospital	69%	42%	< 10-3
Male	52%	52%	0.92
Diarrhea	76%	66%	0.15
Rectal bleeding	81%	45%	< 10-4
Mucous stools	40%	21%	< 10-2
Abdominal pain	43%	74%	< 10-4
Weight loss	21%	49%	< 10-3
EIMs*	17%	17%	0.97
Growth failure (Z score weight/height < 2)	17%	10%	0.14
Diagnosis delay > 6 months	27%	30%	0.67
IBD family history	9%	15%	0.30
Complicated behavior in CD (B2 + B3**)	5%	17%	0.20
Anoperineal lesions in CD	8%	6%	0.65
Pure colonic location in CD (L2**)	36%	13%	< 10-2
Proctitis in UC (E1**)	9%	30%	0.12
Extensive colitis in UC (E4**)	55%	43%	0.31

* Extra intestinal manifestations

** According to Paris classification

Conclusion: According to the present retrospective population-based study, the incidence of VEO-IBD was low and remained stable from 1988 to 2011. Children diagnosed with VEO-IBD were more often diagnosed in hospital than those diagnosed after the age of 6. VEO-CD children presented more rectal symptoms, presumably in relation to a high prevalence of isolated colonic CD.

Disclosure of Interest: None declared

P1002 PREVENTION OF LOSS OF RESPONSE TO TNF-A BLOCKERS IN PAEDIATRIC AND ADULT IBD PATIENTS BY USING THE GRAZ ALGORITHM

E. Zöhrer¹², F. Kelz², W. Petritsch², C. Högenauer², H. Wenzl², W. Erwa², J. Jahnel²

¹Department of Paediatrics and Adolescent Medicine, ²Medical University Graz, Graz, Austria

Contact E-mail Address: e.zoehrer@medunigraz.at

Introduction: Treatment in inflammatory bowel diseases (IBD; Crohn’s disease [CD] and ulcerative colitis [UC]) has improved due to biologics. However, a problem is loss of response (LOR) maybe due to the formation of antibodies against these biologics. Our aim was to investigate antibody response against standard biologics infliximab (IFX) and adalimumab (ADA) in paediatric and adult patients with IBD and develop an algorithm to avoid a LOR.

Aims & Methods: We conducted a prospective, multi-center study assessing antibody levels in IBD patients with active disease by an enzyme-linked immunoassay (Immunodiagnostik AG, Bensheim, Germany) which is able to measure free and bound antibodies against IFX or ADA. We investigated a possible correlation between LOR during therapy and positive antibodies and furthermore linked clinics with antibody levels. LOR was defined as dose escalation, discontinuation of treatment or shortening of dosage interval.

Results: One-hundred-and-eighty-eight patients were included. 27/91 of CD patients (30%) and 12/45 (27%) of UC patients with IFX therapy showed positive antibody levels. In the ADA group in 3/46 (7%) with CD and 1/6 (17%) with UC antibodies were detected. 27% of antibody-positive CD patients and 100% of UC patients with IFX therapy had a LOR, whereas 67% of antibody-positive CD patients and 100% of UC patients had a LOR under ADA. Correlation with clinics showed that most of the patients with positive antibodies showed low IFX or ADA levels with 63% and 43%, respectively. Furthermore, an algorithm was developed including drug monitoring for dose optimization and antidrug monitoring to consider switch of medication.

Conclusion: Our study suggests that occurrence of antidrug antibodies is a frequent event associated with LOR. By using an algorithm antidrug and drug monitoring may support optimal treatment of paediatric and adult patients receiving biological therapies in IBD.

Disclosure of Interest: None declared

P1003 BURDEN OF DISEASE IN PAEDIATRIC PATIENTS WITH MODERATE VERSUS SEVERE CROHN’S DISEASE IN THE IMAGINE 1 TRIAL

F. Ruemmele¹, J. Hyams², J. Rosh³, M. Dubinsky⁴, J. Markowitz⁵, A. Griffiths⁶, D. Turner⁷, J. Escher⁸, S. Eichner⁹, A. Lazar¹⁰, A. M. Robinson⁹, B. Huang⁹, R. Thakkar⁹

¹Université Sorbonne Paris Cité, Hôpital Necker-Enfants Malades, Paris, France, ²Connecticut Children’s Med Ctr, Hartford, ³Goryeb Children’s Hosp/Atlantic Health, Morristown, ⁴Mount Sinai Hosp, NY, ⁵Cohen Children’s Med Ctr of NY, New Hyde Park, United States, ⁶The Hosp for Sick Children, Toronto, Canada, ⁷Shaare Zedek Med Ctr, Jerusalem, Israel, ⁸Erasmus MC-Sophia Children's Hosp, Rotterdam, Netherlands, ⁹AbbVie, N Chicago, United States, ¹⁰AbbVie Deutschland GmbH & Co KG, Ludwigshafen, Germany

Contact E-mail Address: samantha.eichner@abbvie.com

Introduction: Biologic therapy is generally reserved for children with moderate to severe Crohn’s disease (CD), however, distinguishing moderate from severe disease by the Paediatric CD Activity Index (PCDAI) can be difficult.¹

Aims & Methods: To compare disease burden in patients (pts) classified as moderate vs severe by PCDAI in IMAgINE 1,² a 52 week (wk) trial of adalimumab in which pts aged 6-17 years with CD and baseline (BL) PCDAI >30 were enrolled. All pts had failed concurrent or prior corticosteroids (CS) and/or immunomodulators (IMM) therapy. Infliximab (IFX)-exposed pts could enroll. BL characteristics, demographics, and the proportion of pts with a BL score of 10 (worst score) for at least one of the PCDAI components of abdominal pain (AP), stool frequency (SF), and general well-being (GW) were assessed in pts with moderate (PCDAI <40) and severe CD (PCDAI ≥40) as defined by the median PCDAI at BL.

Results: The intent-to-treat population included 188 of 192 pts enrolled. 43% (80) had moderate and 57% (108) had severe CD at BL. Demographics, CD activity, prior and concomitant CD-related IMM and CS use, prior IFX use, and IMPACT III scores at BL were similar for both groups (Table). Median CRP was numerically higher in pts with severe vs moderate CD (1.76 vs 0.65 mg/dL), but ranges largely overlapped. A similar proportion of pts with moderate and severe CD (83 vs 95%) had the most severe score of 10 at BL for at least one of the PCDAI components of AP, SF, or GW.

Abstract number: P1003 Table.

Demographics and baseline characteristics by disease severity (intent-to-treat population )

	Moderate CD (PCDAI < 40) (N=80)	Severe CD (PCDAI ≥ 40) (N=108)
Age, years, mean (SD)	14.0 (2.4)	13.4 (2.5)
Male, n (%)	41 (51.3)	64 (59.3)
CRP, mg/dL, median (range)	0.65 (0, 16.8)a	1.76 (0, 14.4)
Prior CD-related immunomodulator use, n (%)	73 (91.3)	96 (88.9)
Prior CD-related corticosteroid use, n (%)	59 (73.8)	86 (79.6)
Prior infliximab use, n (%)	32 (40.0)	51 (47.2)
Concomitant CD-related immunomodulator use, n (%)	51 (63.8)	66 (61.1)
Concomitant CD-related corticosteroid use, n (%)	26 (32.5)	45 (41.7)
Disease duration , year, mean (SD)	3.1 (2.3)	2.9 (2.2)
PCDAI, mean (SD)	34.8 (2.4)	45.7 (5.5)
CD location, n (%)
-Anal/Perianal	20 (25.0)	34 (31.5)
-Colon	67 (83.8)	87 (80.6)
-Ileum	64 (80.0)	81 (75.0)
Draining fistulas, n (%)	12 (15.0)	24 (22.2)
IMPACT III score, mean (SD)	118.2 (16.1)b	112.0 (18.0)c
aN=78, bN=77, cN=104

Conclusion: Clinical characteristics and treatments administered to pts with moderate or severe disease activity by PCDAI were similar. Overall, the disease burden in the moderate pts was similar to severe pts in IMAgINE 1.

Disclosure of Interest: F. Ruemmele Lecture fee(s): Schering-Plough, Nestlé, MeadJohnson, Ferring, MSD, Johnson & Johnson, Centocor, Conflict with: Board membership: SAC:DEVELOP (Johnson & Johnson); invited to: MSD France, Nestlé Nutrition Institute, Nestlé Health Science, Danone, MeadJohnson, Biocodex, J. Hyams Lecture fee(s): Janssen Orthobiotech, Consultancy: Janssen Orthobiotech, AbbVie, TNI Biotech, EnteraHealth, Pfizer, Soligenix, Takeda, Conflict with: Expert testimony and payment for development of educational presentations for Janssen Orthobiotech., J. Rosh Financial support for research: AstraZeneca, AbbVie, Janssen, UCB, Lecture fee(s): Abbott Nutrition, Prometheus, Consultancy: AbbVie, Janssen, Soligenex, Conflict with: Board membership: GI Health Foundation, M. Dubinsky Financial support for research: Janssen, Consultancy: AbbVie, Janssen, Takeda, Pfizer, Prometheus labs, Santarus, UCB, J. Markowitz Consultancy: AbbVie, Janssen OrthoBiotech, UCB, Soligenix, A. Griffiths Financial support for research: Johnson and Johnson, Abbvie, Lecture fee(s): AbbVIe, Consultancy: Abbvie, Nutricia, Janssen Canada, MSD; Ferring; Shire, Conflict with: Educational program support: Abbvie; Janssen Canada, D. Turner Financial support for research: MSD, Lecture fee(s): MSD, Consultancy: Janssen Biologics, Conflict with: Board membership: scientific advisory committee of DEVELOP study (Janssen Biologics), J. Escher Financial support for research: MSD, Lecture fee(s): MSD, Consultancy: Janssen Biologics, Conflict with: scientific advisory committee of DEVELOP study (Janssen Biologics), S. Eichner Conflict with: AbbVie employee, may own AbbVie stock and/or options, A. Lazar Conflict with: AbbVie employee, may own AbbVie stock and/or options, A. Robinson Conflict with: AbbVie employee, may own AbbVie stock and/or options, B. Huang Conflict with: AbbVie employee, may own AbbVie stock and/or options, R. Thakkar Conflict with: AbbVie employee, may own AbbVie stock and/or options

P1004 REDUCTION OF ANTI-INFLIXIMAB ANTIBODY FORMATION IN PAEDIATRIC CROHN’S PATIENTS ON CONCOMITANT IMMUNOMODULATORS

H. M. Kansen¹, P. F. van Rheenen², R. H. Houwen¹, W. Tjon, A. Ten³, G. M. Damen⁴, A. Kindermann⁵, J. C. Escher⁶, V. M. Wolters¹

¹Paediatric Gastroenterology, University Medical Centre-Wilhelmina Children’s Hospital, Utrecht, ²Paediatric Gastroenterology, University Medical Centre Groningen-Beatrix Children’s Hospital, Groningen, ³Paediatric Gastroenterology, Maxima Medical Centre, Veldhoven, ⁴Paediatric Gastroenterology, Radboud University Medical Centre-Amalia Children’s Hospital, Nijmegen, ⁵Paediatric Gastroenterology, AMC Medical Centre-Emma Children´s Hospital, Amsterdam, ⁶Paediatric Gastroenterology, Erasmus Medical Centre-Sophia Children’s Hospital, Rotterdam, Netherlands

Contact E-mail Address: V.M.Wolters@umcutrecht.nl

Introduction: Combining thiopurines with infliximab might reduce antibody formation against infliximab, but no paediatric data supporting this assumption are available yet.

Aims & Methods: Evaluation of the effect of concomitant immunomodulator use on formation of antibodies to infliximab (ATI) in paediatric patients with Crohn’s disease (CD) and the association of ATI appearance and loss of response. In this retrospective nationwide multicentre observational study we collected clinical and biochemical data of children diagnosed with CD treated with infliximab between 2009 and 2014. ATI formation was analysed with Chi-square test and time to ATI formation with Kaplan-Meier and log rank test. Loss of response was defined as need for either surgery or switch to other medical therapy than infliximab.

Results: In total, 229 children were identified (138 men, median 25 months on infliximab). Eighty-six patients (38%) received continuous combined immunosuppression (CCI) with infliximab, 115 patients (50%) early combined immunosuppression (ECI) (median 6.2 months), followed by infliximab monotherapy, and 28 patients (12%) infliximab monotherapy (IFX). Overall 25 of 229 patients (11%) developed ATIs: 6 on CCI (7%), 11 on ECI (10%) and 8 on IFX (29%) after respectively 6, 25, and 11 months (median). Antibodies were measured in 162 patients (70.7%). The incidence of ATI formation was higher in patients receiving IFX compared to CCI (p=0.006) and ECI (p=0.01), while no significant difference was found between CCI and ECI (log rank overall 0.004). Sixteen out of 25 patients (64%) developing ATIs had loss of response, versus 32 of 204 patients (16%) without ATIs (p=0.0001, log rank 0.01). When focusing on the group early combined immunosuppression, 10 out of 80 patients (12.5%) developed ATIs when receiving less than 12 months combination therapy, compared to 1of 35 (2.9%) patients receiving more than 12 months combination therapy.

	Concomitant immunomodulator use
<12 months	> 12 months
ATI, n (%)	10 (12.5)	1 (2.9)
Non-ATI, n (%)	70 (87.5)	34 (97.1)
Total	80	35

Conclusion: Combination therapy is superior to infliximab monotherapy as it significantly reduces antibody formation and loss of response in children with CD. Concerns about the lymphoproliferative risk of long-term use of thiopurines make that early combined immunosuppression for at least 12 months, followed by infliximab monotherapy, might be a safer and equally effective alternative to continuous combined immunosuppression.

Disclosure of Interest: None declared

P1005 CLINICAL REMISSION INDUCED BY EXCLUSIVE ENTERAL NUTRITION (EEN) IN PEDIATRIC CROHN'S DISEASE IS ASSOCIATED WITH MICROBIOME METABOLIC CHANGES TOWARD INCREASED XENOBIOTIC BIODEGRADATION AND METABOLISM

K. A. Dunn¹, J. Connors², B. MacIntyre², A. Stadnyk³, J. P. Bielawski¹, N. Thomas³, A. R. Otley², J. Van Limbergen²³

¹Dept of Biology, Dalhousie University, ²Division of Pediatric Gastroenterology & Nutrition, IWK Health Centre, ³Dept of Microbiology & Immunology, Dalhousie University, Halifax, Canada

Contact E-mail Address: johanvanlimbergen@dal.ca

Introduction: The mode of action of exclusive enteral nutrition (EEN) as induction therapy in pediatric Crohn's disease (CD), is proposed to involve changes in gut microbiome structure and function. Characterization of the microbiome has largely focused on the assessment of diversity and the identification of protective and disease-associated species.

Aims & Methods: Our aims were to compare microbial community structure and function in pediatric CD patients before and after induction of remission by EEN treatment. Community structure was assessed in terms of phylotypes, and function was assessed in terms of metabolic pathways.

Stool metagenomic sequences of 5 pediatric CD patients who underwent EEN treatment were obtained (MiSeq). Sequences were searched against the green genes database to obtain microbial composition profiles (using 16S rRNA genes). To obtain functional assignment, sequences were searched against 28 representative KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways and HUMAnN to assign function. Samples collected prior to EEN treatment were compared to samples collected after 4, 8 or 12 weeks of EEN treatment. All participants achieved clinical remission (PCDAI < 10) after 12 weeks of EEN. Microbial composition profiles were analyzed using QIIME and STAMP, and functional profiles were inferred using STAMP and BiomeNet.

Results: Changes in CD patient microbial community structure before and during EEN were variable. However, functional profiling of CD patient microbiota before and during EEN treatment revealed a significant increase in metabolic functions related to biodegradation and metabolism of xenobiotics, such as benzoate (p < 0.05). BiomeNet uncovered changes during weeks 4 and 8 of treatment consistent with large-scale changes in metabolic interactions at the community level. We observed associated changes in community diversity: a decrease and then increase in diversity over the course of EEN treatment. Metabolic potential generally increased at the same time as diversity decreased. This could be due to the metabolic repertoire of those species that were present (as inferred from enzyme encoding gene sequences). Bayesian modeling of metabolic structures via BiomeNet revealed that the therapeutic effect of EEN might be predicted by monitoring the change in community level metabolic structures over the course of treatment.

Induction of clinical remission by EEN was characterized by a distinct cycle of change in community level metabolic structure, and the microbiome of the one patient that experienced several severe flare-ups did not complete this cycle of change. This finding suggests that community metabolic function could be monitored for the purpose of determining if the duration of EEN was sufficient to maintain a flare free state. Alternatively, patients who complete the cycle quickly might discontinue EEN early.

Conclusion: The microbiome of CD patients is functionally altered during EEN treatment. Metabolic potential for xenobiotic biodegradation and metabolism increases during treatment, but then, after 12 weeks, it returns to a state very similar to pre-treatment and controls.

Disclosure of Interest: None declared

P1006 EFFECT OF EARLY VERSUS LATE AZATHIOPRINE TREATMENT IN PEDIATRIC ULCERATIVE COLITIS: DATA FROM THE ITALIAN REGISTRY FOR PEDIATRIC IBD

G. D'Arcangelo¹, M. Bramuzzo², M. Gasparetto³, M. Martinelli⁴, P. Alvisi⁵, M. T. Illiceto⁶, S. Valenti⁷, S. Pellegrino⁸, C. Catassi⁹, S. Arrigo¹⁰, S. Martelossi², S. Cucchiara¹, M. Aloi¹, on behalf of SIGENP

¹Pediatric Gastroenterology And Liver Unit, Sapienza University of Rome, Rome, ²Pediatric Gastroenterology, Institute for Maternal and Child Health IRCCS “Burlo Garofalo", Trieste, ³Pediatric Gastroenterology, University of Padua, Padua, ⁴Pediatric Gastroenterology, University of Naples “Federico II,", Naples, ⁵Pediatric Department, Maggiore Hospital, Bologna, ⁶diatric Gastroenterology and Endoscopy Unit, Spirito Santo Hospital, Pescara, ⁷Pediatric Gastroenterology and Endoscopy, ⁸ Pediatric Gastroenterology and Cystic Fibrosis, University of Messina, Messina, ⁹Department of Pediatrics, Università Politecnica delle Marche, Ancona, ¹⁰Paediatric Gastroenterology Unit, Institute “Giannina Gaslini”, Genoa, Italy

Contact E-mail Address: marina.aloi@uniroma1.it

Introduction: Thiopurines, 6-mercaptopurine and azathioprine (AZA), are the mainstay in maintenance therapy of pediatric ulcerative colitis (UC).

Aims & Methods: We aimed at describing the efficacy of AZA in newly diagnosed pediatric UC, comparing the outcomes of “early” (0-6 months) versus “late” (6-12 months) initiation of therapy.

Data from all children with UC treated with AZA within 12 months after the diagnosis and included in the SIGENP prospective, multicenter registry, were included. Corticosteroid (CS) free remission at 12 months was the primary outcome evaluated. The 2 groups were also compared for mucosal healing, need for treatment escalation, therapy-related adverse events and need for surgery at a 24-month follow-up.

Results: Of 401 children with a diagnosis of UC, 166 were treated with AZA within the first year of diagnosis. Seventy-one patients were excluded because of a follow-up shorter than 1 year, thus 95 were included for efficacy analyses (mean age 10.7 ± 3.8 years, 59% females). Fifty-four patients (57%) started AZA between 0–6 months (early), 41 (43%) after 6–12 months (late). Twenty-seven (51%) of the “early” patients were in CS-free remission at 1 year, compared to 24 (61.5%) of the “late” ones (p=0.39). Mucosal healing occurred in 26 (39%) of the 66 patients for whom data on mucosal inflammation at 1 year were available, no difference was found between the two groups (32% “early” versus 45% “late”; p=0.45). Serious adverse events occurred in 3 patients (2 fungal pneumonia, 1 pancreatitis), 2 in the “early” and 1 in the “late” group. Overall, mild side effects were recorded in 16 patients (17%; 5 leucopenia, 11 pancreatic enzyme elevation):10 in the “early” and 6 in the “late” group (p=0.78), 3 requiring AZA discontinuation. No difference was found for the need of treatment escalation, use of infliximab over time and rate of surgery.

Conclusion: Introduction of AZA within 6 months of diagnosis is not more effective than later treatment to achieve CS-free remission in pediatric UC. The rate of mucosal healing is not related to the timing of AZA initiation. Serious adverse events related to treatment are uncommon.

Disclosure of Interest: None declared

P1007 MONITORING MUCOSAL HEALING WITH FAECAL CALPROTECTIN IN CHILDREN WITH ULCERATIVE COLITIS

M. Meglicka¹, M. Szczepański¹, M. Dądalski¹, J. Kierkuś¹

¹Gastroenterology, Hepatology, Feeding Disorders and Paediatrics, The Children’s Memorial Health Institute, Warsaw, Poland

Contact E-mail Address: meglickam@gmail.com

Introduction: Faecal calprotectin (FC) is a good marker in monitoring mucosal healing in adults with ulcerative colitis. Its concentration in faeces is closely related to state of mucosa observed in endoscopy. There are a few studies concerning FC in mucosa status assessment in paediatrics population with inflammatory bowel disease.

Aims & Methods: The aim of the study was to assess the usefulness of FC as a biomarker of endoscopy proven mucosal healing in monitoring of children with UC. 81 patients with UC (F 43, M 38, ±14.04 years) were involved to the study and had elective colonoscopy performed, FC level and erythrocyte sedimentation rate (ESR) within a week before endoscopy measured. Each patient had also body mass index (BMI) and paediatric ulcerative colitis activity index (PUCAI) calculated. Mucosa status during endoscopy was assessed with Baron score. Full mucosal healing was defined as Baron score=0. We have identified two subgroups: those with full mucosal healing, and patients with inflamed gut mucosa. The receiver operating characteristic curve (ROC ) was used as a statistical method to establish cut-off points. The cut-off points are calprotectin threshold for simple model and posterior probability threshold for the linear discriminant analysis (LDA). The area under the curve (AUC) assesses the differentiation quality of the study group based on the model score. To increase sensitivity at high specificity the LDA with FC, ESR, BMI and PUCAI was taken.

Results: AUC for the simple model was 0.86. The selected cut-off level of discrimination between subgroup with full mucosal healing vs. subgroup with mucosal inflammation present was 274 μg/g with sensitivity 0.97 and specificity 0.62. When specificity was outweighed over sensitivity the cut-off point was 37 μg/g with sensitivity 0.32 and specificity 0.94. Due to the low sensitivity accompanying high specificity we used LDA with other parameters to increase sensitivity rate. With LDA used on FC, ESR, BMI and PUCAI the AUC was 0.88, and we could discriminate our patient with sensitivity 0.53 and specificity 0.96.

Conclusion: FC is a good marker of mucosal healing in monitoring of children with UC. FC above 274 μg/g enable to select 62% of patients with active inflammation in gut mucosa. LDA with FC, ESR, BMI and PUCAI let us select 53% of patients with full mucosal healing. Using these two methods, step by step, we could discriminate patients with unknown mucosa status, that requires endoscopy.

Disclosure of Interest: None declared

P1008 REMISSION INDUCTION IN CORTICOSTEROID-NAÏVE CHILDREN AND ADOLESCENTS WITH ACTIVE ULCERATIVE COLITIS BY ADSORPTIVE LEUCOCYTAPHERESIS AS MONOTHERAPY OR IN COMBINATION WITH LOW-DOSE PREDNISOLONE AFTER FAILURE OF FIRST-LINE MEDICATIONS

T. Tanaka¹, T. Iiboshi¹, H. Goishi¹, M. Akagi¹, T. Kajihara¹, T. Miura¹

¹Gastroenterology, Akitsu Prefectural Hospital, Hiroshima, Japan

Contact E-mail Address: tomotaka@c.do-up.com

Introduction: Given that patients with active ulcerative colitis (UC) have elevated and activated myeloid lineage leucocytes including the CD14 + CD16+ monocyte phenotype known to release tumour necrosis factor-α, selective depletion of myeloid leucocytes by adsorptive granulocyte/monocyte apheresis (GMA, Adacolumn) should promote remission, or enhance drug efficacy. This strategy is most relevant in paediatrics and adolescents in whom corticosteroids raise safety concerns.

Aims & Methods: This study was to evaluate the efficacy of GMA in children and adolescents with active UC in whom conventional first-line medications had failed. In a single centre setting, between 2010 and 2014, a total of 28 consecutive children and adolescents, age 11-19 years, body weight 33-55kg were given mesalazine (n=21) or sulphasalazine (n=7) as a first-line medication. Twenty patients relapsed or did not respond and received GMA with the Adacolumn, 2 sessions in the first week, then weekly, up to 11 sessions. Patients who achieved a decrease of ≥5 in the clinical activity index (CAI) continued with GMA, while non-responders received 0.5 to 1.0 mg/kg/day prednisolone plus additional GMA sessions. At entry and week 12, patients were clinically and endoscopically evaluated, allowing each patient to serve as her (or his) own control.

Results: At entry, all 28 patients were corticosteroid naïve and none had deep colonic UC lesions together with extensive loss of the mucosal tissue at the affected sites. Eight patients achieved remission with the first-line medications and did not receive GMA. Six patients did not respond well to the first 5 GMA sessions and received prednisolone plus GMA, while 12 patients responded to the first 5 GMA sessions and received additional sessions and 2 withdrew. At entry, the average CAI was 14.2 ± 0.4, range 11-17, and the average endoscopic index was 9.2 ± 0.4, range 7-11. The corresponding values at week 12 were 2.1 ± 0.2, range 1-4 (P < 0.001) and 2.4 ± 0.2, range 1-4 (P < 0.001). Prednisolone was tapered to 0mg within 3 months. Therefore, at week 12, all 26 patients had achieved clinical remission, majority with mucosal healing (complete remission). No serious adverse event associated with GMA was observed.

Conclusion: GMA in patients with deep ulcers and extensive loss of the mucosal tissue (a major GMA non-responder feature) has not been associated with significant efficacy. In this study, GMA in young corticosteroid naïve patients with active UC refractory to the first-line medications was associated with clinical remission and mucosal healing, while in non-responders to GMA monotherapy, addition of a low dose prednisolone enhanced the efficacy of GMA and tapering of prednisolone was not associated with UC relapse. Therefore, the majority of young steroid-naïve UC patients who fail to respond to the first-line medications should respond well to GMA and avoid pharmacologicals.

Disclosure of Interest: None declared

TUESDAY, OCTOBER 27, 2015   09:00-17:00

OTHER LOWER GI DISORDERS II – HALL 7__________

P1010 CLOSTRIDIUM DIFFICILE INFECTION: COMPARISON OF DIAGNOSTIC TESTS AND CHARACTERIZATION OF STRAINS

E. G. Vilela¹, G. G. L. Cancado², R. O. S. Silva³, F. C. F. Lobato³

¹Internal Medicine, ²Instituto Alfa de Gastroenterologia, ³Laboratorio de Anaerobio, Federal University of Minas Gerais, Belo Horizonte, Brazil

Contact E-mail Address: evilela@medicina.ufmg.br

Introduction: Clostridium difficile is an anaerobic gram-positive, spore-forming, toxin-producing bacillus, which cause illnesses ranging from mild diarrhea to fulminant colitis. Laboratory diagnosis largely relies on rapid toxin detection kits through immunoenzymatic assays (ELISA), although this diagnostic approach has recently been called into question. The incidence of C. difficile infection has markedly increased in the last years, notably with the epidemic spread of the binary toxin producer ribotype 027.

Aims & Methods

Aims: to compare the performance of commercial ELISA kits versus cytotoxicity (CTA) and toxigenic culture (TC) assays for the diagnosis of CDI in Brazil. Furthermore, isolate and characterize, genotypically and phenotypically, the C. difficile strains.

Methods: Ninety six fecal samples were obtained and analyzed between January and November 2014 from inpatients admitted to Hospital das Clínicas of Universidade Federal de Minas Gerais in Belo Horizonte, Brazil. All patients were under broad-spectrum antibiotic therapy and the samples were collected during active diarrhea episodes. All samples were tested for the presence of toxins A/ B by the following commercial ELISA kits: C. difficile Tox A/B II (Techlab Inc., USA), Remel ProSpecT C. difficile Toxin A/B (Oxoid, UK), and Ridascreen C. difficile toxins A/B (R-Biopharm, Germany). Cytotoxicity assays were performed using Vero cells. Stool samples were also cultured and all colonies with suggestive morphologies were subjected to a multiplex-PCR protocol involving a housekeeping gene (tpi), toxins A (tcdA) and B (tcdB), and a binary toxin gene (cdtB). All strains positive for tcdA or/and tcdB were considered toxigenic. C. difficile isolates were analyzed by PCR-ribotyping. Minimal inhibitory concentration for metronidazole (MTZ) and vancomicyn (VAN) was determined.

Results: From the 96 sampled patients, 25 (26%) were positive according to CTA. C. difficile was isolated from 29 (30.2%) samples, of which six isolates were considered non-toxigenic and 23 (24%) were toxigenic according to PCR. The kappa concordance between TC and CTA was 0.71 (0.51-0.9). Of these patients, 15 (65.2%) were A + B + CDT-, six (26.1%) were A + B + CDT+, and two (8.7%) were A-B + CDT-. Nine PCR-ribotypes were identified among the isolates, three unpublished (SLO 197, 198 and 199). PCR-ribotype 027 was not detected. The three ELISAs exhibited sensitivities between 64 and 68% and specificities greater than 94%. All strains were susceptible to MTZ and VAN.

Conclusion: It is essential to have accurate laboratory diagnosis of C. difficile infection to ensure patients receive appropriate treatment. Furthermore, the detection and isolation of genes related to virulence factors in C. difficile strain can aid the understanding of risk factors and epidemiology of disease. Despite not having been detected the presence of ribotype 027, some strains, including those three not previously described, had the gene of the binary toxin, resulting in potential increased of the virulence. There were no strains resistant to conventional therapy, although the therapeutic success can also be influenced by other factors, such as the intestinal microbiota.

Disclosure of Interest: None declared

P1011 HEALTHY BUT NOT TUMOR TISSUE-DERIVED CELL-FREE DNA NEUTRALIZES THE ACTIVATION OF HUMAN MONOCYTES

I. Furi¹², A. Kalmar¹, A. Scholler³⁴, G. Valcz²⁴, B. Wichmann²⁴, B. K. Bartak⁴, B. Molnar²⁴, Z. Tulassay²⁴

¹2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary, ²Molecular Medicine Research Unit, Hungarian Academy of Sciences, ³2nd Department of Surgery, ⁴2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary

Contact E-mail Address: furiistvan88@gmail.com

Introduction: Bacterial ligands (LPS) and self-DNA sequences are recognized by TLRs on human immune competent cells. Cell-free DNA sequences with unmethylated CpG dinucleotide motifs may be a possible non-specific immune system stimulants by the mechanism of supression the function of the Treg cells and the re-activation of anti-tumor immunity.

Aims & Methods: We compared the immunostimulatory effect of LPS (from E.coli) and cell free DNA originated from normal and tumor colonic tissue on isolated peripheral mononuclear cells (PBMCs) from healthy volunteers.

DNA isolation was performed from fresh-frozen surgically removed colonic samples. PBMC were donated by healthy volunteers and isolated by Ficoll-Hypaque (Sigma-Aldrich). The viability of PBMCs was determined by Trypane blue dying. PBMCs were incubated for 24 hours with 10 µg of DNA either from normal and tumor origin. After the incubation we performed the treatment with normal and tumor tissue derived DNA (TLR9 agonists) in or without the combination with LPS (TLR4 agonist) As a next step Affymetrix U133 2.0 whole-genome expression analysis was performed from the isolated total RNA.

Results: Affymetrix whole-genome microarray results reflect a massive monocyte activation of the LPS treatment through the overexpression an early phase pro-inflammatory cytokine IL-6, monocytic marker CD163, and other chemokines (CXCL1, CXCL5). We also observed an increased IFNG and IL-10 expression in PBMCs after LPS treatment. Dual activation of TLR4 and TLR9 (co-administration of tumor or healthy tissue tissue DNA and LPS) has resulted a different effect on the gene expression. Healthy tissue derived DNA and LPS co –treatment induced down-regulation of TLR4, IRG1 CXCL6, CXCL9 and CCL13.

Conclusion: LPS treatment induced a massive activation of monocytes, which could be neutralized by the co-administration of healthy tissue derived cell-free DNA through the down-regulation of the sensing receptor and response genes. We reflected the antagonism between TLRs and the possible non.-inducible effect of tumor tissue derived cell free DNA on immune competent cells through TLR9.

Disclosure of Interest: None declared

P1012 STIMULATION OF TOLL-LIKE RECEPTOR 7 ATTENUATES EPITHELIAL BARRIER DYSFUNCTION DURING COLITIS IN MICE

J. Estevez¹, V. Martinez¹

¹Department of Cell Biology, Physiology and Immunology, Universitat Autonoma de Barcelona, Bellaterra, Spain

Contact E-mail Address: javier.estevez@uab.cat

Introduction: Altered epithelial barrier function (EBF) and deregulation of mucosal immune responses are common in intestinal inflammatory disorders. Activation of innate immunity-dependent mechanisms, including those mediated by Toll-Like receptors (TLR), has immunomodulatory activity with beneficial effects in colitis.

Aims & Methods: We assessed if TLR7 participates in the modulation of EBF during states of intestinal inflammation. Colitis was induced in CD1 male mice by exposure to dextran sodium sulfate (DSS; 5 % in the drinking water, for 5 days). EBF was determined assessing the permeability to macromolecules (4 kDa fluorescein isothiocyanate–dextran, FD4) in vitro (apical-to-basolateral flux FD4 in an Ussing chamber system) and in vivo (passage of intracolonic FD4 to blood and urine). Potential modulatory role of colonic TLR7 on EBF was assessed by local stimulation of the receptor with the selective agonist imiquimod (IMQ). Changes in gene expression of tight junction-related proteins (occludin, claudin 2, claudin 3, Zona Occludens-1) and barrier-related markers (proglucagon and myosin light-chain kinase) were assessed by RT-qPCR.

Results: Exposure to DSS lead to a state of colitis, as evidenced macro and microscopically. In colitic animals the passage of FD4, as assessed either in vitro or in vivo was increased, thus indicating an altered EBF. In in vitro conditions, stimulation of TLR7 with IMQ in inflamed tissues (300 µg, apical or basolateral) restored the epithelial permeability to FD4 to basal levels (Table). Similarly, in in vivo conditions, intracolonic IMQ (300 µg/mice) attenuated the passage of FD4 to blood and urine in colitic mice, thus indicating a partial restoration of EBF (Table). In DSS-treated animals, expression of tight junction-related proteins and barrier related factors was down regulated (50-70% vs. non-inflamed animals). Local stimulation of TLR7 with IMQ did not revert these effects.

Abstract number: P1012 Table.

Effects of inflammation and IMQ on EBF.

			Non inflamed		Inflamed
	Vehicle	IMQ	Vehicle	IMQ
In vitroFlux of FD4 (% in 60 min)		Basolateral vehicle/IMQ	0.0016 ± 0.0005	0.0009 ± 0.0004	0.0031 ± 0.0008*	0.0024 ± 0.0009
	Apical vehicle/IMQ	0.0018 ± 0.0005	0.0010 ± 0.0002	0.0041 ± 0.0010*	0.0019 ± 0.0005#
In vivo		FD4 in serum (µg/mL)	2.03 ± 0.33	1.89 ± 0.17	15.88 ± 7.25*	7.89 ± 2.60*
	FD4 in urine (µg/mL)	8.68 ± 1.79	12.53 ± 1.51	155.80 ± 36.57**	84.12 ± 24.03*

Data are mean ± sem, n=4-10; #: P < 0.05 vs. Inflamed-vehicle; **: P < 0.01, *: P < 0.05 vs. non-inflamed vehicle, respectively.

Conclusion: Stimulation of TLR7 leads to an improvement of inflammation-induced altered EBF. The mechanisms mediating these actions seem to be independent of the modulation of tight junction-related proteins and barrier modulators. TLR7-mediated innate immune responses might regulate EBF with a defensive function, preventing the passage of luminal factors and, therefore, reducing antigens exposure and the development of exacerbated immune responses and intestinal inflammation.

Disclosure of Interest: None declared

P1013 ABDOMINAL TUBERCULOSIS – 10 YEAR EXPERIENCE FROM A UK DISTRICT GENERAL HOSPITAL

M. Ford¹

¹The Dudley Group NHS Foundation Trust, Dudley, United Kingdom

Contact E-mail Address: markford@doctors.net.uk

Introduction: The rate of tuberculosis has remained relatively stable over the past decade; however the proportion of cases with extra-pulmonary disease has increased from 40.9% to 47.9%. Multiple studies have shown that diagnosis of abdominal tuberculosis (ATB) is often delayed due to non-specific symptoms in patients. The aim of this study was to examine a selection of patients from a UK district general hospital with a diagnosis of ATB and the process in which that diagnosis was reached.

Aims & Methods: We performed a retrospective review of all patients at Russells Hall Hospital, Dudley, who had a diagnosis of ATB between 2004 and 2014. Demographic, clinical, laboratory and radiographical findings were collated including the time delay between hospital presentation and diagnosis.

Results: Sixteen cases of ATB were identified with a median age of 38.5 years at time of diagnosis (range 22-73 years) and a male/female split of 56% and 44% respectively. The majority (87.5%) were of non-white background; South Asian (69%), Afrocaribbean (19%) and White British (12%). The commonest features were abdominal pain (62.5%), weight loss (50%) and fevers (50%). The time between first presentation to hospital and diagnosis ranged from 2 days to 3 years. Basic investigations revealed mean haemoglobin of 11.9 g/dL (SD 1.70), CRP of 109 mg/L (SD 91.81), Alkaline phosphatase of 200 IU/L (SD 159.32), and albumin of 37.1 g/L (SD 6.54). The chest x-ray was normal in 11 patients and of the remaining abnormalities included consolidation in 3 patients, cavitating lesion in 1 patient, and the final patient did not have an x-ray. There was a wide range of sites of disease including small bowel (25%), peritoneum (25%), lymph nodes (18.75%), appendix (12.5%), liver (12.5%) and omentum (6.25%). Tuberculin test was only performed in three patients and all of which were positive. Diagnosis was based on either histology (43.75%), imaging (31.25%), microbiology (6.25%), or a combination of clinical suspicion and imaging or appearances at surgery (18.75%). The majority who received treatment (9/14) were given Rifater plus ethambutol. The remaining five patients all received a different combination of antituberculous treatment (Rifater alone, Rifinah ± Pyrazinamide and Ethambutol, Rifampicin/Isoniazid/Pyrazinamide ± Ethambutol). Two patients did not receive treatment as their diagnosis was made post-mortem. Of the sixteen patients, ten were treated and discharged, three died, two have on going review and one was lost to follow up.

Conclusion: ATB is a difficult diagnosis to make and there can be a significant time delay between symptom onset and diagnosis as the symptoms can be varied and insidious in nature. It is an easily treatable condition and a combination of abdominal pain, fevers and/or weight loss in a non-Caucasian patient should warrant further investigation.

Disclosure of Interest: None declared

P1014 TUMOUR BUDDING WITH AND WITHOUT ADMIXED INFLAMMATION: TWO DIFFERENT SIDES OF THE SAME COIN?

N. Max¹, L. Harbaum², M. Pollheimer³, R. Lindtner⁴, P. Kornprat⁵, C. Langner¹

¹Pathology, Medical University of Graz, Graz, Austria, ²Oncology, Haematology, BMT with Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, ³Pathology, University of Graz, Graz, ⁴Surgery, Medical University of Innsbruck, Innsbruck, ⁵Surgery, Medical University of Graz, Graz, Austria

Contact E-mail Address: cord.langner@medunigraz.at

Introduction: In colorectal cancer, the morphology at the invasive tumour margin is known to reflect the biology of disease, rendering important prognostic information. Tumour budding, defined as the presence of isolated single cells or small clusters of cells (composed of fewer than five cells), has been associated with adverse outcome. In contrast, peritumoural inflammation has been associated with favourable outcome. Of note, the antitumour activity of inflammation may lead to the destruction of tumour glands and, ultimately, the presence of small clusters of cells scattered in the tumour stroma (“pseudo-budding”). Our study aimed to analyse the relationship between tumour budding and inflammation and its possible prognostic significance in a large cohort of colorectal cancer patients.

Aims & Methods: Tumours of 381 randomly selected patients were retrospectively reviewed for the extent of tumour budding, with high-grade budding reflecting presence of 10 or more budding fociscattered at the invasive tumour margin. The intensity of the peritumoral inflammation was assessed using a four-degree scale according to Klintrup-Mäkinen criteria. Progression-free and cancer-specific survivals were determined using the Kaplan-Meier method.

Results: Overall, 221 (58%) tumours showed low grade, 160 (42%) tumours high-grade budding. 167 (44%) tumours showed no increase or only a mild and patchy increase of inflammatory cell sat the invasive tumour margin, but no destruction of invading cancer cell islets (scores 0-1), whereas in 214 (56%) tumours a band-like infiltrate of inflammatory cells with at least some destruction of cancer cell islets was seen (scores 2-3). When analysis was restricted to tumours with high-grade budding, 82 (51%) cases showed mild inflammation (scores 0-1) and 78 (49%) marked inflammation (scores 2-3). Tumour budding was significantly associated with both progression-free and cancer-specific survival in our cohort. Cases with high-grade budding and marked inflammation had a better outcome regarding progression-free (p < 0.001) and cancer-specific survival (p < 0.001) than high-grade cases with only mild inflammation. Outcome in these cases, however, was still worse compared to cases with low-grade budding, in which the extent of peritumoral inflammation had no further prognostic effect.

Conclusion: Though tumours with marked inflammation at the invasive tumour margin may showd estruction of cancer islands due to the anti-tumour effect of the inflammatory infiltrate(“pseudo-budding”), the presence of isolated tumour cells and small clusters of cells scattered in the stroma at the tumour margin does not per se imply favourable outcome in these cases. It is of note that tumours with high-grade budding and marked inflammation at the invasion front still bear a significantly poorer outcome than tumours with low-grade budding, in which the extent of peritumoural inflammation had no prognostic effect.

Disclosure of Interest: None declared

P1015 ADMINISTRATION OF ANTI-INTERLEUKIN-6 ANTIBODIES AMELIORATES CAECAL LIGATION AND PUNCTURE-INDUCED GASTROINTESTINAL MOTILITY DISTURBANCES AND COLONIC PERMEABILITY CHANGES

S. Nullens¹, M. Staessens¹, C. Peleman¹, S. Francque², C. Lammens³, S. Malhotra-Kumar³, J. De Man¹, B. De Winter¹

¹Lab Experimental Medicine and Paediatrics - Gastroenterology, University of Antwerp, Antwerp, ²Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, ³Lab of Medical Microbiology, University of Antwerp, Antwerp, Belgium

Contact E-mail Address: sara.nullens@uantwerpen.be

Introduction: Sepsis represents a significant burden of disease and mortality in Intensive Care Units. Ileus, the inhibition of the propulsive motility of the gastrointestinal (GI) tract, together with mucosal barrier dysfunction, will maintain sepsis by the translocation of bacteria and luminal antigens. Interleukin-6 (IL-6) is a major proinflammatory cytokine that is secreted by immune cells such as macrophages and T cells. In previous experiments, we observed a significant increase in systemic and colonic IL-6 levels that coincided with an increase in colonic permeability.

Aims & Methods: We aimed to investigate the effect of anti-IL-6-antibodies on ileus, colonic permeability and translocation of intestinal bacteria in blood in a septic mouse model. Sepsis was induced in Swiss-OF1 mice by caecal ligation and puncture (CLP). Sham-operated animals served as controls. Mice received either one injection of anti-IL-6 antibodies 1 mg/kg i.p. (anti-IL6) or the IgG isotype control (IgG) jointly with the CLP procedure (n = 8-12/group). Occurrence of ileus was confirmed 48h post-procedure by studying the geometric center (GC) of beads. In the permeability study, mice were anesthetized and underwent a laparotomy, during which the colon was ligated and injected with 100 µL of a 9% Evans blue (EB) solution. Mice were sacrificed 1h later via cardiac puncture, and serum samples as well as homogenized colon supernatants were analyzed for IL-6 levels. Colons were rinsed and incubated for 24h in formamide to extract the EB from the colon wall. Whole blood was plated directly onto agar plates and cultured for 24h to quantify bacterial translocation.

Results: CLP-induced sepsis significantly delayed GI transit and this effect was reversed by anti-IL-6 treatment (GC: sham + IgG 5.4 ± 0.4, sham + anti-IL6 5.8 ± 0.4, CLP + IgG 2.6 ± 0.4*, CLP + anti-IL6 4.3 ± 0.5). Serum and colonic IL-6 levels rose significantly following CLP, and anti-IL6 was able to reduce them (serum: sham + IgG 4.6 ± 2.5, sham + anti-IL6 2.0 ± 0.6, CLP + IgG 276.6 ± 71.6, CLP + anti-IL6 84.5 ± 18.3 pg/mL, p < 0.05 for the effect of CLP and of anti-IL6; colon: sham + IgG 3.8 ± 2.4, sham + anti-IL6 2.2 ± 0.8, CLP + IgG 209.8 ± 94.6, CLP + anti-IL6 52.3 ± 14.1 pg/100 mg colonic tissue, p < 0.05 for the effect of CLP). CLP-induced sepsis significantly increased colonic permeability. The impaired barrier was improved by anti-IL6 treatment (sham + IgG 22.6 ± 1.7, sham + anti-IL6 29.3 ± 2.2, CLP + IgG 52.9 ± 10.4*, CLP + anti-IL6 27.8 ± 5.5 µg EB/100 mg colon). Finally, anti-IL6 numerically reduced the number of positive blood cultures in septic animals (sham + IgG 0/6, sham + anti-IL6 0/8, CLP + IgG 7/9, CLP + anti-IL6 5/9 positive cultures, Pearson's Chi-squared test p < 0.05 for CLP + IgG or CLP + anti-IL6 versus sham + IgG).

Conclusion: CLP caused a marked delay in GI transit with an increased colonic permeability and subsequent increased risk of bacterial translocation. Anti-IL-6 treatment significantly ameliorated GI motility, suppressed inflammation and normalized the permeability of the colonic wall. We conclude that the proinflammatory cytokine IL-6 has a major influence on colonic permeability and GI motility disturbances following CLP-induced septic ileus.

Disclosure of Interest: None declared

P1016 CONTIUOUS STIMULATION WITH CYTOKINES LEADS TO IRREVERSIBLE ACTIVATION OF NF-κB SIGNALING IN COLONIC EPITHELIAL CELLS BY ORGANOID CULTURE

S. Hibiya¹, K. Tsuchiya¹, T. Shirasaki¹, K. Fukushima¹, R. Hayashi², N. Horita¹, S. Oshima¹, R. Okamoto³, T. Nakamura⁴, M. Watanabe¹

¹Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, ²Gastroenterology and Metabolism, Hiroshima University, Hiroshima, ³Center for Stem Cell and Regenerative Medicine, ⁴Advanced Therapeutics for Gastrointestinal Diseases, Tokyo Medical and Dental University, Tokyo, Japan

Introduction: The patients with ulcerative colitis are at increased risk of developing colitis-associated cancer, suggesting that contiuous inflammation in colon leads to the development of carcinogenesis. However, the mechanism of the carcinogenesis in colitis-associated cancer remains unknown. Recently, 3-dimentional (3D) primary organoid culture of colonic epithelial cells has been established in our group (Nature Medicine 2012).

Aims & Methods: We therefore aimed to assess the influence of continuous stimulation with cytokines on colonic epithelial cells in vitro, using 3D primary organoid culture.

Colonic crypts were isolated from 8-week old female mouse and were cultured by TMDU method. To mimic chronic inflammation, the mixture of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), lipopolysaccharide (LPS) and flagellin were added into the medium every other day. Microarray analysis was performed after 60 weeks of cytokines stimulation. Gene Set Enrichment Analysis (GSEA) was also performed for the detection of specific cell signaling pathway. The expression of NF-κB target genes IL-8, DUOXA2 was assessed by quantitative RT-PCR. For the analysis of accumulation of NF-κB p65 in nuclei, 3D immunohistochemistry of whole organoid was performed by stain with anti-NF-κB p65 antibody. To evaluate reactive oxygen species (ROS) in live organoids, CellROX® Deep Red Stress Reagents (Life technologies) was added to medium for one day. Organoids were visualized by confocal laser fluorescent microscopy.

Results: The stimulation with TNF-α, IL-1β, IL-6, LPS and flagellin showed the significant induction of NF-κB target genes in colonic organoids. Microarray analysis with GSEA analysis showed significant induction of NF-κB signaling after 60 weeks of cytokines stimulation. Interestingly, the expression of DUOXA2 gene, which was NF-κB target genes and upregulated in microarray analysis, was gradually increased by the continuous stimulation with cytokine mixtures, suggesting that NF-κB signaling might be accumulated by the stimulating time. 3D immunostaining analysis showed that NF-κB p65 was accumulated in nuclei by longer time of the stimulation, indicating that continuous stimulation with cytokines might lead to a stronger activation of NF-κB signaling. Interestingly, accumulated NF-κB signaling by long-term stimulation remained active after the removal of all cytokines, whereas NF-κB signaling induced by short-term stimulation was completely shut down by the removal of all cytokines. ROS analysis showed that ROS were induced by stimulation with cytokines. Moreover, ROS in the organoid with long-term stimulation remained at 11 weeks after the removal of cytokines, suggesting that oxidative stress in the organoid with long-term stimulation was also irreversible.

Conclusion: Persistent inflammation leads to irreversible NF-κB signaling activation in colonic epithelial cells, suggesting that ”signal spiral” might be crucial for the carcinogenesis of colitis-associated cancer.

Disclosure of Interest: None declared

P1017 THE DISTURBANCE OF CENTRAL DOPAMINERGIC NEURONS IN RAT MODEL OF PARKINSON'S DISEASE INCREASES SUSCEPTIBILITY TO COLONIC INFLAMMATION

T. Chervinska¹, K. Nesteruk¹, A. Pryisiazhniuk¹, T. Dovbynchuk¹, B. Kopiak², L. Pelyukh¹, N. Nurishchenko¹, T. Sergeychuk¹, O. Kabanov¹, L. Garmanchuk¹, V. Sagach², G. Tolstanova¹

¹Educational-Scietific Center “Institute of Biology, Taras Shevchenko National University of Kiev, ²Bogomolets Institute of Physiology NASU, Kiev, Ukraine

Contact E-mail Address: gtolstanova@gmail.com

Introduction: The development of colonic inflammation in experimental colitis is associated with increase of the blood-brain barrier permeability and the loss of central dopaminergic neurons [1]. From the other hand, the disturbance of central dopaminergic neurons during Parkinson’s disease (PD) is characterized by colonic constipation [2]. Constipation might be associated with the growth of pathogenic microflora as a result of that the disruption of intestinal barrier integrity, inflammation development and further exacerbation of PD symptoms.

Aims & Methods: The aim of the present study was to check whether the colonic inflammation is primary associated with the early stages of PD pathogenesis or PD increases the susceptibility to colonic inflammation development. Study was done on male Wistar rats (180-250 g). Model of experimental PD was induced by single unilateral 6-hydroxydopamine (6-OHDA) administration, rats were enrolled in study 1 month after. Colonic inflammation was induced by 6% iodoacetamide enema. Levels of spontaneous and carbachol-stimulated colon motility was estimated by ballonographic method in vivo; the activity of Mg²⁺, Ca²⁺-ATPase and K⁺-ATPase in colonic smooth muscles - by the release of inorganic phosphate; colonic levels of calmodulin – by Western blot; the parietal microflora - by bacteriological culture methods; colonic endothelial permeability - by Evans blue extravasation; levels of inflammation - by colon myeloperoxidase activity (MPO), levels of IСAM-1 and arginase activity in peritoneal macrophages.

Results: 6-OHDA lesioned-rats had decreased tonic indexes of spontaneous and stimulated colon motility by 11.3 (p < 0.05) and 22.5% (p < 0.01); increased frequency of contractions of spontaneous (by 31.6%, p < 0.05) but not stimulated motility; increased amplitude of contractions (by 31.16%, p < 0.01) and decreased motor-activity index of stimulated colon motility (19.9%, p < 0.05) vs sham-lesioned rats. Delayed in colon motility in 6-OHDA rats was associated with increased colon level of Mg2+, Ca2+-ATPase activity (39.7%, p < 0.05), decreased K+-ATPase activity (17.0%, p < 0.05) & level of calmodulin (p < 0.05). Colon and ileum parietal microflora composition were not changed between sham & 6-OHDA-lesioned rats. It was no difference in the colonic mucosa endothelial permeability & ICAM-1 levels as well. While 6-OHDA rats had 2.3-fold depleted peritoneal macrophages functional reserve (p < 0.05). 6-OHDA rats were more predisposed to iodoacetamide-induced colonic inflammation vs sham-lesioned rats: MPO activity was higher 2.6-folds (p < 0.05); colonic endothelial permeability – 1.5-folds and IСAM-1 levels 5.5-folds (p < 0.05).

Conclusion: The delayed colonic motility is an early feature of experimental PD which is associated with low grade systemic inflammation. We showed for the first time that disturbance of central dopaminergic neurons in rat model of PD increases susceptibility to colonic inflammation development.

Disclosure of Interest: None declared

P1018 ADAPTIVE IMMUNE RESPONSES TRIGGERED BY HERPES SIMPLEX VIRUS TYPE 1 CAUSE ENTERIC NERVOUS SYSTEM DYSFUNCTION

V. Russo¹, I. Castagliuolo¹, L. Spagnol¹, V. Caputi², C. M. Giron², P. brun¹

¹Molecular Medicine, ²Pharmacological Science, University of Padova, Padova, Italy

Contact E-mail Address: venera.russo.1@studenti.unipd.it

Introduction: Anomalies of the enteric nervous system (ENS) have been associated to motility and inflammatory disorders of the gut. Since enteric neuropathies are characterized by various histopathological pictures including loss of ganglion cells or infiltrating mononuclear cells an immune-mediated damage, possibly triggered by an infectious agent, has been postulated. Indeed, we have recently shown in rodents that following intragastric (IG) administration the neurotropic Herpes simplex virus (HSV)-1 can infect the ENS resulting in time-dependent intestinal neuromuscular abnormalities¹. Therefore, we aimed to investigate whether adaptive immune responses are involved in the onset of ENS dysfunction following HSV-1 infection.

Aims & Methods: Male C57/Bl6 (WT) mice were inoculated intranasally with HSV-1 (10² pfu) and 4 weeks (W) later IG (10⁷ pfu). Starting 4 W after viral IG inoculum a group of mice received anti-CD8 antibody. Six-ten W after viral IG inoculum we: a) determined gastrointestinal (GI) motility by measuring fluorescein-isothiocyanate dextran distribution; b) assessed ENS integrity by immunohistochemistry on ileal whole-mount preparations; c) characterized the lymphocytes infiltrating the longitudinal muscle myenteric plexus (LMMP) and their reactivity to HSV-1 antigens by FACS analysis; d) quantified changes in isometric muscle tension following electric field stimulation (EFS) of ileal segments. To verify the role of lymphocytes in HSV-1 induced ENS dysfunction, CD3+ cells were isolated from the LMMP of mice 8-10 W after viral IG inoculum, in vitro pulsed with HSV-1, and injected in recipient mice. After one week the effects on isometric muscle tension following EFS stimulation of ileal segments were determined.

Results: At 8 and 10 W after IG inoculum, HSV-1 caused a significant delay in GI transit, impaired cholinergic neuromuscular transmission (p<0.01 vs control mice), altered expression and distribution of the neurofilaments peripherin and βIII-tubulin, whereas no anomalies were observed at 6 W after IG inoculum. In the LMMP, but not in the spleen, we observed an increase in CD3+ lymphocytes starting at 6 W and persisting up to 10 W after viral IG inoculum. At 8 W after viral IG inoculum HSV-1 reactive CD3⁺CD4⁺IL4⁺ and CD3⁺CD8⁺INF-γ⁺ were demonstrated in LMMP, whereas at 10 W non-HSV-1 specifically activated CD8+ T-cells were present in LMMP. Depletion of CD8+ T-cells, by administration of monoclonal anti-CD8 antibody, abolished the ENS damage and the neuromuscular anomalies observed at 8 W after viral IG inoculum. Ileal muscle tension was significantly altered (p<0.01 vs control) in recipient mice receiving in vitro HSV-1 pulsed LMMP lymphocytes isolated at the 8^th W post IG viral inoculum. Instead, the adoptive transfer of lymphocytes from 10 W infected mice resulted in dysmotility with or without in vitro exposure to viral antigens.

Conclusion: At different time points following infection of the ENS, HSV-1 activates lymphocyte subsets directly causing intestinal neuromuscular dysfunction. We speculate that HSV-1 infection of the ENS, as opposite to the central nervous system compartment, triggers adaptive immune responses that can alter the structure and the integrity of the neurons thus predisposing to bowel anomalies.

Disclosure of Interest: None declared

P1019 NO ASSOCIATION BETWEEN LACTASE 13910 POLYMORPHISM AND COLORECTAL POLYPS ANDCARCINOMA

G. Gencdal¹, E. Faralyalı¹, Ö. Özütemiz¹, U. S. Akarca¹

¹Gastroenterology and Hepatology, Ege University School of Medicine, İzmir, Turkey

Contact E-mail Address: gencogencdal@yahoo.co.uk

Introduction: Primary lactase deficiency ( PLD) affects more than the half of the world's population. LCT-13910 polymorphism was described and being widely used for diagnosis of PLD. The relationship between LCT-13910 polymorphism and risk for colorectal cancer is unclear.

Aims & Methods: We investigated the presence of a relationship between lactase deficiency and colon cancer and adenomatous polyps of the colon in our population. 166 patients (M:103; Mean Age: 60.7 ± 10.4 ), who had undergone total colonoscopy were included in the study. Anticoagulated blood was drawn from the patients following colonoscopy for genetic analyses (LCT-13910).

Results: The CC genotype in lactose gene 13910 locus, which was accepted as the genetic indicator of lactase deficiency, was determined as 83.7%. The CC genotype rate was determined as 89.1% in patients who had the history of milk intolerance and 81.5% in those with a history without milk intolerance (p=0.236). No difference was detected between the patients who had colorectal polyp, cancer and normal colonoscopy findings with regard to lactase gene polymorphism. No difference was determined between groups when compared with regard to C or T allele and also for the number and location of the polyps, genetic polymorphism.

Conclusion: The presence of a negative relationship between lactase deficiency and milk consumption is inevitable. Therefore, a relationship should be expected between lactase deficiency and colorectal cancer; however, such a relationship could not be determined in our study.

Disclosure of Interest: None declared

P1020 HIGH CARCINOEMBRYONIC ANTIGEN LEVEL MAY BE A DIAGNOSTIC MARKER FOR COLORECTAL ADENOMA IN KOREAN YOUNG MEN

H. S. Lee¹, I. C. Yoon¹, J. H. Cho¹, S. H. Lee¹, G. H. Lee¹

¹Department of Internal Medicine, Seonam University College of Medicine, Myongji Hospital, GOYANG-SI, Republic of Korea

Contact E-mail Address: epoch0123@naver.com

Introduction: Colon cancer is the 3^rd most commonly diagnosed cancer in South Korea. Colorectal cancer screening is recommended for average-risk persons beginning at age 50 in South Korea. However, prevalence of adenoma in subjects aged 40-49 years men was higher than we expected.

Aims & Methods: The aim of this study to determine the prevalence and risk factors of colorectal adenoma in persons aged 40-49 years men. 1902 asymptomatic subjects (1330 men, 69.9%, mean age of 47.9 ± 6.7) who underwent screening colonoscopy in a health examination center of Myongji hospital from 2010 to 2013 were enrolled in this study. We conducted case-control study to determine the risk factor for adenoma. The subjects were classified into two groups (adenoma vs controls and 40 – 49 years vs ≥50 years group).

Results: At least 1 colorectal neoplasm was identified in 385 patients (20.2%). 372 patients were found to have a non-advanced adenoma, 13 individuals had an invasive adenoma and no patient had a cancer. Male, old age, smoking, metabolic syndrome and elevated carcinoembryonic antigen (CEA) level were significantly associated with colorectal adenoma in univariate analysis. According to multiple logistic regression, adenoma was significantly associated with male and tended to be associated with high CEA level (p value =0.059). To validate the diagnostic values of CEA for adenoma, AUROC was calculated. Area under the curve of CEA for colorectal adenoma in non-smoking men (n=585) under 50 years was 0.600 (0.543∼0.656). Area under the curve of CEA for colorectal adenoma in smoking men (n=376) under 50 years was 0.615 (0.540∼0.690).

Conclusion: Male sex, metabolic syndrome, smoking and high CEA level seem to be associated with colorectal adenoma. High CEA level may be a diagnostic marker for any colorectal adenoma for 40 – 49 years Korean men. Further studies based on a large sample size will be needed to confirm the exact role of CEA for diagnostic marker of colorectal adenoma in Korean young men.

Disclosure of Interest: None declared

P1021 COMPARATIVE STUDY OF CLINICAL MANIFESTATIONS ACCORDING TO THE RESULTS OF INTERFERON-Γ ASSAY IN PATIENTS WITH INTESTINAL TUBERCULOSIS

H. J. Jung¹, Y. S. Kim², J. Y. Seo³, H. Jung⁴, J. P. Im³, J. W. Kim³, S. N. Hong⁴, Y.-H. Kim⁴, K. L. Lee³

¹Internal Medicine, International St. Mary’s Hospital, Incheon, ²Inje University College of Medicine, ³Seoul National University College of Medicine, ⁴Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

Contact E-mail Address: chamjin126@naver.com

Introduction: Intestinal tuberculosis (ITB) is still prevalent in Korea. Recently, the incidence of Crohn’s disease (CD) is also increasing, therefore, differential diagnosis of CD from ITB is challenging. An INF-gamma assay (QuantiFERON-TB gold test, QFT) is regarded as a good supplementary tool for the diagnosis of ITB. However, the clinical implication of the positive results of QFT in ITB is uncertain. We investigated the clinical features of patients of ITB according to the results of QFT.

Aims & Methods: We enrolled the ITB patients who were tested for QFT in the initial diagnosis from April 2007 to July 2013. We retrospectively analyzed clinical features of ITB patients based on the results of QFT.

Results: A total of 109 patients with ITB were enrolled from 3 institutes and 82 patients (75.2%) showed positive results of QFT, whereas 27 patients (24.8%) showed negative results. In QFT-positive group, the mean age at the time of diagnosis as ITB is 44.1 ± 12 years, which is significantly higher than QFT-negative group (37.0 ± 14.8 years, p=0.0096). C-reactive protein level at the time of diagnosis as ITB is significantly lower in QFT-positive group (1.3 ± 2.3 mg/dL) than QFT-negative group (6.4 ± 9.9 mg/dL, P < 0.000). However, no differences were found between groups regarding the presence of granuloma in colonic tissues (P=0.095) or accompanying of extra-intestinal TB (P=0.592).

Conclusion: QFT-positive results were gained in three-fourths patients with ITB and we confirmed that QFT is a good supplementary tool for the diagnosis of ITB. In QFT-positive group, the mean age is higher and has lower level of CRP than QFT-negative group. These results suggested the possibility that prior exposure to TB may cause mild inflammation in patients with ITB.

Disclosure of Interest: None declared

P1022 ASSOCIATION OF VISCERAL OBESITY WITH COLORECTAL ADENOMATOUS POLYPS AND COLORECTAL CANCER: A PRELIMINARY REPORT

I. S. Jung¹, C. M. Shin¹, S. J. Park¹, H. Yoon¹, Y. S. Park¹, N. Kim¹, D. H. Lee¹

¹Internal Medicine, Seoul National University Bundang Hospital, Seoungnam-si, Republic of Korea

Contact E-mail Address: scm6md@gmail.com

Introduction: Obesity is a well-established risk factor for colorectal adenoma, but its association with colorectal cancer (CRC) is not clear.

Aims & Methods: The aim of this study was to examine whether visceral adipose tissue (VAT) serves as a risk factor for CRC as well as colorectal adenomas. A retrospective case-control study was conducted with 45 patients with CRC (2 rectal and 43 colon cancers), 50 patients with colorectal adenoma and 50 normal controls. All subjects underwent various laboratory tests, computed tomography (CT) scan available for abdominal fat measurement, and colonoscopy. All patients with CRC also had available abdominal CT scan 1-2 years before the diagnosis. VAT was defined as an intraabdominal adipose tissue area measured by CT scan. Adipose tissue areas were measured at the level of the umbilicus from CT scan.

Results: Body mass index, fasting blood glucose (FBS) and VAT areas were significantly increased in adenoma and CRC groups compared to controls (all P < 0.01). The mean ± standard deviation of VAT area was 92.4 ± 4.8 cm² in normal controls, 120.9 ± 5.2 cm² in adenoma group and 123.2 ± 5.9 cm² in CRC group (P = 0.007 by ANOVA). On the other hand, subcutaneous adipose tissue areas were not different between the 3 groups (P > 0.05). Serum total cholesterol levels were significantly lower in CRC group than control or adenoma groups (P < 0.001). Although there was no significant difference in VAT areas between adenoma and CRC groups, VAT areas in CRC patients from CT scan taken 1-2 years before the diagnosis of CRC were significantly higher than those in adenoma group (P = 0.045).

Conclusion: Our study showed that both visceral obesity and insulin resistance were significant risk factors for CRC in the Korean population. However, the effect of visceral fat might be limited to the early stage of adenoma-carcinoma sequence in colorectal carcinogenesis. Further studies are warranted in the future.

Disclosure of Interest: None declared

P1023 CUMULATIVE INCIDENCE OF ADVANCED NEOPLASIA AFTER RESECTION OF HIGH AND INTERMEDIATE RISK ADENOMAS IN COLORECTAL CANCER POPULATION SCREENING PROGRAMS: RETROSPECTIVE COHORT STUDY

J. Cubiella¹, F. Carballo², I. Portillo³, J. Cruzado-Quevedo², D. Salas⁴, G. Binefa⁵, C. Hernandez⁶, M. Andreu⁷, A. Terán⁸, E. Arana-Arri³, F. Pérez-Riquelme⁹, M. J. Valverde⁴, N. Mila⁵, L. Bujanda¹⁰, V. Hernández¹¹, J. D. Morillas¹², F. Sopeña¹³, A. Castells¹⁴, R. Jover¹⁵

¹Gastroenterology, Complexo Hospitalario Universitario De Ourense, Ourense, ²Unidad de Gestión Clínica, IMIB Arrixaca. Hospital Clniico Universitario Virgen de la Arrixaca, Murcia, ³BioCruces, Hospital Universitario de Cruces, Bilbao, ⁴Programa Poblacional de Cribado de Cáncer Colorrectal, Dirección General de Salud Pública, Valencia, ⁵Programa de Prevención y Control del Cáncer, Instituto Catalán de Oncología-IDIBELL, L’Hospitalet de Llobregat, ⁶Servicio de Epidemiología y Evaluación, ⁷Servicio de Gastroenterología, Parc de Salut Mar, IMIM, Barcelona, ⁸Servicio de Aparato Digestivo, Hospital Universitario Marqués de Valdecilla, Santander, ⁹Programa de Cribado de Cáncer Colorrectal de la Región de Murcia, Instituto Murciano de Investigación Biosanitaria, Murcia, ¹⁰Servicio de Gastroenterología, Hospital Donostia/Instituto Biodonostia. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd). Universidad del País Vasco (UPV/EHU), San Sebastian, ¹¹Servicio de Gastroenterologia, Complexo Hospitlario Universitario de Vigo, Vigo, ¹²Servicio de Gastroenterologia, Hospital Clinico Universitario San Carlos, Madrid, ¹³Servicio de Gastroenterologia, Hospital Clínico Universitario de Zaragoza, CIBERehd, Zaragoza, ¹⁴Servicio de Gastroenterologia, Hospital Clínic, IDIBAPS, CIBERehd, Universitat de Barcelona, Barcelona, ¹⁵Unidad de Gastroenterología, Hospital General Universitario de Alicante, Alicante, Spain

Contact E-mail Address: joaquin.cubiella.fernandez@sergas.es

Introduction: European guidelines for quality in colorectal cancer (CRC) screening recommends different surveillance intervals in patients after adenoma resection. However, these recommendations have not been validated.

Aims & Methods

Aims: To assess whether the cumulative incidence of advanced neoplasia (AN) (advanced adenoma or CRC) and CRC in patients undergoing endoscopic surveillance differs between high-risk (≥5 adenomas or ≥ 20mm) and intermediate groups (2-4 adenomas or 10 to 19 mm or villous histology or high-grade dysplasia) of the European guidelines for quality in the CRC screening.

Methods: Retrospective cohort study of national ambit. We included subjects with high or intermediate risk adenomas detected in CRC population screening programs and in COLONPREV study from its inception until June 2011. The main dependent variable was the cumulative incidence of AN. We compared follow-up time with the Student’s t test. We analyzed the differences in endoscopic surveillance and the cumulative incidence of AN and CRC between both groups with the Mantel-Haenszel test. We performed a proportional hazards regression to control for confounding variables (sex, age, quality of baseline colonoscopy program and screening test). Differences between groups were expressed as risk ratio (RR) or hazard ratio (HR) and its confidence interval at 95% (95% CI).

Results: We included 5401 subjects, 3379 people with intermediate-risk adenomas and 2022 with high-risk adenomas (men = 70.1%, mean age = 60.9 ± 5.7 years, baseline number of colonoscopies = 1.2 ± 0.5, cecal intubation = 99.2%, adequate cleansing = 99.3%). A surveillance endoscopy was performed in 64.3% of subjects (high 68.2%, intermediate 62%; RR 1.3, 95% CI 1.2-1.5) at a mean interval of 2.8 ± 1 years (high = 2.7 ± 1.1, intermediate = 3 ± 0.9; p <0.001). In subjects with endoscopic surveillance, the cumulative incidence of AN in high and intermediate risk cohorts was 15.8% (58.6 cases per 1000 person-years) and 12.4% (41.9 cases per 1,000 people-year) with a RR = 1.3 (95% CI 1.1-1.6); and CRC cumulative incidence was 0.5% and 0.6% respectively (1.9 cases per 1000 person-years) with a RR = 0.9 (95% CI 0.3 to 2.2). In the proportional hazards analysis, the cumulative incidence of AN was higher in the high-risk cohort (HR 1.6, 95% CI 1.3-1.9). However, we found no differences in the cumulative incidence of CRC (HR 1.1, 95% CI 0.4 to 2.9).

Conclusion: In subjects performing endoscopic surveillance, the AN cumulative incidence is higher in the European guideline high risk group. However, we detected no differences in the CRC cumulative incidence between both cohorts.

Disclosure of Interest: None declared

P1024 DIAGNOSTIC RISK FACTORS FOR COLORECTAL CANCER IN PATIENTS WITH SERRATED POLYPOSIS SYNDROME

J. E. G. Ijspeert¹, S. A. Q. Rana², N. S. S. Atkinson³, Y. J. van Herwaarden⁴, T. M. Bisseling⁴, B. A. J. Bastiaansen¹, J. E. East³, A. Latchford², E. Dekker¹, on behalf of Dutch Workgroup Serrated Polyps, & polyposis (. WASP)

¹Academic Medical Centre, Amsterdam, Netherlands, ²St Mark’s Hospital, London, ³Translational Gastroenterology Unit, Oxford, United Kingdom, ⁴Radboud University Medical Center, Nijmegen, Netherlands

Introduction: Serrated polyposis syndrome (SPS) is characterized by multiple serrated polyps (SP) throughout the colon and accompanied by an increased life-time risk of colorectal cancer (CRC). SPS is diagnosed based on clinical criteria, which includes a very heterogeneous group of patients with a wide variation in CRC risk.

Aims & Methods: We aimed to assess CRC risk factors in a large cohort of patients with SPS and to evaluate the risk of CRC during surveillance. Patients were retrospectively enrolled from 7 centers in the Netherlands and 2 in the UK. Data were retrieved from medical charts, pathology and endoscopy reports. Criteria from the World Health Organization of 2010 were used to diagnose SPS (WHO1: ≥5 SP proximal to rectosigmoid with ≥2 of ≥10mm; WHO2: ≥1 SP proximal to rectosigmoid and a first degree relative with SPS; WHO 3: ≥20 SP of any size, but distributed throughout the colon). Patients that only fulfilled WHO criterion 2, with inflammatory bowel disease and/or a known hereditary CRC syndrome were excluded from analysis. Multivariate logistic regression was used to calculate adjusted risk factors for CRC. Incidence rate was calculated to evaluate the risk of CRC during surveillance after the resection of all lesions >5mm.

Results: In total 435 patients with SPS were included for analysis. The mean age at diagnosis was 58 years (SD 14), 49% were male and 57% of patients had a history of smoking. Of all patients, 27% fulfilled WHO criterion 1, 41% WHO criterion 3 and 32% WHO criteria 1&3. In total 128 (29%) patients were diagnosed with CRC. Patients with ≥1 SP with dysplasia (OR 2.05; 95%CI 1.26-3.31), ≥1 advanced adenoma (OR 2.31; CI 1.46-3.66) and patients that fulfilled WHO criteria 1&3 (OR 1.70; CI 1.10-2.57) were at increased risk of developing CRC, adjusted for age at SPS diagnosis (Table 1; only significant results shown). SPS patients with a history of smoking had a decreased risk of developing CRC (OR 0.35; CI 0.22-0.55). A total of 261 patients underwent surveillance after clearing of all lesions >5mm with a median follow up of 3.2 years (IQR 1.6-5.7) and a median interval between colonoscopies of 1.2 years (IQR 1.0-1.6). In total 3 patients were diagnosed with CRC during surveillance (2.90 events/1000 person years (95%CI 0.74-7.89).

Risk factors for CRC
	Univariate OR(95% CI)	p-value	Multivariable OR(95% CI)	p-value
Age at diagnosis SPS (per year)	1.04 (1.02-1.06)	<0.001	1.03 (1.01-1.05)	<0.001
History of smoking	0.48 (0.30-0.78)	<0.01	0.35 (0.22-0.55)	<0.001
≥1 SP containing dysplasia	2.31 (1.47-3.65)	<0.001	2.05 (1.26-3.31)	<0.01
≥1 advanced adenoma	2.49 (1.62-3.85)	<0.001	2.31 (1.46-3.66)	<0.001
Fulfilling WHO criteria 1&3	1.65 (1.07-2.54)	0.02	1.70 (1.10-2.57	0.02

Conclusion: SPS patients with advanced adenomas, SPs containing dysplasia and/or a combined WHO 1&3 phenotype are at an increased risk of developing CRC. Patients with a history of smoking show a markedly lower risk of developing CRC, possibly due to the fact that the pathogenesis of disease is different in these patients. The risk of developing CRC during surveillance and after clearing of all relevant lesions is lower than earlier assessed in literature, which may reflect a more mature multi-centre cohort with less selection bias.

Disclosure of Interest: None declared

P1025 THE APC I1307K ALLELE CONVEYS DIFFERENT RISKS FOR CANCER IN MEN AND WOMEN

N. Arber¹, S. Shapira¹, A. Leshno¹, S. Kraus¹, E. Liberman¹, M. Sror¹, A. Harlap Gat¹, L. Galzan¹, M. Moshkowitz¹, M. Serhan¹

¹Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

Contact E-mail Address: shiranshapira@gmail.com

Introduction: Background: The prevalence of the APC I1307K missense mutation is∼6% in Ashkenazi Jews (AJ) and is associated with an increased risk of colorectal (CRC) neoplasia.

Aims & Methods

Aim: To examine the association of this variant with non-CRC in a large cohort.

M&M: 13,017 consecutive healthy subjects, undergoing annual screening at Integrated Cancer Prevention Center in the past decade. This population was enriched with 1,607 cancer patients recruited from Oncology, Surgery, Gastroenterology, Urology and Hematology services. Demographics, medical history, and pathological data were recorded. Mortality data was obtained from Israel’s Ministry of Health registry. The APC I1307K analyses were performed using real-time PCR on DNA extracted from peripheral mononuclear cells. The detection rates of I1307K were compared using multiple variable logistic regression adjusted for age and sex. P-values for significance were adjusted to multiple testing by FDR methods.

Results: The I1307K was detected in 803/14,624 (5.5%) individuals (8.9% and 2.4% among Ashkenazi and Sephardic Jews). I1307K carriers showed a significantly increased risk for any type of cancer with an adjusted age and sex odds ratio (OR) of 2.53 (95% CI 2.11-3.04, P < 0.0001). In men increased risk for brain (OR 12.7), lung (7.3), urinary system (4.3), pancreas (3.7), BCC (3.2), and melanoma (3) was found. Female carriers showed a greater risk only for breast (2.8) and skin (4.8) cancers. A significantly increased CRC risk was found in men similar to previous studies: adenomatous polyps OR=1.67 (95% CI 1.23-2.25, P=0.001); CRC OR=1.90 (95% CI 1.35-2.69, P < 0.0001). In women increased risk only for adenomatous polyps OR=1.69 (95% CI 1.24-2.29 P < 0.001), but not for CRC. Carriers with one cancer were at significantly increased risk for developing at least one more cancer (OR 1.80 95% CI 1.14-2.8 P = 0.011). The increased risk for >2 cancers was significant only in women.

Overall survival between carriers and non-carriers using revealed that female carriers died at a significantly older age than non-carriers (average age of death 78.8 years, SE 2.2 vs. 70.4, SE 0.67 p=0.003). A Cox proportional hazard regression yielded a near significant HR of 0.69 (95% CI 0.47-1.01 p=0.055). iCarrier female cancer patients also had higher survival rate (HR 0.58, 95% CI 0.36-0.93 p = 0.022).

Conclusion: 1. The I1307K allele of the APC gene is a reliable marker for overall cancer risk (OR – 2.53) in particular in men. 2. This risk was higher than the prior described association with CR neoplasia. 3. In women the I1307K allele is only associated with an increased risk for breast and skin cancers and no increase in risk for CRC. 4. Carriage of this allele is associated with an unexplained significant 8 year increase in longevity in women.

Disclosure of Interest: None declared

P1026 MISMATCH REPAIR DEFICIENCY IN RADIOTHERAPY- AND CHEMOTHERAPY-ASSOCIATED COLORECTAL CANCER

L. S. Rigter¹, P. Snaebjornsson², E. H. Rosenberg², A. Broeks³, B. M. Aleman⁴, J. ten Hoeve⁵, G. A. Meijer², H. te Riele⁶, F. E. van Leeuwen⁷, M. E. van Leerdam¹

¹Gastroenterology, ²Pathology, ³Molecular Pathology, ⁴Radiation Oncology, ⁵Computational Cancer Biology, ⁶Biological Stress Response, ⁷Epidemiology, the Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, Netherlands

Contact E-mail Address: m.v.leerdam@nki.nl

Introduction: Hodgkin lymphoma (HL) survivors who were treated with infradiaphragmatic radiotherapy and/or high dose procarbazine have an approximately 5-fold increased risk to develop colorectal cancer (CRC) compared with the age-matched general population. The mechanism behind the transformation of normal colonic mucosa into CRC after exposure to radiotherapy or chemotherapy remains unknown. This study aims to provide insight into the development of treatment-induced CRC by evaluating the histopathological and molecular characteristics of treatment-induced CRC.

Aims & Methods: Formalin-fixed paraffin-embedded (FFPE) material from CRCs diagnosed in HL survivors was requested through the Nationwide Pathology Database (PALGA). Histopathological revision and immunohistochemical staining for mismatch repair (MMR) proteins were performed. Microsatellite stability status (pentaplex PCR) and CpG island methylator phenotype (CIMP, multiplex ligation-dependent probe amplification) status were assessed in all CRCs. Microsatellite instable (MSI) CRCs were additionally evaluated for promoter methylation of MMR genes.

Results: FFPE material of 51/64 (80%) cases was obtained, including 3 cases with 2 synchronous CRCs. The median age at CRC diagnosis was 57 years (range 30-79), 65% were male and the median latency between HL and CRC was 22 years (range 7-39). 13/54 (24%) CRCs were MSI and loss of staining was displayed for MLH1 and PMS2 (5/13) or MSH2 and MSH6 (7/13). One MSI tumor showed normal levels of all four MMR proteins. MLH1 promoter methylation was found in 3 MSI CRCs that showed loss of MLH1 and PMS2 protein staining. One MSS tumor showed loss of PMS2 staining; all the other MSS tumors stained positive for the four MMR proteins. 21/53 CRCs were CIMP (Ogino 5/8 gene positivity). The incidences of MSI and CIMP did not vary between different treatment groups (RT alone, procarbazine alone or RT + procarbazine).

Conclusion: In this study we demonstrated a high frequency of MSI among radiotherapy- and chemotherapy-associated CRCs, which surprisingly cannot be explained by promoter hypermethylation. Normal tissue and tumor DNA sequencing of MLH1, PMS2, MSH2 and MSH6 is in progress.

Disclosure of Interest: None declared

P1027 ALTERED EXPRESSION OF ACETYLCHOLINE RELATED PROTEINS IN NORMAL COLONIC MUCOSA FROM PATIENTS WITH COLORECTAL NEOPLASIA

M. M. B. Damm¹², T. S. R. Jensen¹, B. Mahmood¹², M. Lundh³, S. Knuhtsen¹, N. Bindslev², M. B. Hansen¹⁴

¹Digestive Disease Center K, Bispebjerg Hospital, ²Biomedical Sciences, ³The Novo Nordisk Foundation Center for Basic Metabolic Research, Integrative Physiology, University of Copenhagen, Copenhagen, Denmark, ⁴R&D, AztraZeneca, Mölndal, Sweden

Contact E-mail Address: morten.da2m@gmail.com

Introduction: Studies suggest that acetylcholine (ACh) plays a role in development of colorectal neoplasia (CRN). Local level of several transporters and enzymes involved in epithelial synthesis of ACh¹, muscarinic M3-receptor² and ACh esterase^1,3 appear dysregulated and involved in neoplastic cell-proliferation.

Aims & Methods: The aim of this study was to investigate the expression of genes coding for proteins related to epithelial synthesis and metabolism of ACh in colonic mucosa from patients with and without CRN. Furthermore, functional role of ACh was investigated. Endoscopic biopsies (N=25) from patients with CRN (CRN-pts) and controls were acquired from macroscopically normal mucosa in the sigmoid colon. qPCR was performed for the following 17 ACh-related genes: Choline transporter-like protein (CTL) 1-5, organic cation transporter 1-3, high-affinity choline transporter-1, vesicular ACh transporter, choline acetyltransferase, carnitine acetyltransferase, muscarinic receptor M1-3, ACh esterase and butyrylcholine esterase. All tests were run in triplicates and expression levels normalized with β-actin expression. Biopsies were mounted in micro-Ussing chambers and exposed to amiloride (20 µM) and subsequently increasing doses of ACh (0.125–2048 µM). Transepithelial electrogenic transport was measured by short circuit current (SCC). Data are reported as mean ± SEM. Statistical significance was tested using Student's unpaired t-test and Mann-Whitney U-test for equal and unequal variances of the groups, respectively. Unequal qPCR-data were first log-transformed. For categorical data Chi-square was used.

Results: qPCR: CTL1 and CTL4 were significantly increased in CRN-pts compared to controls. Relative expression level for CTL1 was 0.95 ± 0.06 in CRN-pts vs 0.61 ± 0.06 in controls (p = 0.002). Relative expression level for CTL4 was 0.57 ± 0.04 in CRN-pts vs 0.42 ± 0.06 in controls (p = 0.04). Ussing chamber: ACh induced rapid biphasic change in SCC. First part (decrease in SCC) was observed in 36 % of CRN-pts vs 78 % of controls (p=0.049). For the second part of SCC response (increase), double Michaelis-Menten analysis provided the best fit indicating activation of two receptors. For both parts of the biphasic response, the EC₅₀ and maximal responses showed no significant difference between CRN-pts and controls.

Conclusion: Data demonstrate increased expression of choline transporter CTL1 and ACh transporter CTL4 in mucosa from CRN-pts, indicating increased absorption/excretion of choline/ACh. Further, functional data demonstrate altered response to ACh in CRN-pts as measured by electrogenic transepithelial transport.

Disclosure of Interest: None declared

P1028 PERITONEAL DISSEMINATION IS MORE COMMON IN BRAF MUTATION THAN KRAS MUTATION OR KRAS/BRAF WILD TYPE IN COLORECTAL CANCER

N. Yujiro¹, M. Amaki¹, S. Natsume¹, T. Iijima¹, R. Wakaume¹, K. Takahashi¹, H. Matsumoto¹, D. Nakano¹, M. Miyaki¹, T. Yamaguchi¹

¹Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, TOKYO, Japan

Contact E-mail Address: nakayama.fd3s@gmail.com

Introduction: Molecular alterations are well studied in colorectal cancer, however there is still need for an improved understanding of their clinicopathological features. This study aims to characterize colorectal cancer with regard to KRAS and BRAF mutations in connection with tumor distant metastasis and prognosis in patients with colorectal cancer.

Aims & Methods: We consecutively selected 96 stage IV colorectal cancer patients who underwent surgical resection at the Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital from January 2008 to December 2011 after obtaining their informed consent. All samples were analyzed to identify any BRAF (V600E) and KRAS (codons 12 and 13) mutations by direct sequencing. Patients with inflammatory bowel disease, a known history of familial adenomatous polyposis, Lynch syndrome or microsatellite instable were excluded.

Results: Of the 96 colorectal cancer patients, 25 (26.0%) were KRAS mutation, 7 (7.3%) were BRAF mutation and 64 (66.6%) were KRAS/BRAF wild type. In total, 73 (76.0%) were hematogenous metastasis, 22 (22.9%) were lymphogenous metastasis and 27 (28.1%) were peritoneal dissemination. In KRAS mutation patients, 8 (20%) were containing dissemination. In BRAF mutation patients, 5 (71%) were peritoneal dissemination and 14 (21.9%) in KRAS/BRAF wild type. Dissemination were significantly more common in BRAF gene mutation than in KRAS/BRAF wild type (Fisher’s exact test, p= 0.01). Median survival time were 692 days in KRAS gene mutation, 470 in BRAF gene mutation and 1143 in wild type (logrank test, p < 0.01).

Conclusion: Peritoneal dissemination is more common in BRAF mutation than KRAS mutation or wild type in colorectal cancer.

Disclosure of Interest: None declared

P1029 IDENTIFICATION OF NORE1A AS A NEGATIVE FEEDBACK REGULATOR OF TNFA-NF-κB SIGNALING, WHICH DIRECTS APOPTOTIC SWITCH OF TNFA FUNCTION IN COLORECTAL TUMOR CELLS

N.-H. Kim¹, K.-P. Ko², S.-G. Chi²

¹Department of Internal Medicine, Ilsan Paik Hospital, Inje University, Goyang, ²Department of Life Science, Korea University, Seoul, Republic of Korea

Contact E-mail Address: n-hkim@paik.ac.kr

Introduction: NORE1A (RASSF5), a member of the Ras-association domain family (RASSF) of proteins, plays an important role in various cellular processes, including cell proliferation and apoptosis. NORE1A expression is commonly silenced or down-regulated in many human malignancies, including colorectal cancer. However, the mechanisms underlying its tumor suppressive functions have not been entirely defined.

Aims & Methods: To explore whether NORE1A inactivation is associated with colorectal tumor cell resistance to TNFα-induced apoptosis, we investigated TNFα effect on NORE1A expression using semi-quantitative RT-PCR and immunoblotting assay. NORE1A regulation of TNFα-NF-κB signaling and its cellular effects were defined by luciferase reporter and flow cytometric analyses and cell proliferation and apoptosis assays.

Results: NORE1A transcription was activated by TNFα and its induction strongly increased apoptotic response of colorectal tumor cells to TNFα. TNFα activation of NORE1A was disrupted when the RIPK1-IκBα-NF-κB signaling was blocked while it was further enhanced by p65/RelA transfection, indicating that NORE1A is a novel transcriptional target of TNFα-NF-κB signaling, which stimulates apoptosis-promoting function of TNFα. We also found that TNFα-induced NORE1A causes a rapid degradation of TNFα receptor type I (TNFRI) protein and subsequently suppresses NF-κB signaling, indicating the presence of a negative feedback regulatory loop between TNFα and NORE1A. Intriguingly, NORE1A degradation of TNFR1 was found to selectively impede TNFα-mediated RIPK1-IκBα-NF-κB signaling, thus blocking NF-κB-mediated cell growth and survival, whereas it facilitates TNFα-induced caspase activation and apoptosis. We finally observed that restoration of NORE1A expression in nonexpressing tumor cells strongly enhances apoptotic sensitivity of tumor cells to TNFα, suggesting that loss of its expression in tumorigenic process might be a key event that debilitates TNFα’s proapoptotc effect.

Conclusion: Our data demonstrate first that NORE1A is a negative feedback regulator of TNFα, which directs apoptotic switch of TNFα function by selectively impeding TNFα-NF-κB signaling. These results strongly suggest that NORE1A inactivation might be a critical event that drives the oncogenic conversion of TNFα function in colorectal tumorigenesis.

Disclosure of Interest: None declared

P1030 THE ASSOCIATION OF GENETIC VARIATION WITHIN THE WNT SIGNALLING PATHWAY WITH COLORECTAL CANCER: A META-ANALYSIS

S. S. Malik¹, K. J. Monahan¹, M. McPhail¹

¹Family History of Bowel Cancer Clinic, West Middlesex University Hospital and Imperial College, London, London, United Kingdom

Contact E-mail Address: salim.malik10@imperial.ac.uk

Introduction: 35% of colorectal cancer (CRC) risk is attributable to heritable factors, of which a large proportion remains unexplained. Genome wide association studies have conclusively identified several risk variants in the TGF-beta pathway. Both TGF-beta and Wnt pathways are key regulators of colonic crypt homeostasis and colorectal carcinogenesis. The Wnt pathway is deregulated in 93% of CRCs, however the role of Wnt pathway genetic variation in CRC risk is uncertain.

Aims & Methods: The aim is to perform a systematic review and meta-analysis to assess the association of polymorphisms within the Wnt signalling pathway and the risk of CRC.

A systematic literature review of the Pubmed and HuGENet databases was conducted. Studies were included/excluded based on pre-specified criteria. In order to assess the risk attributed to each identified variant, the ‘per allele’ model was utilised to calculate pooled odds ratios. Heterogeneity was investigated by subgroup analyses for ethnicity, gender and tumour location. Publication bias was investigated using funnel plots and Egger’s test. Statistical analysis was conducted using the R program (version 3.1.0).

Results: Forty-three polymorphisms across 18 different genes in the Wnt pathway were identified. Meta-analyses were conducted for 12 of these polymorphisms including between 831 to 31,427 cases per polymorphism. 6 polymorphisms were significantly associated with the risk of CRC. Rs1801155 within APC (OR= 1.79; 95% CI 1.27-2.52) and rs10505477 at the 8q24.21 locus (OR= 1.15; 95% CI 1.12-1.19) were associated with an increased risk of CRC. rs16260 (OR=0.94; 95% CI 0.89-0.99) and rs9929218 (OR=0.93; 95% CI 0.90-0.95) within CDH1; rs6983267 (OR=0.85; 95% CI 0.83-0.87) within MYC and rs7014346 (OR=0.87; 95% CI 0.81-0.94) at the 8q24.21 locus, were associated with a decreased risk of CRC. Subgroup analysis revealed gender, ethnicity and tumour location were not sources of heterogeneity.

Conclusion: Six polymorphisms associated with CRC risk account for a significant proportion of familial risk, although are unlikely to account completely for aberrant activation of the Wnt pathway. These polymorphisms are located within APC, CDH1 and MYC genes and the 8q24.21 locus. Further research into their precise role in colorectal carcinogenesis is warranted. Meta-association studies of all SNPs in the Wnt pathway should be conducted to identify further risk variants. Rare variants, copy number variations and epigenetic alterations may contribute to the remaining heritability and Wnt pathway activation.

Disclosure of Interest: None declared

P1031 IMMUNESURVEILLANCE IN NON INFLAMMATORY COLORECTAL CARCINOGENESIS: EPITHELIAL CELLS IN ADENOMA ENHANCE THEIR ANTIGEN PRESENTATION CAPABILITY WITHOUT ELICITING A STRONG IMMUNE RESPONSE

M. Scarpa¹, S. Melania¹, I. Castagliuolo², S. Morgan³, A. Kotsafti¹, A. Porzionato², P. Brun², T. Morbin⁴, S. Realdon⁴, C. Ruffolo⁵, F. Ferrara⁶, C. Fornasier⁷, G. Pirozzolo⁷, M. Rugge⁸, I. Angriman⁹, C. Castoro¹⁰

¹Oncological Surgery Unit, Veneto Institute of Oncology (IOV-IRCCS), ²Dept of Molecular Medicine, University of Padova, Padova, Italy, ³Dept. of Histopathology, Sheffield Teaching Hospitals, Sheffield, United Kingdom, ⁴Endoscopy Unit, Veneto Institute of Oncology (IOV-IRCCS), Padova, ⁵General Surgery Unit (IV), Hospital Ca' Foncello, ⁶Gastroenterology Unit, Ca Foncello Hospital, ⁷General Surgery Unit (IV), Ca' Foncello Hospital, Treviso, ⁸Dept of Medicine, ⁹General Surgery Unit, University of Padova, ¹⁰Oncological Surgery Unit, Veneto Institute of Oncology, Padova, Italy

Contact E-mail Address: marcoscarpa73@yahoo.it

Introduction: In non inflammatory colorectal cancer, T cell populations were demonstrated to play a significant role in the patients prognosis although it is not clear the trigger of this immune response and its efficiency in the preneoplastic lesions. Costimulatory interactions are decisive in sensitization of T cells by antigen presenting cells and important for the elicitation of the immune responses. Our previous studies demostrated that immunesurveillance mechanisms mediated by CD80-CD28 signalling may lead to dysplasia regression in ulcerative colitis.

Aims & Methods: The aim of this multicentric study was to explore the effect of CD80-CD28 signaling in human non inflammatory carcinogenesis and in a murine model of colonic carcinogenesis.

We prospectively enrolled 105 subjects who underwent screening colonoscopy or colectomy: 45 of them had an adenoma, 45 had an adenocarcinoma and 15 were healthy subjects. Biopsies were taken from their healthy mucosa and colonic lesions. Flow cytometry for CD8 + CD28+ or CD8 + CD38+, CD4 + CD25+ and CD25 + FoxP3+ lymphocytes and for CD80+ or HLA ABC+ epithelial cells were performed.

The azoxymethane (AOM)-induced colon carcinogenesis mouse model was used to block in vivo CD80 signaling by administration of neutralizing antibodies against CD80 or isotype control. Mice were euthanized 4 and 6 months after the first AOM injection. Colons were removed and examined. Flow cytometry was performed. Non parametric statistics was used.

Results: A higher rate of epithelial cells expressing CD80 or HLA-ABC was observed in colorectal adenoma compared to healthy colonic mucosa (p=0.036 and p=0.022, respectively) and colorectal adenocarcinoma (p=0.19 and p=0.008, respectively). The rate of CD8 + CD28+ and CD8 + CD38+ lymphocytes resulted higher in colorectal adenocarcinoma than in colorectal adenoma (p=0.001 and p=0.005, respectively).

We observed a higher rate of CD80+, MHC-I+ and MHC-II+ epithelial cells (p=0.004, p=0.02 and p=0.002, respectively) and of activated lymphocytes (CD4 + CD25+, CD8 + CD28+ and CD8 + CD69+) (p=0.002, p=0.002 and p=0.015, respectively) in mice sacrificed at 4 months than in those sacrificed at 6 months. Administration of anti-CD80 significantly increased the frequency of HGD (p=0.02).

Conclusion: Epithelial cells of colorectal adenoma activate their capability of antigen presentation without eliciting a strong immune response. In the AOM mouse model, the antigen presenting activity and the immune response is more activated in a very early stage of the carcinogenesis. Our hypothesis is that some inhibitors (CTLA-4 or PD-1) can interfere with the immunesurveillance mechanisms in non inflammatory colorectal carcinogenesis.

Disclosure of Interest: None declared

P1032 ASYMPTOMATIC RADIOLOGICALLY DETECTED COLONIC PERFORATIONS IN THE ENGLISH NHS BOWEL CANCER SCREENING PROGRAMME (NHSBCSP)

E. Derbyshire¹, A. Hungin², C. Nickerson³, M. D. Rutter¹, on behalf of NHSBCSP Evaluation Group

¹North Tees & Hartlepool NHS Foundation Trust, Stockton-on-Tees, ²Durham University, Durham, ³NHS Cancer Screening Programmes, Sheffield, United Kingdom

Introduction: Colonoscopies in the English NHSBCSP are offered to 60-74 year olds with an abnormal Faecal Occult Blood Test. Colonoscopic perforation remains one of the most serious adverse events associated with colonoscopy. Patients typically present with symptoms as a result of peritoneal irritation, however, colonic perforation may be diagnosed radiologically in patients who are entirely asymptomatic.

Aims & Methods: The aims of this study were to identify cases of asymptomatic radiologically detected colonic perforation in the English NHSBCSP, describe similarities between them and explore why such perforations occur. We identified all reported cases of colonoscopic perforation from the start of the NHSBCSP in 2006 up to and including 13/03/2014 from the web-based database used by the NHSBCSP, the Bowel Cancer Screening System. The NHSBCSP definition of perforation is: air, luminal contents or instrumentation outside the gastrointestinal tract. Bowel Cancer Screening Centres were subsequently asked to complete an online questionnaire relating to the patient’s post perforation presentation, assessment management, and outcome.

Results: Of 147 perforations identified, complete data on 117 was received. Four asymptomatic radiologically detected colonic perforations were identified. Case 1 was a biopsied rectal cancer. Staging Magnetic Resonance Imaging (MRI) and staging Computed Tomography (CT) 12 and 14 days respectively following colonoscopy noted a sealed off perforation posterior to the rectum. Two cases were associated with a biopsied sigmoid cancer; one a perforation identified at staging CT 2 days following colonoscopy, the other on a same day completion CT virtual colonoscopy after the cancer was impassable endoscopically, showing gas to the right of the tumour. Case 4 was a biopsied cancer at the hepatic flexure with perforation diagnosed on staging CT 24 hours later. TNM classification was reported in 3 cancers: T3N0M0, T4N1MO and T4N2M0. Histology confirmed either well or moderately differentiated adenocarcinoma in 3 cancers. Two of these patients were recalled to hospital following CT findings, subsequently having surgery. The other 2 did not require immediate admission.

Conclusion: All asymptomatic radiologically detected perforations were associated with colorectal cancer seen on staging radiological investigation where the cancer had been cold biopsied. It is likely that only perforations associated with cancer will present asymptomatically as it is only they that have staging radiological investigation. The cancers were in the rectum, sigmoid colon and hepatic flexure. TNM classification was at least T3. Emergency surgery was not required in three of these patients. The underlying cause of this is sub group of perforations is perhaps more likely to be due to invasion of the cancer and not the biopsy, however, a larger case series is required to confirm these findings.

Disclosure of Interest: None declared

P1033 POSITIVE PREDICTIVE VALUE INCREASES WITH AGE IN A FECAL IMMUNOCHEMICAL TEST BASED COLORECTAL CANCER SCREENING PROGRAM

E. Wieten¹, E. J. Grobbee¹, B. E. Hansen¹, M. J. Bruno¹, E. J. Kuipers¹, I. Lansdorp-Vogelaar², M. C. W. Spaander¹

¹Gastroenterology & Hepatology, ²Public Health, Erasmus MC University Medical Centre, Rotterdam, Netherlands

Contact E-mail Address: e.wieten@erasmusmc.nl

Introduction: There is a good correlation between concentration of fecal hemoglobin (Hb) in fecal immunochemical tests (FITs) and age. Previous studies have shown that fecal Hb concentrations in stool and positivity rate (PR) increase with age. It is currently unknown whether that increase is mainly the result of a higher detection rate (DR) of advanced neoplasia (AN) or an increase in false positive rate (FPR). Quantitative FIT enable to choose the preferred fecal Hb concentration for colonoscopy referral. So far, cutoff values have been set to one fixed level for all ages. However, age partitioned reference values for fecal Hb concentration may be warranted if FPR increases relatively more with age than DR. The aim of this study was to assess the relation of FPR and DR with age and its influence on positive predictive value (PPV).

Aims & Methods: All average risk individuals, aged 55-75 years, who completed one sample FIT in a first round of a population-based colorectal cancer (CRC) screening pilot were included. A positivity cut-off level of 10 µg Hb/gram feces (>50 ng Hb/ml) was used. All screenees with a positive test were offered colonoscopy. We calculated age-specific PR, DR, FPR and PPV. Logistic regression analyses were performed to determine the independent association of PPV with multiple variables (sex, age, social economic status, fecal Hb concentration). Variables achieving a P value of less than 0.05 were included in a multivariate logistic regression analyses, as were variables included by the clinician’s rationale (gender).

Results: Of the 10.008 invitees, 5,986 persons (mean age 60.4 (±6.8) years; 49.7% males) participated and 503 (8.4%) persons had a positive test. Attendance rate, PR and DR were significantly higher in the older age categories (p < 0.001). Multivariate logistic regression analyses, with age as continues variable, showed PPV increased significantly with age and fecal Hb concentration when corrected for gender, Table 1. There were no significant differences in frequencies between the observed values and the predicted values of the model (Hosmer and Lemeshow Goodness-of-Fit Test; p=0.183).

Table 1.

Uni- and multivariate logistic regression analyses with the positive predictive value of having advanced neoplasia as dependent variable.

	Univariate		Multivariate
	Odds ratio (95% CI)	p-value	Odds ratio (95% CI)	p-value
Sex male	1.31 (0.90-1.90)	.154	1.17 (0.79-1.74)	.435
Age (per ten years)	1.55 (1.18-2.06)	.002	1.55 (1.16-2.09)	.004
Socio-economic status		.330
High	Reference
Middle	1.14 (0.70-1.87)
Low	1.36 (0.91-2.04)
Fecal Hb concentration (per 10 µg Hb/g feces)	1.07 (1.05-1.09)	<.001	1.07 (1.05-1.09)	<.001

Conclusion: PPV increases significantly with age and fecal Hb concentration in a FIT-based CRC screening program. This implies a relatively larger increase of DR compared to FPR with age. These results suggest age-partitioned reference values for fecal Hb concentration are not warranted.

Disclosure of Interest: None declared

P1034 SENSITIVITY OF PRETARGETED 68GA PET-CT TO DETECT COLORECTAL CARCINOMA LIVER METASTASIS IN A MOUSE MODEL: COMPARISON WITH 18FDG PET-CT

F. Foubert¹², M. Cherel²³, A. Faivre-Chauvet²³, S. Gouard²³, C. Maurel²³, Y. Touchefeu¹², E. Frampas²⁴

¹Institut des Maladies de l'Appareil Digestif, ²INSERM UMR 892, ³University of Nantes, ⁴Radiology department - CHU, Nantes, France

Contact E-mail Address: marietillie@hotmail.com

Introduction: The aim of our study was to compare the performances of a pretargeted PET (pPET) imaging with anti-CEA (carcinoembryonic antigen) and anti-HSG (histamine-succinyl-glycine) recombinant humanized bispecific monoclonal antibody (TF2) and ⁶⁸Ga-labeled HSG peptide (IMP288) to conventional ¹⁸FDG PET in an orthotopic murine model of colorectal cancer liver metastasis.

Aims & Methods: CEA expression of colorectal cancer cells (LS174T Luc) was assessed in vitro by flow cytometry and in vivo by CEA staining. Hepatic tumors were grafted by intraportal injection and tumor burden was confirmed using bioluminescence. One group was pretargeted with TF2 and received IMP288-⁶⁸Ga 24 hours later (n=8). One group received ¹⁸FDG (n=8). One group had both imaging modalities (n=7). PET acquisitions started 1 hour after radionuclide injection. Biodistributions of the ⁶⁸Ga labeled peptide and ¹⁸FDG in tumors and normal tissues were assessed one hour after imaging.

Results: LS174T Luc cells expressed CEA. Considering tissues uptakes, Tumor/Organ ratio with ⁶⁸Ga-PETp were statistically significantly higher compared to ¹⁸FDG PET (p < 0.05) with both imaging and biodistribution data. ⁶⁸Ga-PETp sensitivity for tumor detection was 67% versus 31% with ¹⁸FDG PET (p=0.049). For smaller tumors less than 200 mg, the sensitivity was 44% with ⁶⁸Ga-PETp versus 0% with ¹⁸FDG PET (p=0.031). A strong correlation was demonstrated between signals measured on PET images and biodistribution analyzes (r²=0.85).

Conclusion: ⁶⁸Ga-PETp was more sensitive than ¹⁸FDG-PET for the detection of colorectal liver metastasis in an orthotopic murine model. Improved Tumor/Organ ratio allows imaging and therapeutic considerations.

Disclosure of Interest: None declared

P1035 DIAGNOSTIC ACCURACY AND INTEROBSERVER CONSISTENCY FOR THE ENDOSCOPIC PREDICTION OF SESSILE SERRATED ADENOMAS/POLYPS

H.-J. Yang¹, J. I. Lee¹, I. D. Park ¹, S.-K. Park¹, Y. S. Jung¹, K. Y. Choi¹

¹Department of Internal Medicine and Colon Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

Contact E-mail Address: hyojoonyang@gmail.com

Introduction: It may be challenging to recognize sessile serrated adenomas/polyps (SSA/Ps) and to differentiate them from hyperplastic polyps (HPs) or tubular adenomas (TAs) during colonoscopy evaluation. Although several studies suggested endoscopic features of SSA/Ps, the external validity and interobserver consistency of those features are not well studied.

Aims & Methods: This study aimed to examine diagnostic accuracy and interobserver consistency of endoscopic features for the diagnosis of SSA/Ps using high-resolution white-light endoscopy.

Endoscopic images of 81 polyps (29 SSA/Ps, 19 HPs, and 23 TAs) from 43 patients undergoing screening colonoscopy between March 2005 and April 2014 at a single tertiary care center were retrospectively evaluated by 10 colonoscopists. Eight endoscopic features of SSA/Ps (indistinctive border, irregular shape, rim of debris, cloud-like surface, mucous cap, nodular surface, absence of vessels, and dark spots) were assessed for each polyp in three stages: learning set, consensus meeting, and validation set.

Results: In the validation set, the prevalence of the features was ranged from 21.7% of SSA/Ps for dark spots to 51.0% for indistinctive border. In the multivariable analysis, mucous cap (odds ratio [OR], 10.10; 95% confidence interval [CI], 6.44–16.00, p <0.001), cloud-like surface (OR, 3.05; 95% CI, 1.74–5.32, p <0.001), indistinctive border (OR, 2.38; 95% CI, 1.53–3.69, p <0.001), rim of debris (OR, 2.04; 95% CI, 1.43–3.55, p <0.001), and dark spots (OR, 1.76; 95% CI, 1.11–2.80, p = 0.016) were independent predictors of SSA/Ps compared to HPs and TAs. The number of the independent predictors showed excellent discrimination (area under the receiver-operating characteristic curve [AUROC], 0.80). When ≥1 of the predictors were observed, SSA/Ps could be diagnosed with a sensitivity of 85.2% and specificity of 63.9%. Nevertheless, the interobserver agreement on the independent predictive findings demonstrated only moderate to fair κ-values (range, 0.25–0.41) except for dark spots, which showed poor interobserver agreement (κ = 0.12).

Conclusion: Several features of SSA/Ps were found to provide reliable accuracy for the endoscopic prediction of SSA/Ps. However, the interobserver agreements of the features remain to be improved.

Disclosure of Interest: None declared

P1036 MODEL OF INVITATION TO ENSURE HIGH PARTICIPATION ON THE COLORECTAL CANCER SCREENING PROGRAMME OF THE BASQUE COUNTRY (SPAIN)

I. Idigoras Rubio¹, E. Arana-Arri², I. Portillo¹, I. Bilbao¹, J. L. Hurtado³, M. L. Jauregui⁴, L. Martinez², I. Gutierrez-Ibarlucea⁵

¹Department of Health Basque Country, Osakidetza, ²Biocruces, Huc, Bilbao, ³Department of Health Basque Country, Osakidetza, Vitoria Gasteiz, ⁴Department of Health Basque Country, Osakidetza, Zumarraga, ⁵Department of Health Basque Country, Dto De Salud, Vitoria Gasteiz, Spain

Introduction: : The aim of this study is to evaluate the evolution of Participation Rate (PR) and trends of the Colorectal Cancer Screening Programme carried out in the Basque Country. This Programme started in 2009, based on the detection of occult blood in faeces every two years and colonoscopy under sedation as a confirmed diagnosis. According to the European Guidelines (2010) recommendations, the key point to obtain an efficient program depends on the overall PR. Involving and Coordinating staff of different health care levels and developing innovative methods can increase PR.

Aims & Methods: a) Before the invitation, the Program Coordination Centre staff plans and organizes the elected Primary Care Center involved and agrees with hospitals the capacity to perform screening colonoscopies. b) A specific program software connected with other electronic medical data bases (medical records, hospital discharges, Cancer Registries and mortality), selects (50-69 year-old residents) and excludes (CRC diagnosed, colonoscopy in the last 5 years). c) Certified training is offered to all staff in the health centers. d) A personalized invitation letter, explaining the aims and methods of the programme was sent, including a free phone line, e-mail and web-site for further clarifications. Nevertheless, the person decides to participate or not. e) Afterwards, the kit, instruction leaflet with a personal code is delivered by post. f) Once the person decides to participate, the kit can be left in Health Care Centers without any previous appointment and guaranteed quality controls.

Results: : At the beginning of the program (2009) the overall PR was 58.1%, reaching 68.9% in first round in 2013. Once analyzed by sex PR for women increased from 61.3% to 71.3% and from 54.6% to 66.3% for men. All trends of PR were positive, 1.032 for overall PR (p < 0.001); 1.034 for women (p < 0.001) and 1.029 for men (p < 0.001). In the second round we have observed that the PR also increased, overall PR went from 67.0% to 70.7% (Trend=1.029, p < 0.001), in women from 71.4% to 73.1% (Trend=1.019, p < 0.001) and in men from 62.5% to 68.2% (Trend=1.043, p < 0.001). We have analyzed trends by sex/age ranges (younger/older than 60 years), and we observed that all trends were positive being higher in women and participants older than 60 years.

Conclusion: This work demonstrates that the strategy invitation in a screening programme markedly influences on PR. The choice of the kit, way of shipping/collection and other factors such as the involvement of primary care physicians could be crucial.

Disclosure of Interest: None declared

P1037 CLINICOPATHOLOGICAL FEATURES OF T1 COLORECTAL CARCINOMAS WITH “SKIP INVASION”

Y. Sato¹, S.-E. Kudo¹, K. Ichimasa¹, H. Miyachi¹, Y. Kimura¹, Y. Kouyama¹, K. Kato¹, S. Matsudaira¹, M. Oikawa¹, M. Misawa¹, Y. Mori¹, T. Kudo¹, T. Hisayuki¹, K. Kodama¹, T. Hayashi¹, K. Wakamura¹, A. Katagiri¹, T. Baba¹, E. Hidaka¹, H. Ishida¹

¹Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama city, Japan

Contact E-mail Address: ssteadfastness@yahoo.co.jp

Introduction: With recent advances in endoscopic treatment, many T1 colorectal carcinomas are now resected endoscopically with negative margins. However, there are some cases with “Skip Invasion”, which is defined as discontinuous foci of carcinoma cells in the deeper layer of the colon apart from the invasive front, and “Skip Invasion” cannot be diagnosed with current endoscopic procedures.

Aims & Methods: The aim of this study was to investigate the clinicopathological features of T1 colorectal carcinomas with “Skip Invasion”.

Of the 23725 colorectal neoplasms excluding advanced carcinomas which have been resected endoscopically or surgically at our institution from April 2001 to November 2014, 653 T1 carcinomas surgically resected were investigated. Then clinicopathological features of T1 carcinomas with and without “Skip Invasion” were compared. The factors for the analysis were patient age, sex, tumor size, location, morphology, degree of submucosal invasion, lymphovascular invasion, tumor budding, and histological type (por or muc component).

Results: There were 4 lesions (0.6%) with “Skip Invasion”. All lesions with “Skip Invasion” were observed in sigmoid colon (p = 0.02) and showed lymphovascular invasion (p = 0.13). There were no significant differences in the other factors. One of 4 lesions showed the presence of lymph node metastasis.

Conclusion: All lesions with “Skip Invasion” were in sigmoid colon and showed lymphovascular invasion. These lesions were rare, but they certainly exist and might cause poor prognosis. Further caution should be needed for lesions with lymphovascular invasion, especially in sigmoid colon.

Disclosure of Interest: None declared

P1038 FECAL OCCULT BLOOD TESTS SHOW LOWER CANCER DETECTION RATE IN THE PROXIMAL COLON: A META-ANALYSIS OF 47 DIAGNOSTIC STUDIES

K. K. Tsoi¹², S. C. Ng³, H. W. Hirai²³, J. Y. Chan¹, J. Y. Ching³, M. C. Wong¹, J. C. Wu³, F. K. Chan³, J. J. Sung³

¹School of Public Health and Primary Care, ²Big Data Decision Analytics Research Centre, ³Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong

Contact E-mail Address: kelvintsoi@cuhk.edu.hk

Introduction: Diagnostic accuracy of fecal occult blood tests (FOBTs) differ widely in studies of colorectal cancer screening. This meta-analysis aims to evaluate the diagnostic accuracy of FOBTs for the detection of colorectal cancer (CRC) in the proximal colon.

Aims & Methods: Studies assessing performance of FOBTs were searched from the OVID databases up to 28 February 2015. Studies were eligible if subjects received FOBTs to estimate the diagnosis of CRC which was confirmed by colonoscopy. Analyses were conducted separately for Guaiac-based and Immunochemical-based FOBT (gFOBT and iFOBT). Main outcomes included sensitivity and specificity of FOBTs. Bivariate random-effects model was applied to combine the results from individual studies. Subgroup analyses were performed to evaluate the test performances based on location of neoplasia and the brands of FOBTs.

Results: A total of 47 studies with 79,605 subjects (gFOBTs: 28 cohorts; iFOBTs: 42 cohorts) were identified from 18 geographic regions. In the gFOBT group, the combined sensitivity and specificity for CRC were 62.2% (95% CI=51.0% to 72.2%) and 93.4% (95% CI=91.0% to 95.2%) respectively. In iFOBT group, the combined sensitivity and specificity for CRC were 84.4% (95% CI=79.9% to 88.1%) and 92.3% (95% CI=89.7% to 94.3%). The diagnostic performance of gFOBT was significantly lower than that of iFOBT (AUC=91% vs 95%, p=0.014). Subgroup analysis showed that both FOBTs have higher sensitivity and comparable specificity for CRC detection in the distal colon compared with the proximal colon. (iFOBT sensitivity: 80% vs 72%; gFOBT sensitivity: 72% vs 64%). The diagnostic performances across different brands of FOBTs were comparable.

Conclusion: The diagnostic accuracy of FOBTs for CRC is good. iFOBTs showed better performance than gFOBT, and both FOBTs showed better CRC detection on the distal colon. Annual screening with iFOBT is recommended to reduce the chance of missing detection on proximal colon.

Disclosure of Interest: None declared

P1039 CLINICAL SIGNIFICANCE OF SUBCLASSIFICATION FOR COLORECTAL LATERALLY SPREADING TUMOR (LST) GRANULAR TYPE

K. Shigita¹, S. Tanaka¹, S. Oka¹, K. Sumimoto², D. Hirano², Y. Tamaru², Y. Ninomiya², N. Asayama², N. Hayashi¹, K. Chayama², K. Arihiro³, S. Nagata⁴

¹Department of Endoscopy, ²Department of Gastroenterology and Metabolism, ³Department of Pathology, Hiroshima University, ⁴Department of Endoscopy, Hiroshima City Asa Hospital, Hiroshima, Japan

Contact E-mail Address: k-shigita@hiroshima-u.ac.jp

Introduction: Colorectal laterally spreading tumor-granular type (LST-G) is divided into 2 subtypes according to its morphology: homogenous type and nodular mixed type. However, the present LST-G subtype classification has not been defined by concrete objective findings but the concept of morphology without definite criteria.

Aims & Methods: This study was aimed to clarify the clinical significance of concrete objective LST-G subclassification according to the diameter of their granules or nodules. A total of 636 consecutive cases with LST-G that was resected endoscopically or surgically in Hiroshima University Hospital and Hiroshima City Asa Hospital between January 2008 and December 2014 entered this study. LST-Gs were divided into three types as follows; Type1: a lesion with homogenous uniform granules (<5mm), Type 2: a lesion with granules and small nodules (5mm≤, <10 mm), Type 3: a lesion accompanied by large nodules (≥10 mm). We evaluated interobserver agreement for subclassification of LST-G and accuracy in each group. Also, we investigated case characteristics and clinicopathologic features (sex, age, tumor size, location, histology, and invasion depth) for each LST-G subtype in whole 636 lesions. In validation study, a total of 194 fine images in 97 cases with conventional endoscopy and chromoendoscopy with indigo carmine dye spraying were distributed in randomized order to medical students with no prior endoscopy experience (Student Group), less-experienced endoscopists (LEE Group) and high-experienced endoscopists (HEE Group).

Results: Interobserver agreements were >0.6 representing good agreement in all groups. Diagnostic accuracy in HEE Group was higher than students and LEE Group. Chromoendoscopy had higher accuracy rate than conventional endoscopy in LEE Group (74% vs 69%, p < 0.05) and HEE Group (84% vs 78%, p < 0.05). As for the misdiagnositc lesions, participants in all groups tended to misdiagnose Type 1 as Type 2, and Type 3 as Type 2. Meanwhile, in the lesion of Type 2, lesions were prone to misdiagnose as Type 3 in LEE Group and HEE Group but as Type 1 in Student Group. Type 2 and Type 3 lesions were significantly larger than Type 1 lesions (Type 1: 21 ± 10mm, Type 2: 39 ± 22mm, Type 3: 46 ± 20mm, p < 0.01). The incidence of carcinoma in Type 1 was much lower than that in Type 2 and Type 3 (3% [4/154], 62% [141/226], 63% [162/256], respectively; p < 0.01). The incidence of submucosal invasive carcinoma in each type (Type 1, Type 2 and Type 3) were 0% (0/154), 7% (16/226) and 15% (38/256), respectively. The incidence of submucosal deep invasive carcinoma [≥1000 mm] in Type 3 was higher than that in Type 2 (11% [29/256] vs 3% [7/226], p < 0.05).

Conclusion: This subclassification for LST-G according to the diameter of granules and nodules using chromoendoscopy with indigo carmine dye spraying was universal, and may be clinically useful for choosing therapeutic strategy.

Disclosure of Interest: None declared

P1040 LOW RATE DETECTION OF ADVANCED ADENOMAS WITH A SINGLE-SAMPLE FECAL IMMUNOCHEMICAL TEST IN AVERAGE-RISK INDIVIDUALS: A PROSPECTIVE PILOT STUDY USING COLONOSCOPY AS REFERENCE STANDARD

L. Pereyra¹, E. J. Gómez¹, M. Omodeo¹, D. La Salvia¹, C. M. Godoy¹, R. González¹, J. M. Mella¹, C. Fischer¹, G. N. Panigadi¹, M. Bun², S. Lencinas², R. Miravalle³, U. Gualdrini³, D. G. Cimmino¹, S. C. Pedreira¹, L. A. Boerr¹

¹Gastroenterology and Endoscopy Unit, ²Colorectal Section, Surgery, Hospital Alemán, ³Centro Privado de Coloproctología, Buenos Aires, Argentina

Contact E-mail Address: lisandro_pereyra@hotmail.com

Introduction: Fecal immunochemical test (FIT) have been recommended for colorectal cancer (CRC) screening in several clinical practice guidelines and is the initial option in same regions due to limited availability or high costs of colonoscopy. However some studies have reported inconsistent results about FIT performance.

Aims & Methods

Aim: To compare the results of single-sample FIT with colonoscopy findings and calculate the accuracy for advanced neoplastic lesions or CRC detection.

Methods: Asymptomatic average-risk individuals scheduled for screening colonoscopy were invited to provided one stool sample one week before the exam. We used a cualitative FIT manufactured by ABONTM Biopharm (Hangzhou) co., Ltd., without diet or medication restrictions. The lower limit of haemoglobin detected by this test is 50 ng/ml. The positivity rate of the FIT in relation to colonoscopic findings and the accuracy (sensitivity, specificity, area under ROC curve) of the FIT for CRC and advanced neoplastic lesions detection were determined.

Results: Of a total of 146 individuals invited, 119 (81.5%) returned the FIT kit with adequate stool sample and completed their colonoscopy. Mean age was 58.4 (33-85) years and 58.8% were males. An advanced neoplasm was found in 14 (11.7%) individuals: a CRC in 2 (1.7%) and an advanced adenoma (>10 mm, villous histology or high grade dysplasia) in 12 (10.1%) subjects. In 31 individuals (26%) the FIT was positive. The positivity rate of the test in relation to colonoscopic findings was: 24.5% in patients with normal colonoscopy, 17.6% in hyperplastic polyps, 20% in sessile serrated adenomas, 25.8% in adenomas, 36.4% in advanced adenomas, and 100% in CRC. The sensitivity and specificity of the FIT (95% confidence intervals) for advanced adenomas or CRC was 50% (25% to 75%) and 77% (74% to 80%) respectively. The area under ROC curve was 0.99. FIT sensitivity for CRC was 100% (20% to 100%), whereas specificity was 75% (74% to 76%). For advanced adenomas, sensitivity was 42% (17% to 70%) and specificity 76% (73% to 79%).

Conclusion: In this preliminary report of a single-sample FIT before screening colonoscopy, the positivity rate was significantly high (26%) but the test only detected little more than a third of advanced adenomas. However all CRC were detected (sensitivity 100%).

Disclosure of Interest: None declared

P1041 CLINICAL EVALUATION OF UNEXPECTED COLONIC FOCAL UPTAKE DETECTED BY FDG-PET/CT

M. Ishihara¹, M. Tajika¹, T. Tanaka¹, N. Mizuno², K. Hara², S. Hijioka², H. Imaoka², N. Hieda², N. Okuno², T. Yoshida², K. Yamao², Y. Niwa¹

¹Endoscopy, ²Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan

Contact E-mail Address: mishihara@aichi-cc.jp

Introduction: FDG-PET/CT is recognized as a useful tool to manage colorectal cancer and has been shown to have an additional value in the detection of colorectal cancer recurrence. Some studies reported that FDG accumulated in adenomatous polyps, and the possibility that FDG-PET/CT can detect early premalignant colorectal lesions was suggested. However, few studies have evaluated FDG-PET/CT for incidental premalignant colonic lesion detection.

Aims & Methods: FDG PET/CT studies were performed for two-year periods in 5088 consecutive patients with various malignant diseases. We retrospectively analyzed the records of 240 consecutive patients who had undergone colonoscopy and FDG-PET/CT scan for malignant disease from December 2012 to November 2014 at our hospital; colonoscopy and FDG-PET/CT were done within six months of each other. Patients with a previous history of colorectal cancer were excluded from analysis.

Results: Seventy-four patients had 86 foci of incidental colonic activity on PET and were designated Group A (mean age 67.0 years, males 66%). The other 166 patients had no incidental colonic foci and were designated Group B (mean age 63.6 years, males 65%). The locations of colorectal foci were in the right side in 25 patients, in the left side in 41 patients, and in the rectum in 20 patients. In group A, 26 patients (35%) had malignant tumors (22 colorectal cancers, three malignant lymphomas, and one metastatic tumor) detected on colonoscopy. In group B, three patients (2%) had malignant tumors (two colorectal cancers and one metastatic tumor). Overall, the sensitivity, specificity, PPV (positive predictive value), NPV (negative predictive value), and accuracy of PET-CT for detecting malignant colonic tumors were 90%, 77%, 35%, 98%, and 79%, respectively. For detecting malignant colonic tumors and adenomas 10 mm or more in diameter, the sensitivity, specificity, PPV, NPV, and accuracy of PET-CT were 84%, 86%, 66%, 95%, and 86%, respectively.

Conclusion: FDG-PET/CT is a useful tool for detecting both malignant colorectal tumors and adenomas 10mm or more in diameter. Incidental colonic activity detected by PET-CT warrants further evaluation with colonoscopy. However, negative PET-CT does not rule out malignant colorectal tumors.

Disclosure of Interest: None declared

P1042 THE POSSIBILITIES OF THE OPTICAL METHODS FOR THE STUDY OF BLOOD IN COLORECTAL CANCER STAGING DIAGNOSING

M. V. Kruchinina¹, A. Starikov², S. Kurilovich¹, A. Gromov¹, V. Kruchinin³, S. Rykhlitsky³, V. Generalov⁴, V. Volodin³, S. Peltec⁵, S. Shehovtsov⁵

¹Siberian Branch Russian Academy of Medical Sciences, Federal State Budgetary Institution of Internal and Preventive Medicine, ²Regional Oncology Center, ³Siberian Branch Russian Academy of Sciences, Institute of Semiconductor Physics, ⁴Federal Budgetary Research Institution, “State Research Сenter of Virology and Biotechnology “Vector”, ⁵Siberian Branch Russian Academy of Sciences, Institute of Cytology and Genetics, Novosibirsk, Russian Federation

Contact E-mail Address: kruchmargo@yandex.ru

Introduction: Colorectal cancer (CC) is the second most common form of cancer in the world. The limitations of the currently available methods and biomarkers for CC management highlight the necessity of finding novel markers.

Aims & Methods: The aim of this work was to assess the potential of the optical methods for studying erythrocytes (Er) and blood serum (BS) of patients with CC in staging diagnosing.

A total of 36 persons (53±9 years old) with CC (histologically – adenocarcinoma) in the T1-2 stage (the 1^st group) and in the stage T3-4 (the 2^nd group) were examined. The control group consisted of 16 healthy people. Electric and viscoelastic Er parameters were investigated by dielectrophoresis, their membrane structure - by TLC and gas chromatography. The optical properties of BS were studied by the methods of ellipsometry. The reaction of the monoclonal antibody CD 24 with BS antigens of CC patients was studied by spectroscopic ellipsometry close to the conditions of surface plasmon resonance (SPR) (ProteOn XPR36 (BioRad).

Results: We observed differences in Er parameters, associated with the CC stage. Given in the 2nd group summarized rigidity, viscosity, electrical conductivity, the relative polarizability, indexes of aggregation and destruction were higher than those in the 1^st and in the controls (p < 0.001-0.05). At the same time the patients of the 2nd group had marked disturbances of Er deformability, leading to the development of microcirculatory disorders and tissue hypoxia. We observed high levels of cholesterol fraction, oleic, stearic acids, high index of cholesterol/phospholipids (PHL) and low levels of total lipids, easily oxidable PHL, arachidonic acid, omega-3 index in Er membranes in the 2nd group in comparison with those in the 1^st group of patients (p < 0.0001-0.03). Scanning ellipsometry showed marked heterogeneity in thickness and composition, the abundance of discontinuities in thin films of BS of patients in the 2nd group compared to the 1^st one (p < 0.001). Increasing the refractive index in combination with the reduction in film thickness as CC stage was weighting has been observed (p < 0.01-0.05). The concentration of the antigens to the CD24 in the BS of patients (obtained by SPR) in the terminal stages of CC was higher than that in the T1-2 (p < 0.001). We revealed correlations between Er parameters, BS ellipsometry characteristics and biochemical parameters, which reflected the interaction between these components depending on the CC stage.

Conclusion: Identified microcirculatory disturbances probably aggravate the course of CC and, therefore, require additional therapeutic effects. Differences in Er and BS parameters associated with the stage of CC, give hope for the development of new diagnostic methods at the early stages of the disease.

Disclosure of Interest: None declared

P1043 CHARACTERIZATION OF THE ENDOSCOPIC AND PATHOLOGIC MEASUREMENTS OF COLORECTAL POLYP SIZES AND ITS ASSOCIATION WITH POST-POLYPECTOMY COLONOSCOPY SURVEILLANCE GUIDELINES

M. N. Costa¹, V. Pavão Borges¹, T. Capela¹, P. Russo¹, C. Bernardes¹, D. Carvalho¹, M. J. Silva¹, R. Loureiro¹, J. Esteves¹, A. David Marques¹

¹Gastroenterology, Hospital de Sto. António dos Capuchos - Centro Hospitalar de Lisboa Central, Lisbon, Portugal

Contact E-mail Address: mariananunocosta@gmail.com

Introduction: Colorectal cancer (CRC) is the main leading cause of cancer related deaths in Portugal. After removing colorrectal polyps (CRPs), ESGE[1], ASGE[2] and UK guidelines[3] recommend endoscopic surveillance based on size, number and histological findings of CRPs. While UK guidelines use the endoscopical measured size (EMS), the preferred method (endoscopical versus histological) for CRP size assessment is not specified in the ESGE and ASGE guidelines. The preferred CRP size assessment method is controversial.

Aims & Methods: To characterize the discordance and correlation between the pathological measured size (PMS) and EMS of CRPs, according to its anatomic location and histological findings.

All colonoscopies in which CRPs were observed between 1/Jan/2013 and 31/Dec/2013 were identified. CRPs removed by polypectomy snare in a single fragment and with available endoscopic and histological reports were selected. The endoscopic and pathologic measurements of CRPs sizes were performed.

Results: The PMS (mean 8.03 mm ±1.41 SD) was significantly smaller than the EMS (mean 10.46 mm ±7.36 SD) in the 552 CRPs included in the study (360 patients, 68.6% male, years median 69), independently of anatomic location (right colon, transverse colon or left colon + rectum) and EMS sub-group (≥1cm or <1cm). There was a good correlation between the EMS and PMS in the adenomas (ĸ=0.807, 95% confidence intervals [CI]) and a moderate correlation in the serreated polyps (SP) (ĸ=0.647, 95% CI). However, 32.0% of the adenomas and 63.2% of the SPs with EMS ≥ 1 cm presented PMS < 1 cm.

Conclusion: In a considerable portion of adenomas and SP where EMS is >1 cm, the PMS is <1 cm. This divergence may lead to alternative colonoscopy surveillance intervals after polypectomy, which may have both clinical and economic implications.

Disclosure of Interest: None declared

P1044 SCREENING COLONOSCOPY FOR SUBJECTS OLDER THAN 85 YEARS OLD

M. Kato¹, E. Sakaguchi¹, K. Abe¹, Y. Takada¹, T. Hirata¹, S. Banno¹, M. Wada¹, Y. Takatori¹, S. Kinoshita¹, H. Kikuchi², K. Takabayashi¹, M. Kikuchi¹, M. Kikuchi¹, Y. Fujiyama¹, T. Ohishi², T. Uraoka¹

¹Department of Gastroenterology, ²Department of Surgery, National Hospital Organization, Tokyo Medical Centre, Meguro-ku, Tokyo, Japan

Contact E-mail Address: moto28hiko@icloud.com

Introduction: According to US multi societies guideline for colonoscopy surveillance after screening and polypectomy, subjects elder than 85 are recommended to stop undergoing colonoscopy. However, asymptomatic elder subjects often come to hospital only due to positive fecal occult blood test in Japan with population aging.

Aims & Methods: This study was aimed to evaluate safety and efficacy of colonoscopy for subjects elder than 85 years old. This is a retrospective cohort study. From April 2006 to March 2010, 265 subjects elder than 85 years old underwent colonoscopy at our hospital. Of them, 16 patients who underwent surveillance after surgery for colorectal cancer and 54 patients who had been already pointed out some abnormalities were excluded and total 195 subjects were included for analysis. The subjects were divided into screening groups who were free from symptoms (hemoglobin <10g/dL, abdominal pain, or hematochezia) and symptomatic group. The association between detection rate of advanced colorectal cancer and various background factors (age, sex, presence or absence of symptom, hemoglobin, or mean corpuscular volume (MCV) using Logistic Regression model. Factors which revealed statistical tendency (p <0.10) were included multivariate multivariate analysis. Cumulative overall survival rate of patients with advanced colorectal cancer was calculated using Kaplan-Meier method.

Results: There were 47 asymptomatic subjects and 148 symptomatic subjects. Advanced colorectal cancer was detected in 6.5% of asymptomatic and in 17% of symptomatic subjects respectively (p=0.0946). Low MCV revealed significance, and to be female (p=0.706) and presence of symptom (p=0.0581) revealed marginal significance for detection of advanced cancer. In multivariate analysis, only low MCV was independent risk factor (Odds ratio (every 5 decrease) 1.63 [1.29-2.11]). The cumulative overall survival rate at 3 and 5 years of patients with advanced colorectal cancer was 76% and 62%, respectively.

Conclusion: Colonoscopy for symptomatic patients would not be a contraindication because prognosis of advanced colorectal cancer was not so poor in our study. MCV might be a useful predictor for determination of the indication of colonoscopy for extremely elderly subjects.

Disclosure of Interest: None declared

P1045 LONG TERM ONCOLOGIC OUTCOMES OF THE COLORECTAL TIS CANCER

J. Hyun¹, H. Chang¹, D. Sohn¹, K. Han¹, B. Kim¹, J. Oh¹, C. Hong¹

¹National Cancer Center, Republic of Korea, Goyang-si, Republic of Korea

Contact E-mail Address: hj11542@naver.com

Introduction: The incidence of early colorectal cancers is on rise with increase of screening colonoscopy. Thus, risk factors of lymph node metastasis or recurrence in early colorectal cancer is also important medical issue for endoscopists and colorectal surgeons.

Aims & Methods: The aim of this study was to evaluate that the depth of invasion in Tis cancer was associated with recurrence or lymph node metastasis. Additionally, this study was to assess the long-term outcome of patients with colorectal Tis cancer. A total of 496 colorectal Tis cancers from 481 patients between March 2003 and December 2013 were analyzed retrospectively. We evaluate the pathologic and clinical risk factor of colorectal Tis patients.

Results: The mean age of study population was 64.7 years and the median follow up time was 30.3 months. Of a total of 496 Tis cancers. There were no radiological lymph node metastases in 177 patients who conducted the computed tomography. 1.2% of Tis cancer showed angiolymphatic invasion. Three patients (0.62%) had proven distant or local recurrence. Local recurrences were occurred in 2 patients. And one patient who had peritoneal seeding and ovarian metastasis showed positive resection margin and tumor invading lamina propria at primary resection.

Conclusion: 1.2% of colorectal Tis cancer had positive results of angiolymphatic invasion. In recurrence cases what it were too small, all of recurrence patients had positive margin after resection. Thus, clinicians pay attention to angiolymphatic invasion and positive resection margin in pathologic results of colorectal Tis cancer after treatment.

Disclosure of Interest: None declared

P1046 EFFECTIVENESS AND SAFETY OF COLORECTAL ESD IN ELDERLY PATIENT

K. Ashikari¹, H. Chiba¹, D. Kurihara¹, T. Suto¹, N. Kawano¹, M. Kaai¹, S. Seki¹, A. Takahashi¹, T. Ida¹, T. Morohashi¹, T. Goto¹

¹Gastroenterology, Omori Red Cross Hospital, Tokyo, Japan

Introduction: Colorectal endoscopic submucosal dissection (ESD) has been established as a useful treatment for early colorectal tumors. The prognosis of early colorectal cancer is expected over several years without treatment. However, elderly people who often have various comorbidities might die of any other diseases, so colorectal ESD for elderly people is still controversial.

Aims & Methods: To analyze the potential benefits and risks of colorectal ESD in elderly compared to younger patients, we analyzed patients retrospectively who underwent ESD for early colorectal cancer in Omori Red Cross Hospital from 2012 May to 2015 March. We divided the patients into two groups: patients older than 80 years (group A) and patients 79 years of age or younger (group B). The two groups were compared with respect to their clinical backgrounds, medication (antiplatelet, anticoagulation), tumor characteristics, operation time, resection speed (mm²/min), complication, rate of en bloc or curative resection, and survival rate. Statistical analysis included univariate analysis by chi-squared tests and Student's t-tests for comparing two groups (statistical significance was defined as p < 0.05).

Results: 156 lesions (male/female:81/75) underwent ESD procedures; 27 in group A and 129 in group B. Group A had significantly more comorbid diseases (hypertension, diabetes, renal or liver dysfunction, cardiac disorder) than group B (55.6% vs. 24.8%, p < 0.01). Patients in group A tended to take more antithrombotic medication than group B (22.2% vs. 11.6%, p=0.14). Tumor size, specimen size, operation time, resection speed (mm²/min), rate of complete en bloc resection, rate of curative resection, complication and survival rate were similar: 29.4 ± 18.2mm, 37.8 ± 18.3mm, 43.9 ± 35.6min, 25.8 ± 13.8(mm²/min), 27/27 (100%), 27/27 (100%), 0/27 (0%), 26/27 (96.3%) in group A, and 29.1 ± 15.4mm, 37.6 ± 16.9mm, 44.3 ± 45.1min, 28.0 ± 15.3 (mm²/min), 128/129 (99.2%), 124/129 (96.1%), 2/129 (1.6%), 128/129 (99.2%) in group B, respectively. Perforation occurred in 2 cases in group B. There were no differences in hospitalization periods and post-operative clinical courses between two groups. All of the 5 non-curative cases in group B are alive at the end of the follow up period (average 17.0 months. range: 6-28). Only one of 27 patients in group A died suddenly of heart failure about 1 month after the colorectal ESD, and the others are alive at the end of the follow up period (average 13.6 months. range: 1-32).

Conclusion: Colorectal ESD is almost equally effective and safe both in elderly and in younger patients. However, elderly patients have more comorbid diseases and tend to have more antithrombotic agents. Therefore, preoperative assessment of comorbid conditions and adequate perioperative care are necessary for elderly patients. Furthermore, to evaluate the exact prognosis of elderly patients performed colorectal ESD, we should continue to follow up them in longer period.

Disclosure of Interest: None declared

P1047 THE VALIDITY OF THREE STEPS LEARNING SYSTEM OF COLORECTAL ESD

K. Ashikari¹, H. Chiba¹, D. Kurihara¹, T. Suto¹, N. Kawano¹, M. Kaai¹, S. Seki¹, A. Takahashi¹, T. Ida¹, T. Morohashi¹, T. Goto¹

¹Gastroenterology, Omori Red Cross Hospital, Tokyo, Japan

Contact E-mail Address: kei-pushi-1@hotmail.co.jp

Introduction: Endoscopic submucosal dissection (ESD) for early colorectal cancer has become a widespread treatment over the world, but severe complications are reported still now and the appropriate training system of colorectal ESD is controversial.

Aims & Methods: In our hospital, the qualifications of an ESD trainee (A) are 1000 upper/300 lower endoscopy, 30 gastric ESD, and 20 colorectal ESD assistance. Colorectal ESD is performed with support by an expert (B) following these 3 steps. a) 0-5 cases: the position is all rectum, and have no fibrosis (F0), b) 6-20cases: tumor size is ≤50mm with no or mild fibrosis (F0/F1) and the expert gives every possible advices during procedures, c) 21cases-: The expert gives important advices or hands-on support only when the situation has technical difficulty or the trainee does dangerous procedure. We call this method “Three steps learning system (TSLS)’’. 154 consecutive ESD procedures performed in Omori Red Cross Hospital from 2012 April to 2015 March were retrospectively analyzed. We evaluated clinical backgrounds, outcomes of ESD procedures, and complications.

Results: A/B performed 23/131 cases respectively. The mean age, sex, comorbid diseases (hypertension, diabetes, renal dysfunction, cardiac disease), rate of having antithrombotic agents were similar between two groups. The location was C3/A1/T5/D3/S3/R8 in group A and C20/A24/T25/D17/S16/R29 in group B (p=0.578). In terms of tumor shape, there was no protruded tumor in group A. There were also no significant differences in specimen size, tumor size, en bloc resection rate, and complication: 40.9 ± 23.3mm, 30.3 ± 20.4mm, 100%, and 1 case (perforation) in group A and 37.1 ± 16.0mm, 29.0 ± 15.2mm, 99.2% (130/131), and 1 case (perforation) in group B, respectively. Meanwhile, operation time and speed of resection (that is specimen size (mm²) / operation time (min)) in group B were much faster than group A: 73.0 ± 52.6min, 16.1 ± 8.7mm²/min in group A and 38.3 ± 39.1min, 29.9 ± 15.0mm²/min (p<0.01). The rate of fibrosis was 13.0% (F0/F1/F2: 20/3/0) in group A, 26.0% (F0/F1/F2: 97/29/5) in group B (p=0.18). Self-completion rate was 18/23 (78.3%) in group A. In group A, five cases were not self-completion and the factors were followings: with fibrosis, lesion at a fold, invaded submucosa, or large lesion (≥10cm). R0 resection rate were similar, 95.7% (22/23) in group A, and 96.9% (127/131) in group B. Of the five non-curative resection cases, 4 cases were performed additional operation, and 1 case chose a conservative course. The clinical courses after procedures (fever, WBC, CRP) were also similar.

Conclusion: The advices of experts are very important for keeping safety ESD and an independence of novice is also essential. Colorectal ESD under our training system (TSLS) was appropriate and safe. However, in this study, there were few difficult lesions in group B. For verifying the validity of our system or improving self-completion rate, more cases will be required.

Disclosure of Interest: None declared

P1048 ADJUVANT CHEMOTHERAPY WITH TEGAFUR-URACIL PROVIDED GOOD OUTCOME FOR LOW-RISK STAGE II COLON CANCER

K. C. Hsiao¹, J. M. Hu¹

¹Colon and Rectal Surgery, Tri-Service General Hospital, Taipei, Taiwan, Province of China

Contact E-mail Address: dr.hsiao@msa.hinet.net

Introduction: The benefit of adjuvant chemotherapy with Tegafur-uracil for the low-risk patients of stage II colon cancer is still uncertain. Our primary aim is to determine the outcome of disease free survival (DFS) and 5-year overval l survival (OS) provided by adjuvant chemotherapy using Tegafur-uracil for stage II colon cancer.

Aims & Methods: From January 2004 to December 2011, 404 low-risk stage II colon cancerpatients received curative operation in a single medical center. The clinical data were extracted from the retrospectively collected colon cancer database. The patients were divided to adjuvant chemotherapy with Tegafur-uracil, adjuvant chemotherapy with 5-fluorouracil and radical surgery alone. The DFS curves and OS curves were calculated with Kaplan-Miere’s analysis.

Results: Among the 404 low-risk stage II colon cancer patients, 180 (44.6%) had adjuvant chemotherapy with Tegafur-uracil, 79 (19.5%) received adjuvant chemotherapy with 5-fluorouracil, and 145 (35.9%) underwent radical surgery alone. Within the median of 49 months follow-up, recurrence developed in 36 patients (8.18%). However, patients who received adjuvant chemotherapy with Tegafur-uracil had improved OS compared to others who underwent surgery alone. Multivariate analysis showed that only adjuvant chemotherapy with Tegafur-uracil >1 year (P=0.001) was independent factors for DFS. Moreover, only age <70 years (p=0.043) and chemotherapy with Tegafur-uracil (p=0.001) related good OS.

Conclusion: We suggested adjuvant chemotherapy with Tegafur-uracil, especially consecutive administration more than one year, providing good DFS and OS for the low-risk patients of stage II colon cancer after radical surgery.

Disclosure of Interest: None declared

P1049 CLINICAL OUTCOMES OF RECTAL NEUROENDOCRINE TUMORS TREATED BY ENDOSCOPIC RESECTION

M. Takita¹, K. Ohata¹, Y. Misumi¹, H. Tsunashima¹, T. Tashima¹, Y. Minato¹, E. Sakai¹, T. Muramoto¹, Y. Matsuyama¹, K. Nonaka¹, N. Matuhashi¹

¹Gastroenterology, NTT Medical Center Tokyo, Tokyo, Japan

Contact E-mail Address: myc0p1asm@mail.goo.ne.jp

Introduction: According to 2010 WHO classification, neuroendocrine tumors (NET) are classified into three categories (G1, G2 and G3). Of these tumors, G1 NET smaller than 10 mm, mainly located at the rectum, metastasize only rarely, and thus can be treated by endoscopic resection. However, complete resection is occasionally difficult due to their localization in the submucosal layer. In addition, even NET smaller than 10mm might have lymphovascular invasion. We conducted this retrospective study to evaluate the risk of recurrence after endoscopic treatment and to search for a suitable treatment of rectal NET.

Aims & Methods: Between January 2005 and March 2014, 137 patients with 139 rectal NET lesions underwent endoscopic treatment in our hospital. Firstly, we investigated complete and curative resection rate of EMR (EMR/EMR-C/EMR-L) and ESD groups. We defined curative resection as complete resection, smaller than 10mm, and lack of microscopic lymphovascular invasion. Resection that fail to meet either of the above three criteria was defined as non-curative. When additional surgical resection was performed, the rate of positive histological lymph node metastasis was calculated. Subsequently, we investigated long-term outcomes of endoscopic resection for rectal NET.

Results: Most of the tumors were located at Rb (80%), and the median diameter was 5.7 mm. Numbers of cases treated with EMR/EMR-C/EMR-L/ESD were 10/3/114/12. Of the 139 tumors, 129 achieved complete resection (93%). Regarding the 10 incomplete resection cases, the treatments were EMR, EMR-C, and ESD in 5, 1, and 4 cases, respectively. No tumors presented muscular invasion. 79 lesions (57%) achieved curative resection, and no recurrence was identified in this group during the follow-up periods (median 27 months). 53 of the 60 lesions with non-curative resection were followed without additional resection, but no case had recurrence during the follow-up period (median 42 months). Seven of the non-curative resection cases underwent additional resection, among whom one case had lymph node metastasis; in that case, the tumor was larger than 10mm, positive for vascular invasion, and the treatment was incomplete resection. As a whole, recurrence was identified in none of the total 139 cases during the follow-up period (median 33 months). Focusing on adverse events, 10 delayed bleedings occurred (5 EMR, 4 EMR-C and 1 ESD cases), and one perforation occurred in a patient undergoing ESD.

Conclusion: EMR-L is generally thought to be a feasible measure as an endoscopic treatment of rectal NET, even though delayed bleeding rate is relatively high. Current curative criteria including complete resection, smaller than 10mm, and no lymphovascular invasion is considered to be appropriate in that cases meeting the criteria can be regarded as cured. However, given that there was no recurrence without additional resection in cases regarded as “non-curative” resection, mainly due to lymphovascular invasion and/or larger size, observation without additional resection might be allowed, although the observation period was not long enough in the present analysis. To establish curative criteria and indication for endoscopic treatment, further studies including those with longer follow-up periods are needed.

Disclosure of Interest: None declared

P1050 MAGNIFYING CHROMOENDOSCOPY IS DECISIVE TO DEFINE MANAGEMENT OF COLORECTAL NEOPLASTIC LESIONS

F. S. Kawaguti¹, M. C. Franco¹, C. M. P. S. Pennacchi¹, B. D. C. Martins¹, F. A. Retes¹, C. F. Marques¹, C. S. Nahas¹, A. V. Safatle-Ribeiro¹, U. Ribeiro Jr¹, S. C. Nahas¹, F. Maluf-Filho¹

¹São Paulo Cancer Institute, São Paulo, Brazil

Contact E-mail Address: mcavalcantefranco@gmail.com

Introduction: Early colorectal cancer with submucosal deep invasion should not be treated by endoscopic resection due the high risk of lymph-nodes metastases. Magnifying chromoendoscopy and evaluation of pit pattern can predict the malignant potential of colorectal lesions. Accurate diagnosis of lesions allows indication of the best treatment, endoscopic or surgical.

Aims & Methods: Evaluate efficacy of magnifying chromoendoscopy in the definition of management of colorectal neoplastic lesions. Between April 2009 and August 2014, patients with colorectal neoplastic lesions with high risk of submucosal invasion (sessile ≥ 20 mm, depressed type and LST-type lesions) underwent magnifying chromoendoscopy. The therapeutic approach (endoscopic or surgical) was defined according to the endoscopic evaluation. Lesions with Vn pit pattern were referred to surgical resection. Lesions without Vn pit pattern were referred to endoscopic treatment and the decision of therapeutic approach was according to pit pattern, location and size. Final staging was possible with the histology of the surgical or endoscopic specimen. Lesions that were not resected or those where it was not possible to visualize the pit pattern due eroded surface were excluded.

Results: A total of 104 lesions were found in 103 patients (47% male, mean age of 64.4 years-old). Six lesions were excluded. The average size of lesions was 45.1 ± 31.9 mm. The macroscopic classification was 15.3% sessile, 4.1% depressed and 80.6% LSTs. The endoscopic treatments were polypectomy in 2.0%, EMR in 15.3%, EPMR in 13.3%, ESD in 45.9% and TEM in 9.2%. Surgical resection was referred in 14.3% of the lesions. The correlation of pit pattern with pathology was:- II: 100% adenomas with low-grade dysplasia (2/2)- IIIL: 69.2% of low-grade adenoma (9/13)- IIIS: 100% intramucosal adenocarcinoma (1/1)- IV: 72.0% of adenoma with high-grade dysplasia or intramucosal adenocarcinoma (18/25)- Vi: 86.9% of intramucosal adenocarcinoma or superficial submucosal invasion <1000 μm (40/46) / 6.5% adenocarcinoma with massive submucosal invasion> 1000 μm (3/46)- Vn: 54.5% of adenocarcinoma with massive submucosal invasion (6/11); 45.5% of adenocarcinoma with invasion to the muscularis propria. The therapeutic indication based on magnifying chromoendoscopy and pit pattern classification was considered correct in 96.9% of cases (95/98). Three cases Vi pit pattern lesions were endoscopically resected and the histology demonstrated massive submucosal invasion. These patients were sent to surgical resection. Magnifying chromoendoscopy and pit pattern classification had a 78.6% sensitivity, a 100% specificity, a 100% predictive positive value, a 96.6% negative predictive value and a 96.9% accuracy to detect submucosal massive invasion, or deeper.

Conclusion: Magnifying chromoendoscopy is accurate to detect submucosal massive invasion, or deeper, of colorectal neoplastic lesions which allows correct selection of patients to surgical or endoscopic resection. The Vn pit pattern contraindicates endoscopic resection.

Disclosure of Interest: None declared

P1051 ENDOSCOPIC MANAGEMENT AND CLINICAL OUTCOMES OF MALIGNANT COLORECTAL POLYPS

M. W. Jung¹, S. J. Shin¹, K. M. Lee¹, S. G. Lim¹

¹Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea

Contact E-mail Address: jmw_81@hanmail.net

Introduction: The endoscopic management of colorectal polyps containing adenocarcinoma is increasing in nowadays due to colorectal cancer screening programs. The aim of this study was to evaluate the safety and efficacy of endoscopic resection of malignant colorectal polyps.

Aims & Methods: Patients who underwent endoscopic resection for colorectal polyps which containing adenocarcinoma from August 2001 to July 2014 in Ajou university hospital of Korea. The data were retrospectively reviewed. Clinical outcomes such as complete resection rate, recurrence rate, complications were analyzed.

Results:

Table1.

Relationships between recurrence and complete resection status, risk of polyps

	Recurrence after polypectomy		p value
	No	Yes
Complete resection (CR)
CR (n=266)	258 (97.0%)	8 (3.0%)
ICR (n=143)	130 (90.9%)	13 (9.1%)	0.008
Risk of malignant polyp
Low risk (n=252)	245 (97.2%)	7 (2.8%)
High risk (n=157)	143 (91.1%)	14 (8.9%)	0.020
Total	388	21	409

Total 482 polyps in 462 patients were analyzed in this study. 444 lesions were resected by snaring polypectomy including endoscopic mucosal resection (EMR) and 38 lesions by endoscopic submucosal dissection (ESD). The high risk malignant polyps were defined as having: tumor invasion in the margin or an uncertain margin; poor differentiation (WHO classification grade III); or invasion of lymphatic or venous vessels. Low risk malignant polyps did not have any of these three histological signs. We analyzed the recurrence rate of the 409 lesions followed up for at least 3 months. The recurrence rate was 5.1% (21/408), and it was affected by complete resection status (p=0.008) and risk of polyps (p=0.006). Procedure-related complications developed in 20 lesions; perforations in 8 lesions (1.7%) and significant bleedings required additional endoscopic procedure in 12 lesions (2.5%).

Conclusion: Endoscopic polypectomy could be adequate and effective treatment for patients with malignant colorectal polyps, especially low-risk polyps.

Disclosure of Interest: None declared

P1052 TERPINEN-4-OL: A NOVEL AND PROMISING THERAPEUTIC AGENT FOR HUMAN COLORECTAL CANCER TERPINEN-4-OL

N. Arber¹, S. Shapira¹, S. Pelban¹

¹Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

Contact E-mail Address: shiranshapira@gmail.com

Introduction: Background: Monoterpenes are major secondary metabolites present in plants and known to be associated with the plant defense mechanisms. Terpinen-4-ol is a naturally occurring monoterpene, found in the essential oils of many aromatic plants and is the main bioactive component of tea tree oil. It has been shown to have antiviral, antibacterial, antifungal, and insecticidal effects as well as anti-oxidant and anti-inflammatory activities. It was demonstrated to induce primary necrotic cell death and cell cycle arrest in melanoma and non-small cell lung cancer cells.

Aims & Methods

Aim: To study the antitumor effects of terpinen-4-ol and its mechanism of action in various types of GI malignancies, alone and in combination with several chemotherapeutic and biological agents.

Methods: Terpinen-4-ol was administrated alone or combined with standard anti-CRC agents including, oxaliplatin, fluorouracil (5-FU), cetuximab and bevacizumab. It was also combined with humanized anti-CD24 monoclonal antibodies previously developed in our lab (Shapira Gastro 2011). Killing effects were measured qualitatively by light microscopy and quantitatively using the MTT assay. The in vivo toxicology, LD₅₀ value, of various doses of Terpinen-4-ol was tested following several routes of administration (oral, intramuscular, topical, and by subcutaneous and intra-peritoneal injection). Subcutaneous tumors were produced by injection of 5x10⁶ of DLD-1 CRC cell lines into nude mice. When the tumors reached a dimension of 5 mm, the animal’s treatment was initiated.

Results: The LD₅₀ value of Terpinen-4-ol after intra-peritoneal injection in mice is 120 mg/kg body. Terpinen-4-ol induces a significant growth inhibition of CRC cell lines, including HCT116, DLD1 and COLO320, in a dose-dependent manner. Terpinen-4-ol and various anti-cancer agents (0.2 µM oxaliplatin, 0.5 µM fluorouracil (5-FU), 1 µM cetuxumab and 50 µM bevacizumab) demonstrated a synergistic inhibitory effect of cancer cell proliferation. Subtoxic concentrations of terpinen-4-ol potentiate anti-CD24 mAb-induced growth inhibition. The anti-tumor activity of terpinen-4-ol alone or in combination with cetuxumab was evaluated. Considerable reduction in tumor volume was seen following terpinen-4-ol (0.2%) treatment alone and in combination with cetuxumab (10 mg/kg) (40% and 63%, respectively) in comparison to the control group that received PBS (+DMSO).

Conclusion: Terpinen-4-ol significantly enhances the effect of several anti-cancer agents, including chemotherapeutic and biological drugs, in particular therapeutic antibodies. The possible molecular mechanism for the activity of Terpinen-4-ol involves induction of cell death rendering this compound as a potential anticancer drug alone or in combination, for the treatment of a wide range of malignancies (was tested on pancreatic, prostate and stomach), including CRC.

Disclosure of Interest: None declared

P1053 SELECTIVE CYCLOOXYGENASE-2 INHIBITOR ATTENUATES PRO-METASTATIC AND ANTI-APOPTOTIC EFFECTS OF ENDOTOXIN-LIPOPOLYSACCHARIDE

O. Plehutsa¹, R. Sydorchuk², L. Sydorchuk², I. Sydorchuk²

¹District Hospital, Briceni, Moldova, Republic of, ²Bukovinian State Medical University, Chernivtsi, Ukraine

Contact E-mail Address: supers_stars@uni.de

Introduction: Growing evidence indicates that bacterial infections and following inflammation is contributing to cancer growth. Recent studies showed promotional influence of endotoxin-lipopolysaccharide (LPS) on cancerogenesis and metastatic growth, which in part is associated with involvement of cyclooxygenase-2 (COX-2). Elevated tumour COX-2 is associated with increased angiogenesis, tumour growth and promotion of tumour metastasing and resistance to apoptosis. The mode of action of COX-2 and its inhibitors remains unclear. We hypothesized that inhibiting of COX-2 may decrease inflammation contributing to metastatic growth.

Aims & Methods: Murine model including 2 groups (25 each) of adolescent mice was used. Metastatic process was modeled by i/v injection of 200 µl spontaneously metastasizing mammary adenocarcinoma cell culture suspension. Both control and experimental group animals received 200 µl suspension of 10 µg LPS per mouse. Experimental group received selective COX-2 inhibitor celecoxib orally from day 1. Metastatic growth evaluated hystochemically within pulmonary metastases. TNF-α, VEGF quantified with ELISA; COX-2 with Western Immunoblotting.

Results: Control group mice developed a mean number of 35.27 ± 6.19 macroscopic metastases by day 15. Both the weight and quantitative parameters of metastatic growth were significantly lower in study group compared to control (p < 0.005-0.0001). Experimental group metastatic growth was characterized by 48.8% lower mitotic index (MI) and 37.6% higher apoptotic index (AI). MI/AI ratio in the experimental group was 2.1 times lower (p < 0.001) than the ratio observed in control group mice. Systemic COX-2, TNF-α and VEGF were significantly lower in celecoxib group (p < 0.005-0.001) compared to control.

Conclusion: It is becoming evident that selective COX-2 inhibitors have a growing potential as a beneficial target for chemopreventive and tumour regression for many cancers. Although expression of COX-2 has been associated with development and progression of numerous malignancies, its precise role in promotion of cancer cell dissemination is still poorly understood. TNF-α – a major proinflammatory cytokine is released in response to LPS associated increase of VEGF production via COX-2 pathway. Current study shows that pro-cancerogenic effect of endotoxin in experimental murine model could be inhibited by neutralizing COX-2 associated pathway. Treatment with celecoxib was effective in reducing metastasis volume, suggesting that COX-2 contributes to metastatic growth. However, there is no direct evidence that all metastases are/could be sensitive to COX-2 inhibition.

Disclosure of Interest: None declared

P1054 SHORT-TERM RESULTS OF COLORECTAL ENDOSCOPIC SUBMUCOSAL DISSECTION

O. Urban¹, P. Fojtik¹, P. Falt¹, M. Kliment¹

¹Gastroenterology, Vitkovice Hospital Ostrava, Ostrava, Czech Republic

Contact E-mail Address: ondrej.urban@nemvitkovice.cz

Introduction: Colorectal endoscopic submucosal dissection (CR-ESD) is accepted as a minimally invasive treatment for large (≥20 mm) neoplastic lesions. It is less invasive than surgery and provides higher en bloc resection rate than endoscopic mucosal resection (EMR). The purpose of this study is to evaluate short-term results of CR-ESD in a single western institution.

Aims & Methods: All patients treated by CR-ESD between November 2011 and October 2014 were included. CR-ESD was indicated according to the Japanese Colon ESD Standardization Implementation Working Group criteria and was performed by using Dual-knife and/or IT-knife nano. The complete resection of the lesion, en bloc resection, R0 resection, the curative resection, the 30- day mortality and complications were considered as short-term results.

Results: Among 43 patients, 32 (74.4%) were males and 11 (25.6%) were females. Mean age was 69. 6 (range 53-89) years. The mean lesion size was 24 (range 5-70) mm. From a total of 43 lesions, 32 (74.4%) were localized in the rectum, 8 (18.6%) in the distal colon and 3 (6.9%) in the proximal colon. The types of the lesions were as follows: 0-Is 7 (16.2%), LST-GH 2 (4.6%), LST-GM 7 (16.2%), LST-NG 3 (6.9%), LST-NGPD 11 (25.6%), 0-IIc 2 ( 4.6%), 0-IIa 2 (4.6%) and post-EMR residual lesion 9 (20.9%).

The complete resection of the lesion was achieved in 41 (95.3%) of cases. The 30-day mortality was none. En bloc, R0 and curative resection was achieved in 30 (69.8 %), 24 (55.8 %) and 24 (55.8 %) cases respectively. From a total of 5 (11.6 %) perforations 4 were closed by clips and one remaining required emergency surgery. In 2 (4, 6%) cases, perforation resulted in incomplete resection of the lesion. Delayed bleeding occurred in 2 (4.6 %) cases, both were managed endoscopically.

The final histology in cases with complete resection was as follows: LGIEN 5 (11.6%), HGIEN 17 (39.5%), intramucosal carcinoma 8 (18. 6%), T1 sm1 carcinoma 6 (13.9%), T1 sm2 and sm3 carcinoma 2 (4.6%), T2 carcinoma 1 (2.3%), neuroendocrine tumor 1 (2.3%) and xanthelasma 1 (2.3%).

Conclusion: Colorectal endoscopic submucosal dissection in our institution appears to be feasible and safe. Nevertheless, curative resection was achieved in 55.8% of cases only. This was caused mainly by high number of post-EMR residual lesions associated with severe fibrosis. Perforation occurred in 11.6% and resulted in emergency surgery and incomplete resection in 1 (2.3%) and 2 (4.6%) of cases.

Disclosure of Interest: None declared

P1055 DIFFERENTIAL CHARACTERISTICS OF COLORECTAL CANCER FOLLOWING THE SERRATED PATHWAY

Ó. Murcia¹, M. Rodríguez¹, M. Juárez¹, E. Hernández-Illán¹, C. Alenda¹, A. Payá¹, L. Castaño¹, R. Jover¹

¹Unidad de Gastroenterología, Hospital General Universitario de Alicante, Alicante, Spain

Contact E-mail Address: omp_89@hotmail.com

Introduction: Recently, it has been described a new colorectal cancer (CRC) carcinogenetic pathway due to methylation of CpG islands (methylator phenotype or CIMP). There’s some controversy about its prognostic and response to adjuvant Chemotherapy (CT).

Aims & Methods: The aim of this study is to determine differential characteristics of CIMP CRC and to evaluate its prognostic and response to CT. There were been included 701 CRC patients consecutively from the national and multicentre Epicolon II project. Hypermethylation of CpG islands was studied by MS-MLPA method using RUN-X3, CACNA1G, IGF2, MLH1, NEUROG1, CRABP1, SOCS1 and CDKN2A markers in 614 patients, taking into account for CIMP+ the methylation of 5 or more of these markers.

Results: The median of age was 72 years old [34-93], being men 58.9%. The median of follow-up was 57.7 months. It was produced a recurrence in 146 patients (20.8%) and 278 (39.7%) were deceased at the end of the follow-up period (82.7 months). The study of methylator phenotype was possible to value in 543 patients (77.5%), distributed in 146 CIMP+ (26.9%) and 397 CIMP- (73.1%) patients. Some features between CIMP+ and CIMP- CRCs were compared. The age of the firsts at diagnosis was higher (CIMP+ 72.8 [39-93]; CIMP- 70.8 [34-93]; p < 0.043) and some trend to be located at right colon was observed (CIMP+ 55.6%; CIMP-26.6%; p < 0.001). It was also found a higher KRAS mutations proportion in CIMP+ (43.7% CIMP+; 31.7% CIMP-; p < 0.013), as well as in BRAF genes (14.9% CIMP+; 0.8% CIMP-; p < 0.001) and DNA mismatch repair genes alterations (24.3% CIMP+; 5.6% CIMP-; p < 0.001), without any difference in sex field. In addition, there weren’t observed any difference neither survival nor recurrence between overall CIMP+ and CIMP-. However, when we stratified by genetic profile, we observed a higher survival in CIMP+ CRC with KRAS mutation (log Rank p < 0.023) conversely to those with KRAS mutation but CIMP- (log Rank p < 0.759). It was also observed a higher intrinsic survival in microsatellite instability (MSI) and CIMP- CRCs (log Rank p < 0.032) than those MSI and CIMP+ CRCs (log Rank p < 0.384). By receiving CT with curative purpose (II with poor prognosis and III stages), some differences were found between CIMP+ and CIMP- CRCs. Patients with CIMP- CRC obtained benefits in disease-free survival terms (log Rank p < 0.001), something that didn’t occur in patients with CIMP+ CRC (log Rank p < 0.180). Moreover, after stratifying by genetic profile, those microsatellite stable (MSS) and CIMP- CRCs were benefiting from receive CT in disease-free survival terms (log Rank p < 0.001), situation that didn’t happened in MSS and CIMP+ CRCs (log Rank p < 0.164).

Conclusion: There are observed certain differential features in methylator phenotype CRC. Overall, those patients present a worse response to adjuvant CT with curative purpose.

Disclosure of Interest: None declared

P1056 THE TOP 100 INFLUENTIAL MANUSCRIPTS IN COLORECTAL CANCER: A BIBLIOMETRIC ANALYSIS

P. F. Wrafter¹, T. M. Connelly², J. Khan³, L. Devane⁴, W. P. Joyce¹

¹Surgery, Galway Clinic, ²Surgery, University Hospital Galway, Galway, ³Surgery, Beaumont Hospital, ⁴Surgery, St Vincents University Hospital, Dublin, Ireland

Contact E-mail Address: p.wrafter1@gmail.com

Introduction: Colorectal cancer (CRC) is a significant cause of mortality and morbidity worldwide. There is a large and growing body of evidence on the topic. Recently bibliometric citation analysis has been used to determine the most influential scientific papers in several surgical fields. To date, no study has been undertaken to determine the most influential papers in the field of CRC.

Aims & Methods: To analyse the 100 most cited manuscripts in the field of CRC to highlight the key topics and studies which have led to the current understanding and treatment of the disease.

A search of the Thomson Reuters Web of Science citation indexing database was completed using the search terms ‘colorectal cancer,’ ‘colon cancer,’ ‘rectal cancer,’ ‘colorectal carcinoma,’ ‘colon carcinoma,' ‘rectal carcinoma' or ‘colonoscopy.’ Only English language and full manuscripts were included. The 100 most cited papers were further analysed by topic, journal, author, year and institution

Results: 146,833 eligible papers were returned. Of the top 100, the most cited paper (by Hurwitz) focused on chemotherapy (5340 citations). The New England Journal of Medicine published the highest number of papers in the top 100 (n=24, 37,858 citations). The country and year with the greatest number of publications were the USA (n=60) and 2004 (n=13) respectively. The most covered topic was genetics in CRC (n=51), followed by chemotherapy (n=21) and surgical management (n=6).

Conclusion: These most cited manuscripts have contributed to the current understanding and treatment of CRC. We provide an analysis and reference of what could be considered the most influential papers in CRC

Disclosure of Interest: None declared

P1057 OUTCOME OF SELF-EXPANDABLE METALLIC STENT( SEMS) PLACEMENTS FOR COLORECTAL OBSTRUCTION AND EXPERIENCE WITH COLONOSCOPY THROUGH A COLORECTAL STENT

I. A. Kawana¹, R. Kyo¹

¹Gastroenterology, Saiseikai Yokohamashi Nanbu Hospital, Yokohama, Japan

Contact E-mail Address: ich.kawana@gmail.com

Introduction: In January 2012, endoscopic stenting with a self-expandable metallic stent(SEMS) for malignant colonic obstruction was covered by the national health insurance in Japan. And this procedure is widely accepted in Japan.

In our institution, this procedure was performed aggressively for the cases of symptomatic malignant colorectal obstruction.

Aims & Methods: The aim of this study is to research the safety and feasibility of SEMS placement as a bridge to surgery (BTS) for malignant colorectal obstruction, and showed the utility of total colonoscopy (TCS) pass through a SEMS.

From July 2012 to July 2014, a prospective study was performed on 29 patients with malignant colorectal obstruction who treated with SEMS. Only colon cancer patients who underwent BTS SEMS placement were selected. After SEMS placement,11 patients was performed a TCS pass through a SEMS.

Results: In total, 20 patients were included. The median age 68 years (43-89 years), sex ratio 10:10, stenting sites transverse colon 3 cases, descending colon 3 cases, sigmoid colon 7 cases, rectum seven cases. The median time from diagnosis to stenting was one day, the average treatment time 29 minutes, procedural success rates was 100%, and a clinical success rates was 95%. Procedure related contingent disease has not been observed, perforation was observed in one case after placement of SEMS. The median time of the start meal after SEMS placement was two days. The median time from SEMS insertion to surgery was 21.5 days. Open surgery was performed in 16 cases and laparoscopic colectomy was performed in 4 cases. The overall stoma creation was 2 cases (perforated case and intestinal necrosis case).

In 11 cases, TCS after stenting was carried out under CO2 air, and under fluoroscopic guidance. The median time from stenting to TCS was 12 days. Average time to cecum reached was 20 minutes. Complications associated with TCS were not observed. The eight of the eleven cases were observed other lesions such as adenoma and cancer. In four cases, cancer was observed in deep colon than stent. EMR was performed in one case of adenoma, complications were not observed. EMR is performed in one cases of adenoma, complications were not observed.

Conclusion: Stenting for the BTS is safe and effective. Furthermore, TCS pass through a SEMS after SEMS placement was very useful for diagnosis. It becomes possible to evaluate the deep large intestine than stent. The incidence of concurrent colorectal cancer was reported around 8%. TCS pass through the SEMS can be possible to correct preoperative diagnosis, it is considered to be useful in the selection of the surgical procedure.

Disclosure of Interest: None declared

P1058 PROOF-OF-PRINCIPLE FOR A NOVEL GAS-SENSING CAPSULE AS AN IN VIVO MARKER FOR INTESTINAL GAS PRODUCTION

C. Yao¹, N. Ha², J. Z. Ou², N. Pillai², M. L. Cox³, J. J. Cottrell³, J. G. Muir¹, F. R. Dunshea³, P. R. Gibson¹, K. Kalantar-Zadeh²

¹Department of Gastroenterology, Alfred Centre, Monash University, ²School of Electrical and Computer Engineering, RMIT University, Melbourne, ³Department of Agriculture and Food Systems, The University of Melbourne, Parkville, Australia

Contact E-mail Address: chu.yao@monash.edu

Introduction: The production of intestinal gases are closely linked with the genesis of gastrointestinal symptoms. However, direct measurements of these gases in vivo are limited and have involved invasive or indirect (e.g., via breath) sampling techniques (1). A novel gas-sensing capsule was recently developed to detect concentrations of specific gases in real time within the gastrointestinal tract (1).

Aims & Methods: The aim of this preliminary study was to validate the use of gas sensor capsule in an animal model following diets varying in readily fermentable carbohydrate content. Six pigs were randomised to 30 MJ diets containing either low (7 g resistant starch (RS) & 0 g oligosaccharides) or high (29 g RS & 31g oligosaccharides) fermentable carbohydrates for 4 days after 1-week of acclimatisation to human-type diets. On the second day of each diet, carbon dioxide (CO₂)-sensing capsules were administered via gavage and data transmitted every 5 minutes to an external receiver. The readout represents relative CO₂ concentration (ppm) sampled at a specific timepoint. Passage rate of the capsules were also determined.

Results: In pigs receiving a high-fibre diet, all 3 gas capsules were passed within 10 days of administration whilst only 1 of 3 capsules were passed within this time period in those on a low-fibre diet. 2 capsules failed (one did not empty from the stomach, one transmission failure). 4 devices successfully transmitted data on CO₂ production for 8-24 hoursand results are shown in the Table. In the first 8 hours when the capsule is in the stomach and small intestine, mean CO₂ concentrations were 53 x 10³ ppm with no clear differences between diets. The 2 capsules with long duration of transmission showed a divergence of CO₂ concentrations from 10 to 16 hours. This divergence of CO2 concentrations probably represents exhaustion of fermentable substrates of carbohydrates in the proximal colon, consistent with the anticipated site of such fermentation. The convergence of CO₂ production after 16 hours is consistent with fermentation of endogenous or of less readily fermented carbohydrates common to both diets.

Table.

Capsule sensor results. FC=fermentable carbohydrate, X =no data transmission

Capsule sensor ID	Mean CO2 concentrations (x 103 ppm) at 2-hour intervals
0 h	8 h	10 h	12 h	14 h	16 h	18 h	20 h	22 h	24 h
Sensor 1 (Low FC)	0	55	X	X	X	X	X	X	X	X
Sensor 2 (High FC)	0	68	X	X	X	X	X	X	X	X
Sensor 3 (Low FC)	0	46	46	46	33	33	56	64	64	62
Sensor 4 (High FC)	0	41	51	54	51	54	54	54	59	X

Conclusion: We have provided a proof-of-principle for the utility of a gas-sensing capsule for measuring gas concentrations within the gastrointestinal tract with demonstration of the anticipated differences associated with variations of fermentation patterns. Further work on refining the reliability of the capsule’s transmission mechanism and in identifying sites of gas measurement are needed to become a valuable, non-invasive marker of intestinal gas production.

Disclosure of Interest: None declared

P1059 MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 4 REGULATES LINACLOTIDE-INDUCED CYCLIC GMP AND ELECTROLYTE SECRETION

B. Tchernychev¹, P. Ge¹, D. Wachtel¹, R. Solinga¹, M. Kessler¹, S. Ranganath¹, G. Hannig¹, I. Silos-Santiago¹

¹Ironwood Pharmaceuticals, Inc., Cambridge, United States

Introduction: Multidrug resistance-associated protein 4 (MRP4) is an ATP-binding cassette transporter that mediates the efflux of prostaglandins and cyclic nucleotides (cAMP and cGMP). MRP4 acts as an important regulator of these secondary messengers and thereby affects signalling events mediated by cAMP and cGMP. MRP4 is expressed on intestinal epithelial cells and has recently been found to be downregulated in patients with irritable bowel syndrome with constipation (IBS-C). Moreover, intestinal MRP4 has been implicated in the compartmentalised regulation of cAMP-mediated signalling.¹ Linaclotide, a potent and selective guanylate cyclase-C (GC-C) agonist, is approved for the treatment of IBS-C in the United States and Europe and in the United States at a lower dose for the treatment of chronic idiopathic constipation. GC-C activation by linaclotide results in increased cGMP synthesis; however, the role of intestinal MRP4 in regulating the levels of intracellular cGMP has not been studied.

Aims & Methods: The objective of this study was to evaluate the role of MRP4 in the regulation of cGMP levels in linaclotide-stimulated rat colonic epithelium and to simultaneously assess the effect of MRP4 inhibition on GC–C–mediated transepithelial ion (Isc) current. Ussing chamber assays were used to study the role of MRP4 on linaclotide-induced secretion of electrolytes and cGMP. The kinetics of the deactivation of linaclotide-induced Isc was studied using a GC-C/Fc fusion protein. MRP4 expression was assessed by Q-PCR and immunohistochemistry.

Results: Staining of rat colonic epithelium with anti-MRP4 antibodies showed expression of MPR4 in the apical membrane. Stimulation with linaclotide resulted in the accumulation of intracellular cGMP and induced Isc in isolated intestinal epithelium. Pretreatment of mucosa with the specific MRP4 inhibitor MK571 potentiated linaclotide-induced electrolyte secretion and augmented intracellular cGMP accumulation. Additionally, pretreatment of colonic mucosa with the phosphodiesterase type 5 inhibitor sildenafil increased basal Isc but had no amplifying effect on linaclotide-induced ion current. Inhibition of MRP4 only affected the activation, not the deactivation, phase of linaclotide-induced Isc, an effect elicited by the GC-C/Fc chimera. Stimulation with linaclotide induced cGMP secretion from both apical and basolateral membranes of the colonic epithelium. However, MK571 inhibited cGMP efflux from the apical but not from the basolateral membranes.

Conclusion: MRP4 is highly expressed on the apical membrane of rat colonocytes, and apical MRP4 mediates cGMP efflux from linaclotide-stimulated colonic epithelium. MK571 inhibition of cGMP efflux increases Isc induced by linaclotide. The selective inhibition of apical cGMP secretion by MK571 suggests the involvement of transporters other than MRP4 for basolateral cGMP secretion. A potential role of MRP4 in IBS-C is under investigation.

Disclosure of Interest: B. Tchernychev Financial support for research: Ironwood Pharmaceuticals/Actavis, Conflict with: Employee of Ironwood Pharmaceuticals, P. Ge Conflict with: Employee of Ironwood Pharmaceuticals, D. Wachtel Conflict with: Employee of Ironwood Pharmaceuticals, R. Solinga Shareholder: Ironwood Pharmaceuticals, Conflict with: Employee of Ironwood Pharmaceuticals, M. Kessler Conflict with: Employee of Ironwood Pharmaceuticals, S. Ranganath Shareholder: Enumeral Biomedical Corporation, Conflict with: Employee of Enumeral Biomedical Corporation, Former employee of Ironwood Pharmaceuticals, G. Hannig Shareholder: Ironwood Pharmaceuticals, Conflict with: Employee of Ironwood Pharmaceuticals, I. Silos-Santiago Shareholder: Ironwood Pharmaceuticals, Conflict with: Employee of Ironwood Pharmaceuticals

P1060 LINACLOTIDE INDUCES SECRETION OF CYCLIC GMP INTO THE COLONIC SUBMUCOSAL LAYER: AN IN VIVO MICRODIALYSIS STUDY IN RATS

J. Tobin¹, S. Thomas², R. Solinga¹, J. Masferrer¹, C. Lunte², G. Hannig¹, I. Silos-Santiago¹

¹Ironwood Pharmaceuticals, Inc., Cambridge, ²University of Kansas, Lawrence, United States

Introduction: Linaclotide, a guanylate cyclase-C (GC-C) agonist, is currently approved for irritable bowel syndrome with constipation (IBS-C) in the United States and Europe and in the United States at a lower dose for the treatment of chronic idiopathic constipation. The effects of linaclotide on intestinal transit and secretion are mediated through cyclic guanosine monophosphate (cGMP) production. In addition, cGMP mediates the effect of linaclotide on visceral pain, and it has been hypothesised that this effect is through the direct inhibition of nociceptors found in the colonic submucosa. However, the levels of cGMP in the colonic submucosa after GC-C activation have not yet been measured.

Aims & Methods: The objective of this study was to assess the release of cGMP in the rat colonic submucosa after linaclotide administration using in vivo microdialysis. Microdialysis probes were implanted in the submucosa of the ascending colon of anaesthetised rats. Linaclotide (3 doses: 0.5, 1.7 and 5 μg) or 200 μL vehicle alone were injected directly into the lumen of the colonic loop (n=4–10/group). cGMP concentrations in the dialysate were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). At the end of the study, loops were excised, and length and weight were measured. The change in cGMP concentrations before and after treatment was compared with vehicle group using a two-tailed paired student’s t-test. The fluid secretion change after treatment was compared with vehicle group using one-way ANOVA followed by a Dunnett's post hoc test.

Results: Linaclotide administered into rat colonic loops resulted in a significant increase in fluid secretion compared with vehicle alone for all doses tested (175–198%; P≤0.001). In dialysate samples, doses of 0.5, 1.7 and 5 μg linaclotide increased cGMP release into the submucosal layer in a dose-dependent manner by 58%, 73% and 212%, respectively, compared with vehicle control. For all doses of linaclotide, significant increases in cGMP concentration were observed compared with vehicle. Additionally, the changes in cGMP release were time dependent, with the highest dose reaching maximal effect within 12 minutes of linaclotide administration.

Conclusion: Linaclotide induces fluid secretion in the colonic lumen and increases cGMP levels in the colonic submucosa. The release of cGMP into the rat colonic submucosa further supports the mechanism of action of linaclotide on intestinal visceral pain.

Disclosure of Interest: J. Tobin Financial support for research: Ironwood/Actavis, Shareholder: Ironwood Pharmaceuticals, Conflict with: Employee of Ironwood Pharmaceuticals, S. Thomas: None declared, R. Solinga Shareholder: Ironwood Pharmaceuticals, Conflict with: Employee of Ironwood Pharmaceuticals, J. Masferrer Conflict with: Employee of Ironwood Pharmaceuticals, C. Lunte: None declared, G. Hannig Shareholder: Ironwood Pharmaceuticals, Conflict with: Employee of Ironwood Pharmaceuticals, I. Silos-Santiago Shareholder: Ironwood Pharmaceuticals, Conflict with: Employee of Ironwood Pharmaceuticals

P1061 ROLE OF NA+/CA2+ EXCHANGER 1 AND 2 ON THE CONTRACTILITY IN LONGITUDINAL MUSCLES OF MOUSE ILEUM

K. Nishiyama¹, Y.-T. Azuma¹, S. Kita², H. Nakajima¹, T. Iwamoto², T. Takeuchi¹

¹Osaka Prefecture University, Izumisano, ²Fukuoka University, Fukuoka, Japan

Contact E-mail Address: dy203008@edu.osakafu-u.ac.jp

Introduction: Increase in intracellular Ca²⁺ concentration are crucial to the regulation of smooth muscle contraction. Ca²⁺ clearance requires Ca²⁺ transport out of the cytosol by pathways involving plasma membrane Ca²⁺-ATPase, the Na⁺/Ca²⁺ exchanger (NCX), the sarco/endoplasmic reticulum Ca²⁺-ATPase, and mitochondria. NCX electrogenically exchanges Na⁺ and Ca²⁺ across the plasma membrane depending on the membrane potential and transmembrane gradients. The physiological roles by which NCX influences gastrointestinal motility are incompletely understood, although its role in heart, brain and kidney is understood.

Aims & Methods: In this study, we focused on the effect of Ca²⁺ movement through NCX on the motility in ileum because Ca²⁺ homeostasis is central to the regulation of smooth muscle function. To determine the role of NCX1 and NCX2 in the ileum, we investigated the frequency–responses to electric field stimulation (EFS) at 1 and 3 Hz in the longitudinal muscle obtained from the ileum in wild-type mice (WT), NCX1-heterozygote knockout mice (NCX1 HET), and NCX2-heterozygote knockout mice (NCX2 HET).

Results: In the ileum, EFS induced a phasic contraction that persisted during the stimulus, and a tonic contraction that recorded after the end of the stimulus. Under the condition of EFS at 1 Hz, we found that the amplitudes of phasic contraction were significantly smaller in NCX2 HET, but not NCX1 HET, than in WT. Like phasic contraction, the amplitudes of tonic contraction were significantly smaller in NCX2 HET, but not NCX1 HET, than in WT. Under the condition of EFS at 3 Hz, the amplitudes of tonic contraction were significantly smaller in NCX2 HET, but not NCX1 HET, than in WT. However, the amplitudes of phasic contraction were same among WT, NCX1 HET, and NCX2 HET, unlike 1 Hz. Next, we determined whether NCX deficiency affects contraction in response to acetylcholine (ACh) and substaqnce P (SP) in smooth muscle cells. NCX2 HET, but not NCX1 HET, demonstrated that magnitude of ACh-induced and SP-induced contractions was smaller than that of WT.

Conclusion: In this study, we demonstrated that NCX2 regulated the motility in ileum through by controlling the sensitivity of ileal smooth muscles to ACh and SP.

Disclosure of Interest: None declared

P1062 ROLES OF NA+ / CA2+ EXCHANGER 1 AND 2 IN MOUSE DIARRHEA MODEL

K. Tanioka¹, Y.-T. Azuma¹, S. Kita², H. Nakajima¹, T. Iwamoto², T. Takeuchi¹

¹Osaka Prefecture University, Izumisano, ²Fukuoka University, Fukuoka, Japan

Contact E-mail Address: su205023@edu.osakafu-u.ac.jp

Introduction: The Na+/Ca²+ exchanger (NCX) is a plasma membrane transporter involved in regulating intracellular Ca²+ concentrations. NCX is critical for Ca²+ regulation in cardiac muscle, vascular smooth muscle, and nerve fibers. However, little is known about the physiological role of NCX in the gastrointestinal tract. Using in vitro magnus method, we have previously demonstrated that NCX2, but not NCX1, regulates colonic motility by altering acetylcholine release onto myenteric neurons of the distal colon. Alterations in colonic motility relates to the cause of diarrhea as one proposed mechanism.

Aims & Methods: The aim of this study was to characterize the role of NCX1 and NCX2 on gastrointestinal motility in vivo in normal conditions and diarrhea models. Both NCX1 heterozygous mice (HET) and NCX2 HET on the C57BL/6 background were comparable in all analyses to age-matched wild-type mice (WT). Diarrhea was induced by oral administration of MgSO₄ (2 g/kg), i.p. administration of serotonin (3 mg/kg) or prostaglandin E₂ (0.1 mg/kg). The stool output was assessed in each mouse. The number and weight of stool was counted over 9 hour for MgSO₄, or 60 min for serotonin and prostaglandin E₂. Stools were graded into three consistency levels as follows: normal, soft, watery.

Results: In MgSO₄-induced diarrhea, almost all mouse exhibited watery diarrhea. We found that the number and weight of watery stool in NCX1 HET were clearly greater than those in WT over a period of 5-6 hour. Similarly, the number and weight of watery stool in NCX2 HET were markedly greater than those in over a period 3-4 hour. In serotonin-induced diarrhea, the number and weight of watery stool in NCX2 HET were greater than those in WT over periods 0-15 min and 15-30 min. NCX1 HET displayed no changes of the number and weight of watery stool, unlike MgSO₄-induced diarrhea. In prostaglandin E₂-induced diarrhea, it showed no significant alteration in number and weight of watery stool among WT, NCX1 HET, and NCX2 HET.

Conclusion: We demonstrated for the first time using mouse diarrhea model that NCX1 and NCX2 have important roles in the development of diarrhea.

Disclosure of Interest: None declared

P1063 ROLE OF TRANSIENT RECEPTOR POTENTIAL C6 CHANNEL ON THE CONTRACTILITY IN CIRCULAR MUSCLES OF MICE ILEUM

S. Suzuki¹, Y-T. Azuma¹, S. Kita², H. Nakajima¹, T. Iwamoto², T. Takeuchi¹

¹Veterinary Pharmacology, Osaka Prefecture University, Izumisano, ²Fukuoka University, Fukuoka, Japan

Contact E-mail Address: su205019@edu.osakafu-u.ac.jp

Introduction: Transient receptor potential cation (TRPC) channels are a group of ion channels, which are relatively non-selectively permeable to cations. TRPC channels are activated in downstream of Gq/11-coupled receptors, or receptor tyrosine kinases. There is no direct evidence for role of functional TRPC6 on gastrointestinal tract. Acetylcholine and substance P have been reported to be the representative neurotransmitters that cause contractions in the gastrointestinal tracts of nearly all animal species including human being. There neurotransmitters activate muscarinic and tachykinin receptor, respectively, that belong to G protein-coupled receptor.

Aims & Methods: The aim of the present study was to investigate the role of TRPC6 in gastrointestinal motility. Both smooth muscle-specific TRPC6 transgenic mice (Tg), and smooth muscle-specific dominant-negative TRPC6 transgenic mice (DN) on the C57BL/6 background were comparable in all analyses to age-matched wild-type mice (WT). We used an organ tissue bath system to investigate the motility of circular smooth muscle segments isolated from the ileum.

Results: In the ileum, electric field stimulation (EFS; 60 sec)-induced contraction was showed during the stimulus. The amplitudes of EFS-induced contraction were significantly greater in Tg than in WT, and significantly smaller in DN than in WT. In the experiment in which atropine was added, the first phase of EFS (∼15 sec)-induced contraction was completely inhibited in all of three types. Interestingly, second phase of EFS (15∼60 sec)-induced contraction were still greater in Tg than in WT, and still smaller in DN than in WT. We next tested the NK1 or NK2 receptor antagonist in addition to atropine. Importantly, NK2 antagonist, but not NK1 antagonist, markedly suppressed the increased contraction in Tg. In DN, both NK1 and NK2 antagonist inhibited the contraction.

Conclusion: In this study, we demonstrated that TRPC6 has physiological roles in the contractility of the ileum and that TRPC6 channels activated by muscarinic and NK receptors to regulate the motility. In case of overexpression of TRPC6 channels, furthermore, our results suggest that relation of TRPC6 with NK2 receptor may alter and affect the motility.

Disclosure of Interest: None declared

P1064 DIFFERENCES ON TIME TO PEAK OF CARBACHOL-INDUCED CONTRACTION IN BETWEEN CIRCULAR AND LONGITUDINAL SMOOTH MUSCLES OF MOUSE ILEUM

T. Takeuchi¹, N. Samezawa¹, Y.-T. Azuma¹

¹Osaka Prefecture University, Izumisano, Japan

Contact E-mail Address: takeuchi@vet.osakafu-u.ac.jp

Introduction: Cooperation between contractions on the oral side of contents and relaxation on the anal side in digestive tract is physiologically important for peristaltic movement. The muscular layer in gastrointestinal tract consists of an inner circular muscular layer and an outer longitudinal muscular layer. These muscular layers are responsible for the movement such as peristalsis. Acetylcholine (ACh) has been reported to be the representative neurotransmitter that causes contractions in the gastrointestinal tracts of nearly all animal species. Although there are many reports about contractions of longitudinal smooth muscles induced by activation of muscarinic receptor (MR), little is known about the details of those of the circular smooth muscles. Thus, a detailed investigation of the ACh-induced contraction of circular smooth muscle is needed to provide insight into the regulatory mechanisms of gastrointestinal motility.

Aims & Methods: The aim of the present study was to investigate detailed contractile response in the circular smooth muscles of the mouse ileum. To compare detailed contraction response in the circular and longitudinal smooth muscles, we used circular and longitudinal small muscle strips (0.2 mm × 1 mm) of the mouse ileum. The time from carbamylcholine (CCh) treatment to peak of contraction, and the amplitudes of contractions were compared between circular and longitudinal muscle small strips.

Results: The time to peak phasic contractile responses to CCh was significantly 5 minutes longer in the small muscle strips of circular muscle (5.7 min) than in those of longitudinal muscle (0.4 min). The amplitudes of contractions in the small muscle strips of circular muscle were similar in that of longitudinal muscle. Tetrodotoxin and N^ω-nitro-L-arginine had no effect on CCh-induced contractions of circular muscle. Regarding contraction, the pD₂ values for CCh were 0.86 ± 0.05 mM for circular muscle and 0.82 ± 0.07 mM for longitudinal muscle. The selective M2R antagonist methoctramine (100 nM) had no effect on CCh-induced contraction in circular and longitudinal muscle small strips. In contrast, the selective M3R antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (10 nM) completely suppressed CCh-induced contractions in both circular and longitudinal muscle small strips. Furthermore, Ca²⁺ channel blocker nicardipine (10 nM) markedly suppressed CCh-induced contractions on the circular and longitudinal muscles.

Conclusion: In this study, we demonstrate that the time to peak, which means the time from M3R activation to contraction, was slower in circular smooth muscles than in longitudinal smooth muscles.

Disclosure of Interest: None declared

P1065 ANORECTAL HIGH DEFINITION MANOMETRY: A COMPARISON BETWEEN HEALTHY VOLUNTEERS, FECAL INCONTINENCE AND FUNCTIONAL CONSTIPATION

A. Garros¹, A. Ropert², M. Bouvier³, H. Damon¹, C. Brochard², V. Vitton³, L. Siproudhis², S. Roman¹, F. Mion¹

¹Exploration fonctionnelle digestive - Hopital Edouard Herriot, LYON, ²Hépato-Gastro-Entérologie - Hopital Pontchaillou, RENNES, ³Gastroentérologie - Hôpital Nord, MARSEILLE, France

Contact E-mail Address: aurelien.garros@chu-lyon.fr

Introduction: Anorectal high-definition manometry (high resolution with 3D, ARHDM) allows a precise definition of pressure profile. However normal values are scarce with this device. Our aim was to determine normal values and manometric profiles in fecal incontinence (FI) and functional constipation (FC) patients in a prospective multicenter trial (NCT01710579).

Aims & Methods: One hundred and twenty seven subjects were included in 3 centers. We are presenting results for 33 healthy volunteers (HV, 25 women, mean age 48 years), 33 FI patients (33 women, mean age 58) defined by Vaizey score > 6 and constipation Kess score < 9 and 37 FC patients (35 women, mean age 53) defined by Kess score > 9 and Vaizey score < 6 . All subjects underwent endoanal ultrasound examination to detect anal sphincter defects. ARHDM was performed using a rigid probe (Given Imaging, Duluth, GA). The protocol consisted of a 2-minute resting period, 2 squeezing periods (>30 seconds) and 2 push maneuvers. The high-pressure zone (HPZ) corresponding to the anal canal was delineated at the 20-mmHg isobaric contour. The height and mean pressure of the HPZ were measured over a 20-s period at the end of the resting period and after the beginning of each squeezing period, and over a 5-s period s after the beginning of each push period. Because rectal pressure cannot be adequately assessed with this probe, we chose the ratio [push/rest] of the mean pressures of the anal HPZ to quantify the push maneuvers (anal relaxation was considered as present if this ratio was <0.8). Data are expressed in median (IQR) and compared between groups using non-parametric tests.

Results: FI patients were significantly older (p < 0.05 vs the other groups). Anal resting manometric parameters were significantly different between HV and FI (Table). Anal squeezing manometric parameters were significantly different between the 3 groups. In healthy females, anal pressures were similar in those with (4 subjects) and without anal sphincter defect. In FI women, resting, but not squeezing, anal pressures were significantly lower when an anal sphincter defect was present (16 patients, 49%). Increased anal pressure or absence of anal relaxation during push maneuvers was observed in the majority of HV and patients.

Abstract number: P1065

Manometric data		Volunteers	Incontinence	Constipation
Rest	HPZ pressure (mmHg) *	50 (42-55)	42 (34-47) †	47 (40-62) ‡
HPZ height (cm) *	3.5 (3.0-4.0)	3.0 (2.5-3.8) †	3.3 (2.4-4.1)
Squeeze	HPZ pressure (mmHg) *	81 (68-106)	56 (45-69) †	64 (54-96) † ‡
HPZ height (cm) *	4.5 (4.2-4.9)	4.1 (3.4-4.6) †	4.4 (4.0-4.9) ‡
Push	Ratio [push/rest] mean pressure *	0.98 (0.81-1.21)	0.98 (0.89-1.14)	1.02 (0.82-1.26)
% of patients withratio > 0.8	19 (79%)	20 (71%)	21 (75%)

*median (IQR)

† p < 0.05 (compared to volunteers)

‡ p < 0.05 (compared to incontinence)

Conclusion: This study established normal values for ARHDM, and showed differences between controls, patients with FI and patients with FC for resting and squeezing anal pressures, as well as for HPZ height. More than 70% of HV and patients had no significant anal pressure decrease during push: rectoanal dyssynergia must be assessed differently using this new technology.

Disclosure of Interest: A. GARROS: None declared, A. ROPERT: None declared, M. BOUVIER: None declared, H. DAMON Consultancy: Medtronic/Covidien, C. BROCHARD: None declared, V. VITTON: None declared, L. SIPROUDHIS: None declared, S. ROMAN Financial support for research: Given Imaging/Covidien/Medtronic, Consultancy: Given Imaging/Covidien/Medtronic, F. MION Financial support for research: Given Imaging/Covidien/Medtronic, Consultancy: Given Imaging/Covidien/Medtronic.

P1066 PERCUTANEOUS ENDOSCOPIC CAECOSTOMY: FEASIBILITY, EFFICACY AND COMPLICATION RATES IN REFRACTORY COLORECTAL DISORDERS

J. Ricard¹, M. Le Rhun², E. Chabrun¹, E. Duchalais², S. Bruley des Varannes², F. Zerbib¹, E. Coron²³

¹Department of Gastroenterology and Hepatology, University Hospital Saint Andre, Bordeaux, ²Digestive Diseases Institute, ³INSERM U913, University Hospital Hotel Dieu, Nantes, France

Contact E-mail Address: emmanuel.coron@gmail.com

Introduction: Percutaneous endoscopic caecostomy (PEC) has been proposed as an alternative to the Malone intervention with promising results to perform antegrade colonic enemas (ACE). However, the small number of patients and short-term follow up require further assessment of PEC. Therefore, the goal of this prospective study was to assess the feasibility and efficacy of PEC in a multicenter study and a larger group of patients.

Aims & Methods: The study was conducted in 2 centers between September 2006 and April 2014. The PEC procedure was standardized between the centers and was performed under general anesthesia during a colonoscopy. It consisted in 1) puncturing the caecum after endoscopic transillumination to introduce the Chait™ catheter (Cook, USA) and 2) creating a caecopexy with 3-4 anchors. The indications of PEC were constipation, fecal incontinence and incontinence after rectal resection, refractory to medical treatment. For each indication the primary endpoint was improvement of quality of life score (GIQLI). GIQLI score, constipation score (Kess), incontinence score (Cleveland) were calculated before the PEC and at 3, 6, 12 and 24 months. The overall success of PEC procedure was defined by improvement quality of life, the absence of removal of the device, of colectomy or colostomy.

Results: A total of 69 patients were included, 67 with follow-up > 3 months (2 were lost to follow-up). Constipation, fecal incontinence and rectal resection groups comprised 43, 19 and 10 patients. Mean follow-up was 2 years in the first two groups and 6 months in the third group. GIQLI scores were significantly improved in constipation group (p = 0.034), incontinence group (p = 0.026) and rectal resection group (p = 0.013). In the constipation group, Kess scores were 25.9 before ACE and 20.6 at 2 years (p < 0.05 = 0.012). In the incontinence group, mean Cleveland scores were 14.9 before ACE and 10.4 at 2 years (p = 0.045). In the rectal resection group, the scores went from 14.3 to 2.7 at 6 months (p = 0.014). Overall, success percentages in the constipation group, incontinence group and rectal resection group were 58.1% (25/43), 73.7% (14/19) and 90.0% (9/10), respectively. Complications rates were as follows: prolonged pain on the catheter site (50.7%), local bud (41.8%), catheter suspected infection in 13 cases (19.4%). 19 devices (28.4%) were withdrawn because of functional failure or complication.

Conclusion: Percutaneous endoscopic caecostomy for antegrade colonic enemas allows obtaining a significant improvement in the quality of life in patients with colorectal disorders refractory to medical treatment. Persistent pain at the catheter site, which was the most frequent complication in our study, suggests that adaptative measures of the PEC technique are needed in order to provide optimal patient’s care.

Disclosure of Interest: J. Ricard: None declared, M. Le Rhun: None declared, E. Chabrun: None declared, E. Duchalais: None declared, S. Bruley des Varannes: None declared, F. Zerbib: None declared, E. Coron Financial support for research: Cook Medical, Lecture fee(s): Cook Medical

P1067 EFFICACY AND SAFETY OF PRUCALOPRIDE IN ADULTS WITH CHRONIC CONSTIPATION: AN INTEGRATED ANALYSIS OF SIX RANDOMIZED CONTROLLED CLINICAL TRIALS

H. Piessevaux¹, M. Camilleri², Y. Yiannakou³, J. Tack⁴, E. M. Quigley⁵, M. Ke⁶, S. Da Silva⁷, A. Levine⁸, R. Kerstens⁹

¹Cliniques Universitaires Saint-Luc, Brussels, Belgium, ²College of Medicine, Mayo Clinic, Rochester, MN, United States, ³County Durham and Darlington NHS Foundation Trust, Durham, United Kingdom, ⁴Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium, ⁵Houston Methodist Hospital, Houston, TX, United States, ⁶Peking Union Medical College Hospital, Chinese Academy of Medical Science, Bejing, China, ⁷Shire, Brussels, Belgium, ⁸Shire, Wayne, PA, United States, ⁹Orion Statistical Consulting BV, Hilvarenbeek, Netherlands

Contact E-mail Address: hubert.piessevaux@uclouvain.be

Introduction: Prucalopride, a selective, high-affinity serotonin receptor 4 agonist, stimulates gastrointestinal motility and alleviates common symptoms of constipation in adults.

Aims & Methods: The aim of this study was to perform an integrated analysis of the efficacy and safety of prucalopride 2 mg daily in men and women. Data were combined from six phase 3 and 4, international, multicentre, double-blind, randomized, placebo-controlled, parallel-group trials with similar study designs and endpoints. The primary efficacy endpoint was the proportion of patients with a mean frequency of ≥ 3 spontaneous complete bowel movements (SCBMs) per week over 12 weeks of treatment. Several secondary efficacy endpoints were assessed (at baseline and at the final on-treatment assessment) using patient diaries and the validated Patient Assessment of Constipation – Symptoms (PAC-SYM) and Patient Assessment of Constipation – Quality of Life (PAC-QOL) questionnaires. Safety was assessed throughout the studies.

Results: Overall, 2484 patients were included in the integrated efficacy analysis (1237 received prucalopride and 1247 received placebo) and 2552 patients (prucalopride: 1273, placebo: 1279) were included in the integrated safety analysis. Most patients were women (78.3%) and Caucasian (79.0%), and the mean (standard deviation) age overall was 47.5 (15.3) years. The mean duration of constipation was 17.3 (15.0) years and 38.9% of patients had experienced chronic constipation for ≥ 20 years. Consistent with the results of the individual trials, significantly more patients achieved a mean of ≥ 3 SCBMs per week over 12 weeks of treatment in the prucalopride group (27.8%) than in the placebo group (13.2%, p < 0.001); the odds ratio was 2.68 (95% confidence interval: 2.16–3.33). Results were consistent in men and women, with response rates for prucalopride and placebo of 31.6% versus 16.7%, respectively, for men and 26.6% versus 12.2%, respectively, for women (both p < 0.001). At the final on-treatment assessment, the proportions of patients with an improvement of ≥ 1 point in the PAC-SYM and PAC-QOL total scores from baseline were 33.3% versus 23.9% and 37.1% versus 22.3%, respectively, in the prucalopride group versus the placebo group. Prucalopride showed a consistently good safety and tolerability profile. The most common adverse events were gastrointestinal disorders (nausea, diarrhoea and abdominal pain) and headache, mainly occurring at the start of treatment. No cardiovascular safety signals were identified. The safety and tolerability profile of prucalopride was similar in men and women.

Conclusion: This integrated analysis demonstrates the favourable efficacy and safety profile of prucalopride for the treatment of chronic constipation over 12 weeks in both men and women.

Disclosure of Interest: H. Piessevaux Lecture fee(s): Shire, Consultancy: Shire, M. Camilleri: None declared, Y. Yiannakou Lecture fee(s): Shire, Conflict with: educational grant from Shire, J. Tack Financial support for research: Abbott, Novartis and Shire, Lecture fee(s): Abbott, Almirall, AstraZeneca, Janssen, Menarini, Novartis, Shire, Takeda and Zeria., Consultancy: Almirall, AstraZeneca, Danone, GI Dynamics, GlaxoSmithKline, Ironwood Pharmaceuticals, Janssen, Menarini, Novartis, Rhythm, Shire, Takeda, Theravance, Tsumura, Will-Pharma and Zeria, E. Quigley Financial support for research: Rhythm and Vibrant, Lecture fee(s): Almirall, Ironwood, Metagenics, Procter and Gamble and Shire/Movetis, Consultancy: Alimentary Health, Almirall, Forest, Ironwood, Movetis, Rhythm, Salix, Shire and Vibrant, M. Ke Lecture fee(s): Janssen, S. Da Silva Conflict with: employee of Shire, A. Levine Shareholder: Shire, Conflict with: employee of Shire, R. Kerstens Consultancy: Shire, Conflict with: employee of Shire at the time of the study

P1068 NORMAL VALUES FOR 3D HIGH-RESOLUTION ANORECTAL MANOMETRY IN CHILDREN

M. Banasiuk¹, A. Banaszkiewicz¹, P. Albrecht¹

¹Pediatric Gastroenterology and Nutrition, Medical University of Warsaw, Warsaw, Poland

Contact E-mail Address: mbanasiu@tlen.pl

Introduction: 3D high-resolution resolution anorectal manometry is the most precise tool to assess function and 3D topographic picture of pressures along the anal canal. Until now, it has been used only in adult population. The normal values in pediatric population have not been evaluated so far.

Aims & Methods: The aim of this prospective study was 3D manometric evaluation of anorectal function in children without symptoms from lower gastrointestinal tract.

Manometry procedures were performed using a rigid probe (Covidien AG, Ireland) without premedication. Pressures within the anal canal and 3D picture of sphincters were obtained. The volume of balloon to elicit rectoanal inhibitory reflex (RAIR) was established. If possible, defecation dynamics and thresholds of sensation were evaluated. Data were expressed as mean (±SD).

Results: 61 children (34 males; age: 2-17 years, mean: 8.28 years) were studied. Mean resting and squeeze sphincter pressures were 83.43 (±23.23) mmHg and 191 (±64.21) mmHg, respectively. The mean length of the anal canal was 2.62 (±0.68) cm and it was correlated with age (r=0.49, p < 0.0001). Mean rectal balloon volume to elicit RAIR was 15.66 (±10.9) cc. The first sensation, urge and discomfort were observed at 24.42 (±23.98) ml, 45.91 (±34.55) ml and 91.58 (±50.17) ml of the balloon volume, respectively. Mean resting pressure of puborectalis muscle was 71.54 mmHg (±14.58), mean squeeze pressure was 134.10 mmHg (±35.2). There was no lesions of sphincters according to 3D topographic picture of the anal canal. There was no statistically significant differences in pressure profiles between males and females. Positive correlation between age and volume of balloon needed to elicit discomfort was found.

Conclusion: Normative data of 3D high-resolution anorectal manometry in children without symptoms from lower gastrointestinal tract were established. There were no significant gender differences concerning pressure results.

Disclosure of Interest: M. Banasiuk Conflict with: Equipment support from manufacturer (Covidien AG), A. Banaszkiewicz: None declared, P. Albrecht: None declared

P1069 THE CHRO.CO.DI.T.E. STUDY: MANAGEMENT OF CHRONIC CONSTIPATION IN GASTROENTEROLOGICAL EVERYDAY PRACTICE

D. Gambaccini¹, M. Bellini¹, P. Usai Satta², G. Bassotti³, R. Bocchini⁴, E. Battaglia⁵, F. Galeazzi⁶, A. Bove⁷, P. Alduini⁸, P. Portincasa⁹, D. Badiali¹⁰, M. C. Neri¹¹, N. Muscatiello¹², M. Di Stefano¹³, C. Giannelli¹⁴, L. Turco¹⁵, S. Camilleri¹⁶, G. Ceccarelli¹⁷, P. Iovino¹⁸, L. M. Montalbano¹⁹, S. Rentini²⁰, V. Savarino²¹, S. Segato²², G. Manfredi²³, M. Alessandri²⁴, R. Cannizzaro²⁵, F. Corti²⁶, R. Cuomo²⁷, F. Pucciani²⁸, C. Mellone²⁹, R. Roberta³⁰, L. D'Alba³¹, G. Milazzo³², M. Ruggeri³³

¹Cisanello University Hospital Pisa, Pisa, ²Brotzu Hospital, Cagliari, ³University of Perugia, Perugia, ⁴Malatesta Novello Hospital, Cesena, ⁵Cardinal Massaja Hospital, Asti, ⁶University of Padova, Padova, ⁷Cardarelli Hospital, Naples, ⁸Gastroenterology Unit, Lucca, ⁹University of Bari, Bari, ¹⁰La Sapienza University, Rome, ¹¹Pio Albergo Trivulzio, Milan, ¹²University of Foggia, Foggia, ¹³San Matteo Gastroenterology Unit, Pavia, ¹⁴San Camillo Hospital, Rome, ¹⁵Cupertino Gastrointestinal Unit, Cupertino, ¹⁶Gastrointestinal Unit, Caltanissetta, ¹⁷Endoscopic Centre, Massa, ¹⁸Gastrointestinal Unit, Salerno, ¹⁹Gastrointestinal Unit, Palermo, ²⁰Gastrointestinal Unit, Siena, ²¹University of Genoa, Genoa, ²²Gastrointestinal Unit, Varese, ²³Gastrointestinal Unit, Crema, ²⁴San Raffaele Hospital, Milan, ²⁵Aviano Oncologic Centre, Pordenone, ²⁶Gastrointestinal Unit, Viareggio, ²⁷Federico II Hospital, Naples, ²⁸Surgery Unit Careggi Hospital, Florence, ²⁹Gastrointestinal Unit, Montepulciano, Siena, ³⁰San Giuseppe Multimedica Hospital, Milan, ³¹San Carlo Hospital, Rome, ³²P. Borsellino Hospital, Marsala, Trapani, ³³Sant'Andrea Hospital, Rome, Italy

Contact E-mail Address: dario.gambaccini@gmail.com

Introduction: Chronic constipation (CC) comprises FC and IBS-C according to Rome-III-criteria, but some patients consider themselves constipated even not meeting these criteria (no Rome Constipation: NRC).

Aims & Methods: To evaluate clinical management of CC subgroups (FC, IBS-C, NRC) by 52 Italian gastroenterologists.

Results: Rome-criteria were routinely used by 45/52 of the gastroenterologists. Data from 918 CC patients were obtained (F: 80.5%; mean age: 51.1; FC: 61%; IBS-C: 31%; NRC: 8 %). The duration of CC was >10 years in 48%. Dyspepsia, anxiety/depression, gastroesophageal reflux and sleep disturbances were the most frequent comorbidities. Bristol 1-2 was reported in 71.6% of CC (FC: 71.8%; IBS-C: 75.6%; NRC: 48.1%; p < 0.001). Digital rectal examination was performed in 56.7%. Psychological consultation was requested in 11.4%, urological in 8.3% and gynecological in 12.4%. Diagnostic tests were requested in 79.6%: blood tests in 53.4%, thyroid function tests in 45% (FC: 43.2%; IBS-C: 52.4%; NRC: 35.2%; p < 0.005), colonoscopy in 38.7% (52.8% ≥50 years; 25.2%<50 years; p < 0.0001); anorectal manometry in 34.6% (FC: 38.6%; IBS-C: 29.8%; NRC: 22.2%; p < 0.01), colonic transit time in 25.8% and abdominal ultrasound in 21.8%. Dietary suggestions were prescribed in 80.4%; fibers in 54.9% (IBS-C: 60.7%; FC: 53.2%; NRC: 55.6%;), probiotics in 36.1%. Macrogol was suggested in 69% (FC: 70.9%; IBS-C: 71.6%; NRC: 42.6%). Antispasmodics were prescribed in 16.4% (IBS-C: 27.6%; FC: 11.6%; p < 0.0001). PAC-SYM (1.6 ± 0.7) was related to the duration of constipation (p < 0.005), to IBS-C and to an increased number of diagnostic tests (p < 0.001) and therapies (p < 0.05). PAC-QOL (1.78 ± 0.70) was related to IBS-C, to female sex (p < 0.05) and to an increased number of diagnostic tests (p < 0.05), specialist consultations (p < 0.005) and therapies (p < 0.0001).

Conclusion: NRC have a shorter history of disease, milder symptoms and require fewer diagnostic tests. PACSYM and PACQOL display higher values in IBS-C than in FC. Digital rectal examination is performed only in 57% of patients. Although not recommended by current guidelines, abdominal ultrasound is frequently requested. Macrogol is the most prescribed laxative both for FC and IBS-C.

Disclosure of Interest: None declared

P1070 AN AUDIT OF THE PREVALENCE OF FAECAL INCONTINENCE IN HOSPITAL PATIENTS

A. Gumber¹, M. Redman¹, M. ElSharif¹, G. Kaur¹

¹Surgery, Scunthorpe General Hospital, Scunthorpe, United Kingdom

Contact E-mail Address: gkaur@email.com

Introduction: Faecal incontinence (FI) is a common and under-reported problem, with many patients too embarrassed to seek help. Optimal management relies on first identification of these patients and only then- a thorough diagnosis that identifies all contributory factors, and a systematic approach to treatment. Management options include drug therapy, topical applications, containment products, behavioural techniques and surgery. Many patients do not receive optimal care due to lack of identification. In-hospital identification when they are admitted for other reasons may be one method of improving the care of such patients.

Aims & Methods: We assessed the identification of continence problems in our hospital patients via a simple ‘spot check’ audit of the different wards; we used the case notes for checking the documentation by both nursing and medical staff. We looked at care plans, stool charts, follow up plans etc.

Results: Overall, 163 patient case notes were examined. 90% had nursing documentation about faecal continence documented in comparison to 48% for medical documentation. Of the 147 patients where nursing documentation was found, 10.8% were found to have FI. Only 31% of these patients would have been identified by medical documentation. If only medical documentation had been used, this would have dropped to 6.5%. Most of the patients that were identified as having FI were, as expected, elderly and on the stroke unit (44%), general elderly medical wards (37.5%), orthopaedic (12.5%) and gastroenterology (6%) wards. All patients (100%) were then referred appropriately for further management.

Conclusion: Faecal incontinence has considerable impact on patients’ lifestyle and quality of life, and can cause profound distress. It is important to identify these patients with FI, establish the cause and initiate appropriate management, whilst maintaining their privacy and dignity. The impact of FI on the patient’s quality of life needs to be assessed prior to planning management/specialist referral etc. Written documentation in the form of care plans, follow up arrangements, advice leaflets etc is vital to providing optimal care for our patients. We found that our nursing documentation was much better than the medical documentation which needs to be improved. Once identified, all our patients were managed appropriately.

Disclosure of Interest: None declared

P1071 QUALITY AND EPIDEMIOLOGY OF CLINICAL PRACTICE GUIDELINES FOR CONSTIPATION: A SYSTEMATIC APPRAISAL

H. Tian¹, C. Ding¹, J. Gong¹, N. Li¹

¹Research Institute of General Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China

Contact E-mail Address: kevin_thl@163.com

Introduction: Clinical practice guidelines (CPGs) play an important role in healthcare. The guideline development process should be precise and rigorous to ensure that the results are reproducible and not vague. The main objective of our work was to identify published constipation guidelines and assess their quality with the Appraisal of Guidelines for Research and Evaluation instrument (AGREE) and their suitability regarding adaptation for future guidelines.

Aims & Methods: To assess the methodological quality and epidemiology of clinical practice guidelines on constipation. We performed a systematic literature search on constipation CPGs of five databases (included MEDLINE and EMBASE) and guideline websites were searched till to April, 2015. The methodological quality of the guidelines was assessed by four authors independently using the AGREEII instrument.

Results: From 1234 citations, 22 relevant guidelines were included. The overall agreement among reviewers was moderate (Intra-class correlation coefficient=0.84; 95% confidence interval [CI], 0.56-0.86). The mean scores were moderate for the domains “scope and purpose” (51.77) and ‘‘rigor of development’’(56.73), however, there were low for the domains ‘‘clarity of presentation’’ (23.73), ‘‘stakeholder involvement’’(32.23),‘‘applicability’’(29.14) and ‘‘editorial independence’’(29.59). Four sixths domains scores were lower when compared with international average level. According to the AGREE instrument, six guidelines can be strongly recommended, 10 with provisos and alterations while the remaining cannot be recommended for adaptation due to poor methodological quality.

Conclusion: Overall, the quality of the guidelines assessed was low when compared with the international CPGs average level. The quality and transparency of the development process and the consistency in the reporting of constipation guidelines need to be improved. Many other methodological disadvantages were identified. In the future, constipation CPGs should base on the best available evidence and rigorously developed and reported. Greater efforts are needed to provide high-quality guidelines that serve as a useful and reliable tool for clinical decision-making in this field.

Disclosure of Interest: None declared

P1072 LONG-TERM OUTCOME OF INFANTS WITH SUSPECTED HIRSCHSPRUNG'S DISEASE BUT NORMAL RECTAL BIOPSY

D. Graph¹, O. Kharenko¹, J. Waxman¹, T. Frankel¹, D. Turner¹, O. Ledder¹

¹Shaare Zedek Medical Center, Jerusalem, Israel

Contact E-mail Address: orenl@szmc.org.il

Introduction: Hirschsprung's disease (HD) must always be considered in very-early onset constipation. While HD has a well describes clinical course, little is known about those infants in whom HD was excluded.

Aims & Methods: We aimed to describe the long-term clinical outcomes of infants with clinical suspicion of HD which was excluded by rectal suction biopsy.

This is a single-center double-cohort comparative study. Infants who underwent rectal mucosa biopsy for suspected HD were age and gender-matched with healthy controls. A survey relating to clinical outcomes, stooling patterns and other gastrointestinal-related conditions was sent to parents. Pathology slides were re-reported by an experienced histopathologist blinded to the clinical data.

Results: A total of 51 infants were included (25 case, 26 control; median 51 months (IQR 32-83) months of follow-up). Nine (36%) of the case group required prolonged laxative use for constipation during the first year of life compared with 0 (0%) of controls (P < 0.001). Case infants were significantly more likely to be hospitalized or be diagnosed with a chronic gastrointestinal-related condition than controls (33% vs 12%, p=0.01; and 19% vs 8% respectively, p=0.04).

Abstract number: P1072

	Entire cohort (n=51)	Control group (n=26)	Study group (n=25)	p-value
Constipation1	18 (35%)	0 (0%)	18 (72%)	p < 0.001
Laxative Use2	9 (18%)	0 (0%)	9 (36%)	0.001
Vomiting3	13 (26%)	0 (0%)	13 (52%)	p < 0.001
Possiting4[t1]	4 (8%)	0 (0%)	4 (16%)	0.051
Abdominal Distention5	17 (33%)	1 (4%)	16 (64%)	p < 0.001
Abdominal Pain6	14 (28%)	0 (0%)	14 (56%)	p < 0.001
Increased Effort of defecation7	16 (31%)	1 (4%)	15 (60%)	p < 0.001
Use of Anal Stimulants8	18 (35%)	1 (4%)	17 (68%)	p < 0.001
Irritability9	23 (45%)	4 (15%)	19 (76%)	p < 0.001

¹ Defined as moderate or severe constipation

² Defined as using drugs for a period of 1 month or more

³ Defined as vomiting once a week or more often

⁴ Defined as many possiting, severe, beyond age of 6 months, which required treatment

⁵ Defined as moderate or severe abdominal distension

⁶ Defined as moderate or severe abdominal pain

⁷ Defined as moderate or severe effort of defecation

⁸ Defined as using anal stimulants at least once a week

⁹ Defined as moderate or severe unrest

Conclusion: Constipation in infancy is associated with long term gastrointestinal related disorders and should be considered clinically significant even when the diagnosis of HD is excluded. Infants with early onset abnormal stooling patterns should be monitored with adequate pediatrician or pediatric gastroenterologist follow-up.

Disclosure of Interest: None declared

P1073 IMPACT OF SWITCHING FROM A BRAND TO A GENERIC MACROGOL ON PRESCRIPTIONS AND DOSES FOR PATIENTS WITH CHRONIC CONSTIPATION IN THE UK

V. Bajaj¹, A. Naidoo¹

¹Norgine Limited, Uxbridge, United Kingdom

Contact E-mail Address: vbajaj@norgine.com

Introduction: Patients with constipation switching from a branded to a generic macrogol may require a higher number of prescriptions and doses (defined as packs of 20 sachets). Repeated switching on the basis of cost savings alone can irritate patients and can erode trust and compliance (GPC 2013¹).

Aims & Methods: This analysis compares prescription numbers and doses (20 sachets/pack) for chronic constipation patients switched from branded macrogol (MOVICOL) to generic macrogol (LAXIDO), and those who switched back. Retrospective real-world, longitudinal patient and prescribing data from 397 UK GP practices (2,186 GPs, 13,567 patients; Jan-Dec 2013; Cegedim Strategic Data Ltd, a division of IMS Health) were analysed in two cohorts of chronic constipation patients: (1) patients prescribed branded macrogol, switched to generic; (2) patients prescribed branded macrogol, switched to generic (Switch-1) and returned to the brand (Switch-2). All patients were tracked from initiation to treatment end. Annualised prescriptions and doses/patient changes in each cohort were analysed (one- and two-sided t-test for two-sample assuming unequal variances).

Results: Males/females aged ≥13 years were analysed. In cohort (1), N=3109, M=0.63, SD=8.29, prescription numbers (+8%) and doses (+13%) per patient/year showed an average increase. Absolute increase in prescription numbers (+0.6) and doses (+1.7) were significant (p < 0.05), and observed across all age groups (elderly [65+], middle-aged [36-64], young adult [19-35], adolescent [13-18]). In cohort (2), N=91, M=-3.41, SD=1.65, prescription numbers (-24%) and doses (-11%) per patient/year showed an average reduction during Switch-2. Additionally, absolute increase in prescription numbers (+5.0) and doses (+4.9) at Switch-1 was significant (p < 0.05).

Conclusion: Chronic constipation patients switched from branded to generic macrogol required a significantly higher number of prescriptions and doses than previously required. Patients who switched back from the generic to the branded macrogol required fewer. Factors impacting changes in prescription e.g. efficacy, convenience, and compliance require further investigation.

This analysis was funded by Norgine.

Disclosure of Interest: V. Bajaj Conflict with: Employee of Norgine, A. Naidoo Conflict with: Employee of Norgine

P1074 EFFECT OF PRUCALOPRIDE ON SYMPTOMS OF CHRONIC CONSTIPATION IN MEN AND WOMEN: AN INTEGRATED ANALYSIS OF SIX RANDOMIZED CONTROLLED CLINICAL TRIALS

Y. Yiannakou¹, H. Piessevaux², M. Camilleri³, J. Tack⁴, E. M. Quigley⁵, M. Ke⁶, S. da Silva⁷, A. Levine⁸, R. Kerstens⁹

¹County Durham and Darlington NHS Foundation Trust, Durham, United Kingdom, ²Cliniques Universitaires Saint-Luc, Brussels, Belgium, ³College of Medicine, Mayo Clinic, Rochester, United States, ⁴TARGID, University of Leuven, Leuven, Belgium, ⁵Houston Methodist Hospital, Houston, United States, ⁶Peking Union Medical College Hospital, Bejing, China, ⁷Shire, Brussels, Belgium, ⁸Shire, Wayne, United States, ⁹Orion Statistical Consulting BV, Hilvarenbeek, Netherlands

Contact E-mail Address: Yan.Yiannakou@cddft.nhs.uk

Introduction: Prucalopride, a highly selective 5-hydroxytryptamine receptor-4 agonist, stimulates intestinal motility and is effective at alleviating symptoms of chronic constipation (CC).

Aims & Methods: This analysis aimed to compare the effect of prucalopride ≤ 2 mg on constipation symptoms in men and women, using the validated Patient Assessment of Constipation-Symptoms (PAC-SYM) questionnaire. An integrated analysis was performed on data from six phase 3 and 4, multicentre, double-blind, randomized, placebo-controlled, parallel-group trials investigating the efficacy and safety of prucalopride in CC. All six studies had similar study designs, allowing pooling of results and sex-specific sub-analyses. The treatment period was 12 weeks in five of the six studies, and 24 weeks in the sixth study.

Results: Overall, 2484 patients (597 men, 1887 women) were included in the analysis. Of these, 1237 received prucalopride and 1247 received placebo. The mean (standard deviation) age was 47.5 (15.3) years and duration of constipation was 17.3 (15.0) years. For both men and women at baseline, stool symptoms were rated greater in severity (moderate to severe) than abdominal and rectal symptoms (mild to moderate for both). The mean decrease in overall PAC-SYM score from baseline to final on-treatment assessment (FoTA) was significantly greater for men and women in the prucalopride group (both, –0.7) than in the placebo group (men, –0.5, p = 0.019; women, –0.4, p < 0.001) (Table). The proportion of patients with a change of ≥ 1 point in overall PAC-SYM score at FoTA was quantitatively greater for men and women in the prucalopride group (men, 31.1%; women, 33.9%) than in the placebo group (men, 24.5%; women, 23.7%); similar results were reported for all subscores.

Abstract number: P1074 Table.

PAC-SYM scores.

PAC-SYM score,mean observed (mean change from BL)	Placebo				Prucalopride ≤ 2 mg
	Women		Men		Women			Men
n	Score	n	Score	n	Score	p value*	n	Score	p value*
Overall scoreBLFoTA	944938	1.91.5 (–0.4)	296290	1.71.2 (–0.5)	939927	1.91.2 (–0.7)	< 0.001	295285	1.81.1 (–0.7)	0.019
Stool symptomsBLFoTA	943938	2.41.9 (–0.5)	296290	2.21.7 (–0.6)	938927	2.41.6 (–0.8)	< 0.001	295285	2.31.5 (–0.8)	0.013
Abdominal symptomsBLFoTA	944937	1.91.4 (–0.4)	296290	1.51.0 (–0.5)	938928	1.91.2 (–0.7)	< 0.001	295285	1.61.0 (–0.6)	0.336
Rectal symptomsBLFoTA	943937	1.10.8 (–0.3)	293290	1.00.7 (–0.4)	937927	1.20.7 (–0.5)	< 0.001	295285	1.10.6 (–0.5)	0.061

*Placebo versus prucalopride. Based on a Cox proportional hazard regression including terms for treatment group, study, country, number of complete bowel movements at baseline (0 or > 0) and sex.

BL, baseline; FoTA, final on-treatment assessment; PAC-SYM, Patient Assessment of Constipation-Symptoms.

Conclusion: The symptoms of CC improved in both men and women receiving prucalopride, as assessed using PAC-SYM scores.

Disclosure of Interest: Y. Yiannakou Lecture fee(s): Shire, Conflict with: educational grant from Shire, H. Piessevaux Lecture fee(s): Shire, Consultancy: Shire, M. Camilleri: None declared, J. Tack Financial support for research: Abbott, Novartis and Shire, Lecture fee(s): Abbott, Almirall, AstraZeneca, Janssen, Menarini, Novartis, Shire, Takeda and Zeria., Consultancy: Almirall, AstraZeneca, Danone, GI Dynamics, GlaxoSmithKline, Ironwood Pharmaceuticals, Janssen, Menarini, Novartis, Rhythm, Shire, Takeda, Theravance, Tsumura, Will-Pharma and Zeria, E. Quigley Financial support for research: Rhythm and Vibrant, Lecture fee(s): Almirall, Ironwood, Metagenics, Procter and Gamble and Shire-Movetis, Consultancy: Alimentary Health, Almirall, Forest, Ironwood, Movetis, Rhythm, Salix, Shire and Vibrant, M. Ke Lecture fee(s): Janssen, S. da Silva Conflict with: employee of Shire, A. Levine Shareholder: Shire, Conflict with: employee of Shire, R. Kerstens Consultancy: Shire, Conflict with: employee at Shire at the time of the study

P1075 SYSTEMATIC REVIEW OF QUALITY OF PATIENT INFORMATION ON COLORECTAL CANCER SCREENING ON THE INTERNET

E. H. Schreuders¹, E. J. Grobbee¹, E. J. Kuipers¹, M. C. Spaander¹, S. J. Veldhuyzen van Zanten²

¹Gastroenterology and Hepatology, Erasmus MC, Rotterdam, Netherlands, ²Division of Gastroenterology, University of Alberta, Edmonton, Canada

Contact E-mail Address: e.schreuders@erasmusmc.nl

Introduction: Efficacy of colorectal cancer (CRC) screening programs is dependent on screenees’ participation. The internet is increasingly used by individuals for health information and can be an important tool to support decision making. The aim was therefore to evaluate the accuracy, quality and readability of patient-oriented websites on CRC screening.

Aims & Methods: Websites were identified by Google.com™ using the search term: “colorectal cancer screening” OR “bowel cancer screening” OR “colon cancer screening”. To assess accuracy, a Quality Evaluation Instrument (QIE) was developed and pretested, which awards points (0-44) on various aspects of CRC screening. In addition, websites were evaluated using a validated five-point Global Quality Score (GQS), two validated internet quality instruments (LIDA; 0-100% and DISCERN;16-80) and two reading scores; Flesch Reading Ease (FRE) and Flesch-Kincaid Grade Level (FKG). Since internet searchers do not typically view more than one page and usually choose one of the first results displayed by the search engine, two raters independently assessed the first 3 Google pages totaling 30 websites. Portal links to other sites, duplicates and news articles were excluded. For QEI assessment, consensus in case of disagreement was achieved through discussion with a third reviewer. For other parameters the mean score of both website raters was used.

Results: Out of the first 30 hits, 20 websites met the inclusion criteria. The mean QEI score was 25.5 (range 9-41) and the median GQS was three (range 2-5). There was a strong positive correlation between the QEI and the validated GQS (Spearman’s r=0.81; p < 0.001). Also the validated LIDA and DISCERN had a moderate correlation with the QEI; r_s=0.45 (p=0.05) and r_s=0.65 (p < 0.01) respectively. There was no correlation between the Google rank and QEI (r_s=-0.36; p=0.12). The mean FRE was 48 (range 27–76). Only 30% of the websites had a reading level acceptable for the general public (FRE> 60). The mean FKG was 11 (range 5.4–15.9), indicating the text would be understandable to an average 11^th grade US student. The mean LIDA overall score was 68% (range 25-86%) and the mean DISCERN score was 46 (range 27-68).

Abstract number: P1075 Table 1.

Top 5 accuracy websites with corresponding scores and Google rank positions.

Website	Accuracy	Quality			Readability		Google rank
	QEI(0-44)	GQS(1-5)	DISCERN(16–80)	LIDA(0-100%)	FRE	FKG
www.cancer.org	41	5	65	67%	62	9th	6
www.bowelcanceraustralia.org	38	3	35	58%	58	10th	5
www.uptodate.com	37	5	69	85%	28	14th	27
www.macmillan.org.uk	35	4	49	69%	48	11th	19
www.nlm.nih.gov/medlineplus	34	4	57	81%	59	8th	4

Conclusion: There is marked variation in quality of websites on CRC screening. The developed QEI was strongly correlated with previously validated quality instruments, making it a valuable tool to identify high-quality, accurate CRC screening websites. Notable is the poor correlation between quality and Google ranking. As people generally only read the first 10 hits, our findings suggest that they will miss out on high quality CRC screening websites. Improvements in quality and readability are required to provide patients with reliable information to make informed decisions on CRC screening participation.

Disclosure of Interest: None declared

P1076 GUAIAC-BASED FAECAL OCCULT BLOOD TESTS VERSUS FAECAL IMMUNOCHEMICAL TESTS FOR COLORECTAL CANCER SCREENING IN AVERAGE-RISK INDIVIDUALS

E. J. Grobbee¹, E. H. Schreuders¹, A. H. van Roon¹, L. van Dam¹, A. G. Zauber², I. Lansdorp-Vogelaar³, G. J. Borsboom³, E. W. Steyerberg³, M. E. van Leerdam⁴, M. C. Spaander¹, E. J. Kuipers¹

¹Gastroenterology and Hepatology, Erasmus MC, Rotterdam, Netherlands, ²Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, United States, ³Public Health, Erasmus MC, Rotterdam, ⁴Gastroenterology and Hepatology, Netherlands Cancer Institute, Amsterdam, Netherlands

Contact E-mail Address: e.grobbee@erasmusmc.nl

Introduction: Faecal occult blood tests (FOBT) to screen for colorectal cancer (CRC) fall into two main categories: a guaiac-based FOBT (gFOBT) or the more recently developed faecal immunochemical test (FIT). More evidence has become available about FOBT screening which suggests that FIT may be superior to the commonly used gFOBT. The aim of this systematic review was to compare the diagnostic test accuracy of FIT and gFOBT screening for detecting advanced neoplasia (AN) and CRC in average-risk individuals.

Aims & Methods: This abstract is based on a pre-peer review of a formal Cochrane Review. Upon completion and approval, the final version of the manuscript is expected to be published in the Cochrane Database of Systematic Reviews. Studies were identified by searching electronic databases Medline, Embase, Cochrane Library, BIOSIS Citation Index, and SCI-expanded (31 January 2015) without restrictions on date or language. We included randomized and/or comparative studies in which asymptomatic average-risk individuals ≥ 40 years of age underwent gFOBT and/or FIT screening. Studies in which all participants underwent both a FOBT followed by colonoscopy were included. Data were analysed using a bivariate linear mixed model (Reitsma et al., 2005). Results of the tests reporting a cutoff of 10 mcg Hb/g faeces (FIT10) or 20 mcg Hb/g (FIT20) are shown.

Results: The search identified 5,355 titles, of which 526 were fully assessed and 23 studies were included. Seven studies compared more than one test and in 6/7 studies participants underwent more than one test; resulting in a total of 32 tests in 85,403 participants. For 11 FITs the data for FIT10 were retrieved, and for 8 FITs data for FIT20. All included gFOBT studies used a cutoff of at least one positive card. The sensitivity for detection of AN ranged between studies from 0% to 33% for gFOBT, from 5% to 67% for FIT10, and from 50 to 100% for FIT20. Sensitivity for AN was lower for gFOBT with a pooled sensitivity of 16%, compared to 32% for FIT10 (p = 0.001), and 27% for FIT20 (p=0.007). Sensitivity for CRC ranged between studies from 57% to 67% for gFOBT, from 75% to 100% for FIT10, and from 63% to 94% for FIT20. Sensitivity for CRC was lower for gFOBT with a pooled sensitivity of 41%, compared to 80% for FIT10 (p=0.003), and 72% for FIT20 (p=0.002). No significant differences in specificity were found for AN between gFOBT (94%), FIT10 (95%) and FIT20 (96%), nor for CRC between gFOBT (94%), FIT10 (93%) and, FIT20 (93%).

Conclusion: This meta-analysis shows that FIT is superior to gFOBT in detecting advanced neoplasia and colorectal cancer in average-risk individuals. The specificity of both tests is similar. These results strongly support the current European guidelines for implementing FIT-based CRC screening programs and the switch from gFOBT to FIT testing for existing programs.

Disclosure of Interest: None declared

P1077 COMPARISON OF OC-SENSOR AND FOB-GOLD IN POPULATION BASED COLORECTAL CANCER SCREENING BASED ON FIT

E. J. Grobbee¹, M. van der Vlugt², A. J. van Vuuren¹, A. K. Stroobants³, P. Didden¹, M. W. Mundt⁴, P. M. Bossuyt⁵, I. Lansdorp-Vogelaar⁶, E. J. Kuipers¹, M. C. W. Spaander¹, E. Dekker²

¹Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, ²Gastroenterology and Hepatology, ³Clinical chemistry, Academic Medical Centre Amsterdam, Amsterdam, ⁴Gastroenterology and Hepatology, Flevoziekenhuis, Almere, ⁵Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre Amsterdam, Amsterdam, ⁶Public Health, Erasmus MC University Medical Centre, Rotterdam, Netherlands

Contact E-mail Address: e.grobbee@erasmusmc.nl

Introduction: Colorectal cancer (CRC) screening programs are implemented worldwide and many are based on fecal immunochemical testing (FIT). Data on participation and yield over consecutive rounds of FIT screening are limited. In the Netherlands, pilot-studies have been performed with OC-sensor (Eiken, Japan) and the recently started nationwide program is using FOB-Gold (Sentinel, Italy). Yet, little evidence is available how these two tests compare. The aim of this study was to evaluate the two tests on usability, participation and diagnostic yield.

Aims & Methods: The comparison was performed in the 4^th round of a population-based FIT-screening cohort in the Netherlands. Demographic data of randomly chosen 20.000 individuals between 50-74 years living in the Amsterdam and Rotterdam regions of the Netherlands were obtained from municipal population registers (March 2014 to December 2014). All invitees in previous biennial rounds were re-invited except for those who tested positive in earlier rounds or those passing the upper age limit. Invitees were randomized to receive an OC-sensor or an FOB-Gold test. The test was considered positive if hemoglobin concentration was ≥10 µg Hb/g feces. Participation rate, positivity rate, and positive predictive value (PPV) for advanced neoplasia (AN) and CRC were calculated. The detection rate was defined as the proportion of participants being diagnosed with AN.

Results: In total 19,290 eligible persons (median age 61, IQR 57-67; 48% males) were invited: 9,669 invitees received the OC-sensor and 9,621 the FOB-Gold test: 62.4% returned the OC-sensor and 62.5% the FOB-Gold test (n.s.). Inappropriate use or unanalyzable tests occurred in 0.7% invitees using the OC sensor vs. 1.9% invitees using FOB-Gold test (p < 0.001). For OC-sensor, 7.9% were positive, compared to 6.5% for FOB-Gold (p=0.002). The PPV for AN in the OC-sensor group was 31.2% (95% CI:27.1-38.5), versus 32.1% in the FOB-Gold group (95% CI: 27.5-37.3) (n.s.). The detection rate was slightly higher for OC-sensor 2.2%, than for the FOB-Gold 1.9% (n.s.).

	Total	OC-sensor	FOB-Gold	p
Participation rate (%)	62.4	62.4	62.5	n.s.
Unanalyzable tests* (%)	1.3	0.7	1.9	< 0.001
Positivity rate (%)	7.2	7.9	6.5	0.002
Detection rate
AN (%)	2.1	2.2	1.9	n.s.
CRC (%)	0.2	0.2	0.2	n.s.
Positive predictive value
AN (%)	31.6	31.2	32.1	n.s.
CRC (%)	3.5	3.0	4.0	n.s.
True positives (AN) per 1000 invited (n)	12	13	11

Conclusion: In this fourth round of biennial population based FIT-screening, both FITs OC-sensor and FOB-Gold seemed comparable regarding participation rate and positive predictive value. Significant differences between the tests were found on unanalyzable tests, with more additional FOB-Gold tests needed to be sent to invitees due to inappropriate use, and positivity rate, resulting in more colonoscopies to be performed for a positive OC-sensor.

Disclosure of Interest: None declared

P1078 HOW OFTEN DO THE PATIENT REPEAT SCREENING COLONOSCOPY? ; A STUDY FOR PERSONALIZED RECOMMENDATION OF SCREENING COLONOSCOPY INTERVAL

E. S. Kim¹, H. J. Chun¹, I. K. You¹, S. H. Kim¹, J. M. L. Lee¹, H. S. Choi¹, B. Keum¹, Y. T. Jeen¹, J. Gu², S. B. Kim²

¹gastroenterology, Korea University College of Medicine, ²Department of Industrial Management Engineering, Korea University, Seoul, Republic of Korea

Contact E-mail Address: silverkes@naver.com

Introduction: Colorectal cancer (CRC) is the third most common cancer and the second most frequent cause of cancer death of female and fourth most of male in South Korea. Most CRCs develop through the adenoma–carcinoma sequence, which allows for screening and prevention of CRCs by screening colonoscopic examination and polypectomy. However, there have been limited data on personalized optimal time interval of next surveillance colonoscopic examination. The aim of our study is to recommend personalized interval by analysis of various clinical factors obtained by health care examination.

Aims & Methods: We enrolled the patients who underwent two times more voluntary, complete screening colonoscopy at health care unit of Korea University Medical Center Anam Hospital from July 1, 2004 to July 31, 2010. The clustering analysis using the partitioning around medoids algorithm and Hierarchial cluster were conducted including the 32 clinical, geographic and laboratory data. For each cluster, we then performed survival analysis that provides the probability of having polyps according to the number of days until next colonoscopy.

Results: Totally 8332 patients underwent screening colonoscopy, among them 625 patients performed repeat colonoscopy exam. 625 patients divided four clusters by clustering analysis. Adenoma detection at first screening colonoscopy was the most potent risk factor of develop of adenoma at next screening. Male gender, triglyceride (>134 mg/dL), and age (>56 years old) were significant factor for decision of the personalized interval of next screening colonoscopy. For example, male patient, who had adenoma at fist screening, the predicted risk of adenoma is 50% after 25 months.

Conclusion: Our study can provide personalized time interval of next screening colonoscopy according to patients’ individual clinical data. Further study are necessary for validation our results.

Disclosure of Interest: None declared

P1079 URSODEOXYCHOLIC ACID AND RISK OF COLORECTAL CANCER: A POPULATION-BASED COHORT STUDY IN TAIWAN

F.-M. Chang^1,2,*, Y.-P. Wang^2,3, H.-C. Lin^1,2, H.-C. Lang⁴, C.-L. Lu^1,2

¹Division of Gastroenterology, Taipei Veterans General Hospital, ²Department of Medicine, National Yang-Ming University, ³Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, ⁴Health Care Administration, National Yang-Ming University, Taipei City, Taiwan, Province of China

Contact E-mail Address: formos337@yahoo.com.tw

Introduction: Whether Ursodeoxycholic acid (UDCA) has a chemopreventive role or not for colorectal cancer (CRC) remains unclear. UDCA has been efficiently employed as a cytoprotective agent in vitro and is reported to prevent CRC in patients with primary sclerosing cholangitis and ulcerative colitis.^1,2 In contrary, a recent study showed that high doses of UDCA was associated with increased CRC risk for similar groups of patients.³ Many patients with chronic hepatitis has been prescribed with off-label use of UDCA in Taiwan, a high endemic country for chronic viral hepatitis B.

Aims & Methods

Aims: We sought to investigate the association between UDCA therapies and CRC.

Methods: A nationwide cohort population-based study was performed using the Taiwan National Health Insurance Research Database. Patients who were taking UDCA from years 1998-2007 and were ≥ 20-year-old from one million beneficiaries were enrolled. Those patients with antecedent malignancy or taking insufficient UDCA (UDCA ≤ 28 prescribed daily dose (P.D.D.) or 300mg/day) were excluded. For a sensitivity analysis, those CRC patients found within 1 year of the first dose of UDCA were also excluded. Propensity scores were used to match the UDCA users (treated cohort) with UDCA-nonusers at a 1:1 ratio, based on age, gender, comorbidities and medications. Both groups were followed until CRC diagnosis or the end of year 2010.

Results: 7,328 UDCA users were identified to take more than 28 P.D.D. After matched by propensity score, 5,385 patients in treated and control cohorts were identified for final analysis. The median follow-up time was 7.3 ± 2.9 years. The hazard ratio of CRC development for UDCA-users over non-users after adjustment for propensity score was 0.772 (95% C.I. 0.222-2.685). For patients taking 28-84 P.D.D.,85-179 P.D.D., 180-364 P.D.D., and ≥ 365 P.D.D., the hazards ratio for CRC were 0.774 (95% C.I. 0.365-1.64), 0.717 (95% C.I. 0.247-2.087), 0.738 (95% C.I. 0.220-2.471), and 1.372 (95% 0.554-3.400), respectively. The results suggested that no dose-responsive curve could be observed between hazards ratio for CRC and UDCA dosage.

Conclusion: In this nation-wide survey, the largest cohort till now, there existed no evidence to support the chemopreventive role of UDCA in CRC. Routine use of UDCA to prevent CRC is not recommended.

Disclosure of Interest: None declared

P1080 A RANDOMIZED CONTROLLED TRIAL OF AN EDUCATIONAL VIDEO TO IMPROVE QUALITY OF BOWEL PREPARATION FOR COLONOSCOPY

H. Kim¹, J. Park¹, M. Kim¹, K. Kwon¹

¹Internal Medicine, Inha University Hospital, Incheon, Republic of Korea

Contact E-mail Address: kimhg@inha.ac.kr

Introduction: High-quality bowel preparation is necessary for colonoscopy. A few studies have been conducted to investigate improvement in bowel preparation quality through patient education. The reported methods for patient education on bowel preparation are various, however have not been well studied. The aim of this study is to evaluate the effect of our own educational video for bowel preparation.

Aims & Methods: A randomized and prospective study was conducted. All patients received regular instruction for bowel preparation during a pre-colonoscopy visit. Those scheduled for colonoscopy were randomly assigned to view an educational video instruction (video group) on the day before the colonoscopy, or to a non-video (control) group. Qualities of bowel preparation using the Ottawa Bowel Preparation Quality scale (Ottawa score) were compared between the video and non-video groups. In addition, factors associated with poor bowel preparation were investigated.

Results: A total of 502 patients were randomized, 250 to the video group and 252 to the non-video group. The video group exhibited better bowel preparation (mean Ottawa total score: 3.03 ± 1.9) than the non-video group (4.21 ± 1.9; P < 0.001) and had poorer bowel preparation (total Ottawa score ≥6: 91.6% vs. 78.5%; P < 0.001). Multivariate analysis revealed that males (odds ratio [OR] = 1.95, P = 0.029), diabetes mellitus patients (OR = 2.79, P = 0.021), and non-use of visual aids (OR = 3.09, P < 0.001) were associated with poor bowel preparation.

Conclusion: The addition of an educational video significantly improved the quality of bowel preparation.

Disclosure of Interest: H. Kim Financial support for research: SK phamaceutical company, J. Park: None declared, M. Kim: None declared, K. Kwon: None declared

P1081 ECONOMIC BURDEN AND QUALITY OF LIFE OF MODERATE-TO-SEVERE IRRITABLE BOWEL SYNDROME WITH CONSTIPATION (IBS-C) IN EUROPE: POOLED RESULTS FROM THE IBIS-C STUDY

J. Tack¹, V. Stanghellini², F. Mearin³, Y. Yannakou⁴, P. Layer⁵, B. Coffin⁶, M. Simren⁷, J. Mackinnon⁸, J. Bertsch⁸, J. Fortea⁹

¹University Hospital Gasthuisberg, Leuven, Belgium, ²University of Bologna, Bologna, Italy, ³Centro Médico Teknon, Barcelona, Spain, ⁴University Hospital of North Durham, Durham, United Kingdom, ⁵Israelitic Hospital, Hamburg, Hamburg, Germany, ⁶Louis-Mourier Hospital, Colombes, France, ⁷Sahlgrenska University Hospital, Göteborg, Sweden, ⁸TFS Develop S. L., Barcelona, Spain, ⁹Almirall S. A., Barcelona, Spain

Contact E-mail Address: cristina.ceballos@tfscro.com

Introduction: This is the first study to assess the socio-economic burden of moderate-to-severe IBS-C in six European countries (France, Germany, Italy, Spain, Sweden and UK). Here we present the pooled economic and quality of life (QoL) results from all participating countries.

Aims & Methods: Observational, retrospective-prospective (6 months each) study of patients diagnosed in the last five years with IBS-C (Rome-III criteria) and with moderate-to-severe disease at inclusion (IBS-Symptom Severity Scale [IBS-SSS] score ≥ 175). The primary objective was to determine annual direct and indirect costs. Secondary objectives included assessing QoL at baseline: IBS-QoL and EuroQoL-5D (EQ-5D) questionnaires. Work productivity was assessed using the Work Productivity and Activity Impairment:IBS-C questionnaire (WPAI:IBS-C). All costs were calculated in local currency and adjusted (for inflation) to 2012 values. Post-hoc currency conversion was performed for cost comparison purposes.

Results: 525 patients were included in the study (60% severe by IBS-SSS); mean (±SD) age 45.3 ± 15.8 years, 86.9% female. The most prevalent symptoms at baseline were constipation (85.7%) and abdominal pain (85.1%). In the week prior to baseline, mean presenteeism (WPAI:IBS-C) was: 36.5%±29.0% of time; absenteeism: 8.4%±21.4%; work productivity loss: 39.4%±30.1%; daily activity impairment: 44.2%±28.6%. Mean IBS-QoL was 54.9 ± 22.7 (scale: 0-100 [worst-to-best]; 63.3 Italy–42.8 UK). Mean EQ-5D was 55.5 ± 21.7 (scale: 0-100 [worst-best]) and 89.4% and 62.3% of patients reported moderate-to-severe problems in pain/discomfort and anxiety/depression, respectively. Over the year, 73.1% patients consulted a primary care physician (88.4% UK–58.0% Italy), and 89.7% a gastroenterologist (100% France, Italy, UK–69.6% Germany); mean 4.9 (6.9 UK–2.1 Sweden) and 2.8 (4.0 Germany–1.7 Sweden) visits, respectively. 18.1% (24.0% UK–11.1% Sweden) patients required emergency department visits/hospitalisation (mean stay: 13.8 ± 24.0 days) and 62.1% had a diagnostic test (mean: 4.0 ± 2.7 [4.1 Spain–3.4 France, Italy]). 65.3% (90.4% UK–41.1% Italy) of patients took prescription drugs for their IBS-C and 67.2% (82.1% Italy–56.3% Spain) took non-prescription drugs. The mean annual direct costs per patient for national healthcare systems: €2,108 (UK) – €937 (Italy); cost for the patient: €568 (Spain) – €244 (France); indirect cost: €11,249 (Sweden) – €339 (Italy). Total annual cost: €12,827 (Sweden) – €1,761 (Italy).

Conclusion: Moderate-to-severe IBS-C symptoms have a high impact on QoL and work productivity of patients. With current management practices, both direct and indirect costs were high for all participating countries. Differences in annual direct costs were due to differences in healthcare resource utilisation, mainly diagnostic tests and medical consultations. Hospitalisations and/or emergency room visits was the largest direct cost driver for all countries.

Disclosure of Interest: J. Tack Conflict with: Grants / research support: Abbott, Novartis, Shire. Honoraria / consultancy fees: Almirall, AstraZeneca, Danone, GI Dyamics, GlaxoSmithKline, Ironwood, Janssen, Menarini, Novartis, Rhythm, Shire, Takeda, Theravance, Tsumura, Will Pharma, Zeria. Speaker fees: Abbott, Almirall, AstraZeneca, Janssen, Menarini, Novartis, Shire, Takeda, Zeria, V. Stanghellini Conflict with: Grants / research support: Alfa Wassermann, Almirall, Aptalis, Italchimici, Norgine, Shire, Takeda, Valeas. Honoraria / consultancy fees: Abbott, Alfa Wasserman, Almirall, Angelini, Aptalis, CM&D Pharma, Farmaderma, Ironwood, Norgine, Shire, Takeda, Valeas, Vibrant, Zeria., F. Mearin Conflict with: Speaker fees: Almirall., Y. Yannakou Conflict with: Grants: Shire; Medtronic. Speaker fees: Almirall; Shire; Sucampo., P. Layer Conflict with: Abbott / Solvay, Almirall, Aptalis / Axcan, Norgine, Shire., B. Coffin Conflict with: Honoraria / consultancy fees: Almirall, Mundipharma, Mayoly Spindler, Menarini., M. Simren Conflict with: Unrestricted research grants: Danone, AstraZeneca. Consultant/Advisory Board member: Danone, Nestlé, Chr Hansen, Almirall, Albireo, Shire. Participation in a company-sponsored speaker’s bureau: Almirall, Shire, Tillotts, Takeda., J. Mackinnon Conflict with: Employee of TFS Develop S. L, contracted by Almirall S. A to conduct the study., J. Bertsch Conflict with: Employee of TFS Develop S. L, contracted by Almirall S. A to conduct the study, J. Fortea Conflict with: Employee of Almirall, S. A

P1082 CORRELATION BETWEEN INFORMATION QUALITY IN REFERRAL LETTERS ASSESSED ON A NOVEL THIRTY POINT SCORE AND A VISUAL ANALOGUE SCALE: AN OBSERVATIONAL STUDY

S. L. Eskeland¹, L. Aabakken², C. Brunborg³, T. de Lange¹

¹Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Bærum, ²Department of Gastroenterology, ³Unit for Biostatistics, Epidemiology and Health Economics, Oslo University Hospital, Oslo, Norway

Contact E-mail Address: seskeland@hotmail.com

Introduction: Assessing referrals can be challenging if the content of the referral letter is inadequate. There is a lack of knowledge regarding which information is essential in referral letters to gastroenterologists.

Aims & Methods: The aim of the study was to create a score to assess the quality of information in referrals to gastroenterology departments in Norway. A secondary aim was to assess whether this score correlates to the gastroenterologists’ subjective assessment of the referral. 25 gastroenterologists participated in a survey regarding important information in referral letters. They were asked to select the 15 most important variables for 9 common indications. Each variable was assigned either 3, 2 or 1 points according to importance. The result was used to create a thirty point score (TPS). Subsequently, 327 referral-letters were collected from 7 primary gastroenterology referral centers. The quality of the information in the referral-letters was subjectively assessed on a 10 cm Visual Analogue Scale (VAS) and then assessed using the TPS. Pearson correlation analyses were performed to measure the association between the VAS and the TPS.

Results: The 327 referrals had an average score of 13.2(range 1-25) and an average VAS of 4.7(range 0.2-9.5). The overall correlation between the TPS and the VAS was moderate(r=0.42)(table 1). However, it ranged from fair(r=0.24) to substantial(r=0.70) for the various indications.

Table 1.

Comparison of referral information quality assessed by VAS and TPS.

Reason for referral	N. referrals (%)	Mean score(95% CI)	Mean VAS (95% CI)	Correlation coefficient	P
Abdominal pain	50 (15.3)	12.6 (11.0-14.2)	4.5 (3.9-5.2)	0.70	0.001
Dyspepsia	47 (14.4)	11.8 (10.6-13.0)	4.3 (3.7-4.9)	0.27	0.069
Hematochezia	34 (10.4)	15.4 (13.8-17.0)	5.1 (4.4-5.9)	0.48	0.004
Change of bowel habit	48 (14.7)	14.8 (13.4-16.3)	5.1 (4.4-5.8)	0.58	<0.001
Diarrhoea	38 (11.6)	11.3 (9.9-12.7)	4.6 (4.0-5.2)	0.38	0.019
Dysphagia	36 (11.0)	11.2 (9.6-12.8)	5.0 (4.3-5.8)	0.29	0.089
Constipation	27 (8.3)	13.6 (12.2-15.0)	4.5 (3.8-5.1)	0.23	0.255
Weight Loss	21 (6.4)	14.9 (12.5-17.2)	4.8 (3.9-5.8)	0.63	0.002
Jaundice	26 (8.0)	14.3 (12.4-16.2)	4.9 (3.9-5.8)	0.24	0.236
Total	327	13.2 (12.6-13.7)	4.7 (4.5-5.0)	0.42	<0.001

Correlation coefficient interpretation: 0-0.2=slight, 0.2-0.4=fair 0.4-0.6=moderate, 0.6-0.80= substantial, 0.8-1.0= almost perfect.

Conclusion: The referral information quality was modest, with considerable variation. There was a fair-substantial correlation between the TPS and the subjective quality assessed by VAS. Referral structure and appropriateness may contribute to explain some of the remaining discrepancy between the two assessments.

Disclosure of Interest: None declared

P1083 INCREASED PARTICIPATION IN COLORECTAL CANCER SCREENING DURING A PILOT OF A FAECAL IMMUNOCHEMICAL TEST FOR HAEMOGLOBIN (FIT) IN ENGLAND

S. Moss¹, C. Mathews¹, T. J. Day², S. Smith³, S. P. Halloran⁴⁵

¹Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, ²NHS Cancer Screening Programmes, Sheffield, ³NHS Bowel Cancer Screening Midlands and North West Programme Hub, Rugby, ⁴NHS Bowel Cancer Screening Southern Programme Hub, ⁵University of Surrey, Guildford, United Kingdom

Contact E-mail Address: s.moss@qmul.ac.uk

Introduction: The NHS Bowel Cancer Screening Programme (BCSP) in England has used a guaiac faecal occult blood test (gFOBt) since 2006. In April 2014 the BCSP commenced a six-month FIT Pilot study to assess the clinical, financial and organisational implications of adopting FIT.

Aims & Methods: Two regional BCSP Hubs (Southern and Midlands & North West) and associated Screening Centres participated in the pilot study. One in 28 invitees was offered FIT rather than gFOBt. 30,000 FIT invitations provided adequate power for analysis of FIT uptake compared with gFOBt. The OC-SENSOR FIT system (Eiken Chemical Co. Ltd., Japan) was used with a cut-off for positivity of 20 µg haemoglobin [Hb]/g faeces (100 ng Hb/mL buffer).

Results: 40,930 subjects were invited to participate with a FIT and 1,126,087 with a gFOBt during the pilot period (April - October 2014). Uptake of FIT was significantly higher than gFOBt (66.5% vs. 59.4%; OR 1.36). The increase in uptake was significantly greater for previous non-responders (FIT 25.8% vs. gFOBt 14.2%; OR 2.09), compared with subjects invited for the first time (61.2% vs. 50.3%; OR 1.56) and those who had participated previously (90.3% vs. 86.1%; OR 1.50). The increase in uptake was higher in males (FIT 64.6% vs. gFOBt 56.4%; OR 1.41) than females (68.3% vs. 62.1%; OR 1.31) and was apparent for all quintiles of deprivation. Of particular note is the increase in uptake with FIT compared with gFOBt in the most deprived and traditionally ‘hard-to-reach’ quintile (53.7% vs. 45.8%; OR 1.37).

Overall positivity was 7.8% with FIT (cut-off 20 µg Hb/g faeces) and 1.7% with gFOBt (OR 4.83). The increase in positivity was similar in males and females and in all deprivation quintiles, but increased with age. Significantly more colorectal cancers (CRC) (0.27% FIT vs. 0.12% gFOBt; OR 2.19) and advanced adenomas (1.74% vs. 0.35%; OR 4.97) were detected with FIT. The PPV for all neoplasms was significantly higher with FIT (55.9% vs. 51.9%; OR 1.17). At a cut-off of 150 µg Hb/g faeces (750 ng Hb/mL buffer), which yielded a positivity for FIT (1.8%) similar to gFOBt, FIT had a higher detection rate and PPV for advanced adenomas and all neoplasms.

Conclusion: FIT significantly increased uptake of screening and provides an opportunity to adjust the faecal Hb concentration cut-off for positivity and thus the burden on colonoscopy resource. Further analysis will determine how the faecal Hb concentration measured by FIT could be incorporated into a multivariate risk score for CRC.

Disclosure of Interest: None declared

P1084 TRIAL OF THE NEW BOWEL PREPARATION METHOD FOR CT COLONOGARAPHY

T. Tsuchida¹, M. Imai¹, Y. Yamada¹, M. Kubota¹, T. Okamoto¹, S. Haruki¹, T. Suzuki¹, K. Utano²

¹Cancer Screening Center, Cancer Institute Hospital, Tokyo, ²Fukushima Medical University Aizu Medical Center, Fukushima, Japan

Contact E-mail Address: tomohiro.tsuchida@jfcr.or.jp

Introduction: CT colonography (CTC) is a useful examination of colorectal cancer screening, and accuracy verification of CTC has been promoted in Japan. When performing the CTC, bowel preparation method is used similar method as colonoscopy. However, taking a large volume of bowel cleansing solution has contributed to reduce the acceptability of the examinee in colonoscopy.

Aims & Methods: We propose a new bowel preparation method to take a laxative and a water-soluble contrast agent without taking a large volume of bowel cleansing solution. Using this method, we evaluated the acceptability of the examinees and the accuracy of the CTC image. The subject of this examination was 30 examinees, including 16 men and 14 women with a mean age of 53.8 years old, who received CTC at the Cancer Screening Center of Cancer Institute Hospital. Examinee received a one capsule of laxative (Amitiza) and 50ml of water-soluble contrast agent (Gastrografin) on the night prior to CTC. Morning of CTC, examinee received 50ml of water-soluble contrast agent again. The day prior of CTC, all examinee were allowed a low-residue meal kit. For evaluation, the colon was divided into six segments (rectum to cecum). The observed amount of residual stool regardless of tagging was assessed on axial images using a 4-point scale: 0=no stool, 1=small stool, 2=moderate-size stool, and 3=large stool. The observed presence of residual fluid was assessed on axial images using a 4-point scale: 0=no fluid, 1=minimal fluid, 2=moderate fluid, and 3=substantial fluid. The homogeneity of fecal tagging was assessed using a 5-point scale: 0=no tagging, 1=poor tagging, 2=inhomogeneous tagging, 3=good tagging, and 4=excellent tagging. We performed an evaluation questionnaire of acceptability to examinees.

Results: The observed amount of residual stool was an average 0.5 points, the observed presence of residual fluid was an average 1.7 points, and the homogeneity of fecal tagging was an average 4.0 points. From the results of the questionnaire survey, it was 3 person answered “preparation was unacceptable", and there was small impact on the daily life and work.

Conclusion: The main advantage of this preparation method is that it is not necessary to take a large amount of bowel cleansing solution. Furthermore, preparation conditions are also excellent. Since acceptability of the examinees for this preparation method is generally good, it is expected to contribute to the popularization of CTC.

Disclosure of Interest: None declared

P1085  A MULTI DISCIPLINARY TEAM APPROACH FOR COMPLEX BENIGN COLO RECTAL POLYPS: A TERTIARY REFERRAL CENTRE EXPERIENCE

Z. P. Tsiamoulos¹, R. Rameshshanker¹, A. Rajendran¹, I. Beintaris¹, M. Garg¹, H. Spranger¹, M. Matharoo¹, A. Currie², R. Kennedy², O. Faiz², A. Antoniou², M. Moorghen³, J. Warusavitarne², A. Humphries¹, A. Haycock¹, A. Wilson¹, A. Latchford¹, N. Suzuki¹, A. Gupta⁴, S. Thomas-Gibson¹, B. P. Saunders¹

¹Wolfson Unit for Endoscopy, ²Department of Colorectal Surgery, ³Department of Histopathology, St Mark's Hospital/Academic Institute, ⁴Department of Radiology, St Mark's Hospital/Academic In, London, United Kingdom

Contact E-mail Address: ztsiamoulos@nhs.net

Introduction: Limited or no data is available on the impact of multidisciplinary team-(MDT) for complex benign colorectal polyps. Optimising the chance of successful and safe polyp resection at a single hospital visit is fundamental to offering a quality service.

Aims & Methods: A bi–weekly polyp MDT meeting was established in January 2013 to discuss the optimal management and resection strategies of all complex polyp referrals. The team comprises gastroenterologists/endoscopists, colorectal surgeons, pathologists, radiologists and a medical and nursing co-ordinator. The purpose of this pilot prospective study was to assess the impact of the MDT approach on the management of complex benign colorectal polyps.

Results: 96 polyp cases were discussed from January-2013 to October-2014. Inclusion criteria were defined as complex large polyps, those with difficult endoscopic access and recurrent fibrotic polyps after previous failed endoscopic excision. Most cases were tertiary referrals (78%). Reasons for referrals: very large complex polyps (55%)/difficult endoscopic access (54%)/previous unsuccessful polypectomy (36.4%). Majority of the polyps were in recto sigmoid (51%)/in caecal pole including ileocaecal valve or appendix (31.8%).

In 39.6% of cases the provisional management plan was changed after discussion at the polyp meeting. Apart from the conventional endoscopic techniques, the polyp MDT consensus proposed alternative approaches in 65% of cases to achieve a radical and complete excision of polyps. A single-hospital visit was recorded in 26% (25/96). The remaining cases (71/96) needed further diagnostic work-up and outpatient review (67/76), referral to the polyposis team (2/76), no polyp was found on two occasions.

Successful complete polyp removal was achieved in 85/96(88.5%) using conventional, novel and endo-surgical techniques; Endoscopic excision without surgical assistance in 39.6%(38/96), novel endo-surgical approaches in 25%(24/96 – Trans-Anal-Submucosal-Endoscopic-Resectio/TASER, Full-thickness-Laparo-endoscopic-EXcision/FLEX, Transanal-Endoscopic-Micro-Surgery/TEMS), laparoscopic-assisted-endoscopic-resection in 13.5%(13/96), surgical resection in 10.4%(10/96). Remaining 11 cases were managed as follows; surveillance in 4, no polyps found on examination of 2 cases, palliative care in one (carcinoma with metastases), 2 patients referred back to the base hospital for surgical resection, and one patient procedure is postponed due to co-morbidities and the other declined to have the procedure. 7 polyps were found to harbour carcinoma; all but one had surgical resection. The proposed MDT management plan was successfully followed in 82.3% of cases.

Conclusion: The polyp MDT provided a consensus on the key therapeutic issues for complex benign colorectal polyps and lead to a change in management plan in almost half of the patients. The multi-disciplinary approach helped to streamline patient care and avoid incomplete resection attempts.

Disclosure of Interest: None declared

TUESDAY, OCTOBER 27, 2015   09:00-17:00

OESOPHAGEAL, GASTRIC AND DUODENAL DISORDERS II – HALL 7__________

P1086 DIEULAFOY’S LESION CLINICAL AND EPIDEMIOLOGICAL ANALYSIS OF A RARE CAUSE OF GASTROINTESTINAL HEMORRAGE

D. M. Joao¹, N. Fernández¹, L. V. Ayala¹, L. Monteserin¹, P. Linares¹, J. L. Olcoz¹

¹Gastroenterology, Hospital Universitario de León, León, Spain

Contact E-mail Address: dianajoaomatias@gmail.com

Introduction: Dieulafoy’s lesion, defined as submucosal tortuous artery of wide caliber, is a rare cause of gastrointestinal bleeding. As it’s origen is an arterial bleeding, there is high risk of complications and morbimortality.

Aims & Methods

Aim: Analyze characteristics, risk factors, treatment and evolution associated to Dieulafoy s lesion.

Methods: Retrospective study since January 2000 and December 2013 of patients who underwent endoscopy resulting in Dieulafoy’s lesion diagnosis. we have evaluated epidemiological varies, clinical presentation, risk factors, treatment and clinical outcome.

Results: We gathered data from 77 patients, medium age 74 years, 52% males. Dieulafoy's lesion supposed 1.4% of gastrointestinal bleeding admitted at our centre in this period. The most frequent locations were gastric (57%), duodenal (30%) and colon (12%). The common clinical presentation was melena (38%), followed by hematemesis (34%) and rectorragy (10%). The medium haemoglobin levels at diagnosis were 8.2 g dl and average admission was 8.4 days. The most prevalent risk factors were hypertension (60%), cardiovascular disease (53%), diabetes mellitus (31%) and paroxysmal atrial fibrillation (26%). One third of the patients had history of antiplatelet use, 28% were under anticoagulants and less than a half of them used proton pump inhibitors (PPI) (46%).

40% of patients needed more than one endoscopy for diagnosis. The more common treatment was sclerosis hemoclip (39%), needing a second treatment in 26% of the cases. Moreover, 70% of the patients needed blood transfusion (average 3.26 units patient). The recurrence was 18%. 9/77 patients deceased (11.7%), all with history of upper GI bleeding.

According to location, the colon and duodenum lesion were higher among women and gastric among men (p < 0.05). Colon lesions were associated in higher proportion with coronary heart disease (p < 0.05). Duodenal lesions debuted with more anaemia (p < 0.05), more transfusional need (p < 0.01), more blood units per patient (p < 0.05) and greater recurrence (p < 0.05).

Conclusion: Dieulafoy's lesion, nevertheless its low incidence, presents important morbimortality, with high transfusion rate. It is associated with cardiovascular disease. The duodenal location es the one with greatest repercussion. Even though there were endoscopical advances, Dieulafoy's lesion is still a diagnostic and therapeutic challenge nowaday.

Disclosure of Interest: None declared

P1087 CLINICAL IMPACT OF USING RISK SCORING SYSTEMS IN PATIENTS WITH SUSPECTED UPPER GASTROINTESTINAL BLEEDING

E. Moreno Rincón¹, M. Muñoz García-Borruel¹, I. Pérez Medrano¹, C. Pedrajas Crespo¹, S. Chamorro Benítez¹, A. J. Hervás Molina¹, C. Gálvez Calderón¹, Á. González Galilea¹

¹Gastroenterology, University Hospital Reina Sofía, Córdoba, Spain

Contact E-mail Address: estefania.mr.86@gmail.com

Introduction: The clinical severity of an episode of upper gastrointestinal bleeding (UGIB) is highly variable. Numerous scoring systems have been developed to identify patients who have been affected adversely. Nevertheless, the use of these scoring systems in clinical practice is limited.

Aims & Methods: The aim of our study was to validate the application of different risk scoring systems in UGIB [Complete Rockall Score (CRS), clinical Rockall Score (RS), Glasgow-Blatchford Score (GBS) and modified Glasgow-Blatchford Score (mGBS)] within our country, and to compare in their utilities for prediction of clinical intervention and 30-day mortality. A retrospective and observational study was designed. 295 consecutive patients with acute UGIB admitted to a tertiary care hospital during a 1-year period were included. The primary outcome was the need for clinical intervention (blood transfusion, endoscopic, radiological or surgical intervention), and the secondary outcome included 30-day mortality. All of the above risk scoring systems were calculated for each enrolled patient. The validity of the tests was assessed using the receiver operated characteristics curve analysis (AUC), sensitivity, specificity, and positive and negative predictive values.

Results: The mean time until the requirement of upper endoscopy was of 12.76 ± 7.68 hours. 162 of the 295 patients (54.92 %) needed clinical intervention. 34 patients (11.53 %) developed recurrent bleeding and 30-day mortality was 5.08 % (UGIB-related mortality 3.73 %). The results in terms of sensitivity, specificity, and positive and negative predictive values for need for clinical intervention and 30-day mortality are shown in the table attached. The prognostic accuracy of GBS (AUC 0.849) and mGBS (AUC 0.854) were the highest achieved.

Conclusion: GBS and mGBS risk scoring systems are useful to select patients with low risk UGIB who could avoid hospitalisation. None of the scoring systems proved effective enough to predict mortality.

Abstract number P1087 Table.

Validation of scoring systems in predicting need for clinical intervention and 30-day mortality

1. Need for clinical intervention
Score*	Sensitivity(%)	Specificity (%)	Positive predictive value (%)	Negative predictive value (%)
RS > 0	95.68	36.09	64.58	100
CRS > 2	89.51	60.9	73.6	82.65
GBS > 0	100	2.26	55.48	100
mGBS > 0	100	3.01	55.67	100
1. 30-day mortality
Score*	Sensitivity(%)	Specificity(%)	Positive predictive value (%)	Negative predictive value (%)
RS > 0	93.33	19.29	5.83	98.18
CRS > 2	86.67	34.29	6.6	97.96
GBS > 0	100	1.07	5.14	100
mGBS > 0	100	1.43	5.15	100

*Scores cutoff for ‘high risk of intervention’: RS > 0; CRS > 2; GBS > 0; mGBS > 0.

Disclosure of Interest: None declared

P1088 COMPARISON OF AIMS65, GLASGOW-BLATCHFORD SCORE AND ROCKALL SCORE IN A EUROPEAN SERIES OF PATIENTS WITH UPPER GASTROINTESTINAL BLEEDING

E. Redondo-Cerezo¹, J. G. Martínez-Cara¹, R. Jiménez-Rosales¹, E. López-González¹, M. D. C. García-Marín¹, M. López de Hierro¹, J. de Teresa¹

¹Gastroenterology Department, University Hospital "Virgen de las Nieves". Granada. Spain, Granada, Spain

Contact E-mail Address: eredondoc@gmail.com

Introduction: AIMS65 is a recently developed score designed to predict in-hospital mortality, length of stay and costs of gastrointestinal bleeding.

Aims & Methods: Our aim was to revalidate AIMS65 score as predictor of inpatient and 6-months mortality in a southern European population. Our secondary objective was to compare the AIMS65 score’s performance with that of the GBS and RS with regard to mortality and the secondary outcomes of (A) a composite clinical endpoint of severity; (B) transfusion requirements; (C) rebleeding; (D) delayed mortality and (E) hospital length of stay. 309 patients with a diagnosis of upper gastrointestinal bleeding were included. AIMS65, Glasgow-Blatchford score and Rockall score were calculated to all of them. Every relevant clinical and biochemical data were collected, as well as transfusion requirements, endoscopic therapies, surgical or radiological treatments, and clinical outcomes for 6 months after admission. Clinical outcomes were in-hospital mortality, delayed mortality, rebleeding, composite endpoint, blood transfusion requirements, and hospital length of stay.

Results: Overall in-hospital mortality was 9.4%. On ROC analyses, AIMS65, GBS and RS were similar when predicting inpatient mortality (0.76 vs 0.78 vs 0.78). Regarding endoscopic intervention, AIMS65 and GBS were almost identical (0.62 vs. 0.62) but AIMS65 was useless when predicting rebleeding compared to GBS or AIMS65 scores (0.56 vs. 0.70 vs 0.71). The three scores proved to be very useful when predicting the need for blood transfusions. No patient with as AIMS65=0, GBS ≤ 6 or RS ≤ 4 died. When considering the composite endpoint of significant clinical outcomes, an AIMS65 score of 0 did not excluded patients which were considered high risk, but did a GBS ≤ 1 or RS ≤ 2. Considering the prediction of a prolonged in-hospital stay (>7 days), the three scores had similar AUROC. Delayed mortality was better predicted by AIMS65 than GBS or Rockall.

Table 1.

Score components

Age (years)	65	51-78
Albumin (g/dl)	3.1	2.7-3.7
International normalized ratio	1.48	1.1-1.5
Sistemic blood pressure	111	95-126
Pulse	90	75-102
Hemoglobin	9.7	7.8-11.6
Urea	81.31	44.5-94.5
Hematemesis	151	48.9%
Melena	223	72.2%
Hematochezia	25	8.1%
Mental status change	25	8.1%
Syncope	45	14.6%

Conclusion: AIMS65 is a good score for patients with upper gastrointestinal bleeding, especially in predicting inpatient and delayed mortality, selecting high-risk patients and the ones who need intervention, similar to what has been reported with the Glasgow-Blatchford and the Rockall score, but more applicable to daily practice.

Disclosure of Interest: None declared

P1089 COMPLICATIONS OF FOREGUT POLYPECTOMY: A PROSPECTIVE, LONGITUDINAL AND MULTICENTER STUDY

H. Cordova¹, L. Argüello², C. Loras³, A. Naranjo Rodríguez⁴, F. Riu Pons⁵, J. Gornals⁶, D. Nicolás⁷, L. Hernández Villalba⁸, S. Santolaria⁹, C. Leal¹⁰, C. Pons Vilardell¹¹, E. Pérez-Cuadrado Robles¹², O. García¹³, M. Papo¹⁴, J. L. Ulla Rocha¹⁵, N. Rojas¹, G. Fernández-Esparrach¹

¹Gastroenterology Department, Hospital Clinic, Barcelona, ²Gastroenterology Department, Hospital La Fe, Valencia, ³Gastroenterology Department, Hospital Mutua de Terrassa, Terrassa, ⁴Gastroenterology Department, Hospital Reina Sofía, Córdoba, ⁵Gastroenterology Department, Hospital del Mar, Barcelona, ⁶Gastroenterology Department, Hospital de Bellvitge, L'Hospitalet de Llobregat, ⁷Gastroenterology Department, Hospital de Canarias, Canarias, ⁸Gastroenterology Department, Hospital Santos Reyes, Aranda de Duero, ⁹Gastroenterology Department, Hospital San Jorge, Huesca, ¹⁰Gastroenterology Department, Hospital General de Vic, Vic, ¹¹Gastroenterology Department, Hospital de Viladecans, Viladecans, ¹²Gastroenterology Department, Hospital Morales Meseguer, Murcia, ¹³Gastroenterology Department, Hospital Moisès Broggi, Sant Joan Despi, ¹⁴Gastroenterology Department, Hospital Joan XXIII, Tarragona, ¹⁵Gastroenterology Department, Complejo Hospitalario de Pontevedra, Pontevedra, Spain

Contact E-mail Address: mgfernan@clinic.ub.es

Introduction: Gastric and duodenal polypectomy is a common technique but there is little information about potential complications. However, an increased risk of bleeding has been reported in retrospective series with small number of patients.

Aims & Methods: To prospectively evaluate the complications that occurred during consecutive gastric and duodenal polypectomies.

This is a multicenter, longitudinal and prospective study of all patients undergoing polypectomy of gastric or duodenal polyps ≥ 5 mm using a polypectomy snare. Patients with PT <50% and platelets <50,000 or clopidogrel in the 7 days prior to the polypectomy were excluded. Prophylactic measures of hemorrhage were allowed in certain predefined cases. Intraprocedural hemorrhage was defined as bleeding that lasts more than 30 seconds and severity was graded from 1 to 4. Late hemorrhage was defined as melena or hematochezia since discharge from endoscopy unit and up to 30 days. Patients were followed during 30 days with serial phone calls. Predictive factors of complications were analyzed.

Results: 310 patients were included. The indications for gastroscopy were iron deficiency anemia in 94 (30.3%), gastric polyps control in 73 (23.5%), dyspepsia/GERD in 49 (15.8%), GI bleeding in 35 (11.3%), dysphagia in 6 (1.9%), pernicious anemia in 6 (1.9%) and others in 46 (14.8%). A total of 287 (92.6%) polyps were located in the stomach and 23 (7.4%) polyps in the duodenum. Most lesions were polypoid (46.1% 0-Ip and 40.1% Is). Histopathological diagnosis was: 215 hyperplastic polyps (69.4%), 39 adenomas (12.6%), 23 fundic gland polyps (7.4%), and others 33 (10.6%). A total of 113 patients (36.5%) had antiplatelet/anticoagulant regimen. The mean size of polyps was 14.8 ± 8.7 mm and 69% were hyperplastic. We found 46 complications in 45 patients (14.5%): hemorrhage (n = 33, 73.3%), abdominal pain (n=10, 22.2%), perforation (n=1, 2.2%), aspiration pneumonitis (n=1, 2.2%), respiratory depression (n=1, 2.2%). Most complications occurred during the procedure (n=29, 64.4%). The severity of intraprocedural hemorrhage was grade 1 in 48.1%, grade 3 in 48.1 % and grade 4 in 3.7%. In 23 patients (69.7%) hemorrhage ocurred despite the use of prophylactic measures and in all cases hemostasis was achieved (15 with endoscopic treatment and 8 spontaneously). The only factor associated with bleeding was the type of polyp (hyperplastic 18/33 vs other types 197/277, p <0.04).

Conclusion: The incidence of foregut polypectomy complications is higher than reported in the colon. Hyperplastic polyps are at increased risk of bleeding and prophylactic measures do not reduce the risk.

Disclosure of Interest: None declared

P1090 AIMS65 SCORE IS A USEFUL PREDICTOR OF MORTALITY IN PATIENTS WITH NONVARICEAL UPPER GASTROINTESTINAL BLEEDING: URGENT ENDOSCOPY IN PATIENTS WITH HIGH AIMS65

H. S. Moon¹, J. S. Kim¹, S. H. Kang¹, J. K. Sung¹, H. Y. Jeong¹

¹Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea, Republic Of

Contact E-mail Address: mhs1357@cnuh.co.kr

Introduction: To validate the AIMS65 score for predicting mortality of patients with nonvariceal upper gastrointestinal bleeding and to evaluate the effectiveness of urgent (<8 h) endoscopic procedures in patients with high AIMS65 scores.

Aims & Methods: This was a 5-year single center, retrospective study. Nonvariceal, upper gastrointestinal bleeding was assessed using the AIM65 and Rockall scores. Scores were assessed under the receiver-operating characteristic curve (AUROC) for mortality. Patients with high AIMS65 scores (≥ 2) were allocated to either the urgent or non-urgent endoscopic procedure group. In-hospital mortality, success of endoscopic procedure, recurrence of bleeding, admission period and dose of transfusion were compared between the groups.

Results: A total of 634 patients were analyzed. The AIMS65 score successfully predicted mortality (AUROC = 0.943; 95% CI, 0.876-0.99) and was superior to the Rockall score (AUROC = 0.856, 95% CI, 0.743-0.969) in predicting mortality. The high AIMS65 scored group included 200 patients. The urgent endoscopic procedure group had reduced hospitalization periods (P < 0.05).

Conclusion: AIMS65 score may be useful in predicting mortality in nonvariceal upper gastrointestinal bleeding patients. Urgent endoscopic procedures in patients with high scores may be related to reduced hospitalization periods.

Disclosure of Interest: None declared

P1091 URGENT BEDSIDE ENDOSCOPY FOR NON-VARICEAL UPPER GASTROINTESTINAL BLEEDING IN INTENSIVE CARE UNITS

H.-S. Shin¹, H. Chung¹, J. C. Park¹, S. K. Shin¹, S. K. Lee¹, Y. C. Lee¹

¹Department of Internal Medicine, Yonsei University Severance Hospital, Seoul, Korea, Republic Of

Contact E-mail Address: NYOSUN84@yuhs.ac

Introduction: Urgent bedside esophagogastroduodenoscopy (EGD) for upper gastrointestinal bleeding (UGIB) in the intensive care unit (ICU) is essential for prompt identification and hemostasis of the source of hemorrhage. However, the clinical characteristics and outcomes of endoscopic hemostasis have not been well studied.

Aims & Methods: The aim of this study was to investigate clinical characteristics of hemorrhage and outcomes of endoscopic hemostasis in patients with non-variceal UGIB (NVUGIB) after admission to the ICU.

A total of 62 ICU patients (ICU group) and 288 non-ICU patients (non-ICU group) with NVUGIB who underwent urgent EGD in Yonsei University Severance Hospital from January 2010 to April 2014 were included. We compared the demographics, clinical characteristics, technical success rate for endoscopic hemostasis, rate of rebleeding and mortality between two groups.

Results: The mean ages were 66.1 and 64.1 years (p = ns) and the number of comorbidities were 2.65 and 1.61 (p < 0.05) in ICU group and non-ICU group, respectively.

The most common initial clinical presentations were acute drop in hemoglobin level in ICU group (23/62, 37.1%) and melena in non-ICU group (180/288, 62.5%). ICU group presented higher blood urea nitrogen level (47.1 vs. 35.4 mg/dL), lower serum albumin level (2.5 vs. 3.2 g/dL), and higher Rockall score (7.01 vs. 5.37) with statistical significance.

The most common endoscopic finding was gastric ulcer with oozing hemorrhage (Forrest Ib) in both groups and initial technical success rates for endoscopic hemostasis were similar (91.5% vs. 94.6%, p = ns).

However, ICU group was significantly associated with higher 7-day rebleeding rate (37.1% vs. 10.4%, p < 0.05), shorter mean interval for rebleeding (1.4 vs. 3.4 days, p < 0.05), higher 30-day mortality rate (54.8% vs. 2.1%, p < 0.05), and higher bleeding-related mortality rate (16.1% vs. 1.4%, p < 0.05).

Conclusion: Despite similar technical success rate of endoscopic hemostasis, recurrent bleeding rate and bleeding-related mortality rate were significantly higher and interval for rebleeding was shorter in ICU patients. To reduce rebleeding rate and bleeding-related mortality rate, close monitoring and preemptive second-look endoscopic surveillance within 24 hours may be beneficial in the ICU setting.

Disclosure of Interest: None declared

P1092 THE MANCHESTER TRIAGE SYSTEM (MTS): A SCORE FOR EMERGENCY MANAGEMENT OF PATIENTS WITH ACUTE GASTROINTESTINAL BLEEDING

J. W. Rey¹, S. Dümcke²³, A. Fischbach⁴, M. Dieroff⁴, D. Teubner¹, A. Tresch²³, M. Nguyen-Tat⁵, J. U. Marquardt⁵, H. Manner¹, R. Kiesslich¹, A. Hoffman¹

¹Department of Internal Medicine II, HSK Clinic, Wiesbaden, ²Max Planck Institute for Plant Breeding Research, ³Biocenter for Genetic, University of Cologne, Cologne, ⁴Department of Emergency, HSK Clinic, Wiesbaden, ⁵First Department of Internal Medicine, University Medical Center, Mainz, Germany

Contact E-mail Address: johannes.wilhelm.rey@t-online.de

Introduction: Suspicion of gastrointestinal bleeding (GIBLEED) is a prevalent diagnosis in emergency departments. Despite existing gastroenterological and endoscopic scores to estimate the risk of GIBLEED, the primary clinical assessment remains challenging for both, emergency doctors and interventional gastroenterologists. The five step Manchester Triage System (MTS) is an easy to use and validated score that is often applied for the initial assessment of patient in emergency rooms (ER). The MTS classifies patients into five priority levels, ranging from level 1 (emergency, should receive immediate medical attention) to levels 2-5, corresponding to a suggested medical evaluation within 10, 30, 60, and 120 minutes, respectively. The MTS was established to manage clinical risk of administrating medical attention. The aim of our retrospective analyse was, to determine if the MTS correlates with presence of a GIBLEED.

Aims & Methods: All patients who were admitted between January 2014 and December 2014 to our emergency department in a maximum care hospital (HSK Clinic Wiesbaden) were retrospectively analyzed. All relevant computer-based clinical patient records that included MTS priority levels were evaluated and associated with endoscopic findings.

Results: In summary 5689 gastroenterologic emergencies were treated at our emergency room. 284 patients (4.9%) (Mean age 64.3 years) were under suspicion of having GIBLEED. 47.5% of these patients were introduced to the emergency service. among these, 162 patients (57.04%) were admitted for immediate treatment. 160 patients (56.3%) received endoscopic diagnostic. 33.1% of patients who were transferred to the endoscopy by the emergency service team showed a confirmed endoscopic diagnosis of GIBLEED, compared to 49.1% who were self-referring to the ER (p = 0.007). Endoscopic intervention for hemostasis was needed in 22 patients (13.8%). The success rate of hemostasis was 96.6%. While 61.2% of all patients assigned to MTS levels 1, 2, and 3 received endoscopy, endoscopy rates in patients of levels 4 and 5 were only 26.3% (p < 0.01). Gastrointestinal bleeding was endoscopically confirmed in 40% of patients with level 1 to 2, 34% in level 3 and 5.3% level 4 to 5, which shows a significant correlation of MTS score and GIBLEED (p = 0.043, χ² test).

Conclusion: The MTS is an appropriate way to estimate the likelihood of GIBLEED for patients presenting in emergency departments. Patients at levels 1-3 should receive immediate endoscopic work up. Elective endoscopy can be performed in patients classified with levels 4-5.

Disclosure of Interest: None declared

P1093 THE USE OF CAPSULE ENDOSCOPY IN TRIAGING PATIENTS WITH UPPER GASTROINTESTINAL BLEEDING: A RANDOMISED STUDY

J. J. Y. Sung¹, R. S. Y. Tang¹, J. Y. L. Ching¹, J. Y. W. Lau¹, T. Rainer²

¹Institute of Digestive Disease, ²Department of Accident and Emergency Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong , China

Contact E-mail Address: jjysung@cuhk.edu.hk

Introduction: Patients presented to hospitals with coffee ground vomiting or black-color stool may not be actually suffering from active upper gastrointestinal bleeding (UGIB). Hospital admission can be avoided if active UGIB or high-risk lesions are excluded at the emergency room (ER).

Aims & Methods: This is a prospective randomized study comparing the use of capsule endoscopy as a triage tool versus standard care in the management of UGIB at the ER of an acute hospital. Patients presented to the ER at an acute hospital with symptoms suggestive of UGIB were recruited into this study. Vital signs (blood pressure, pulse, conscious state), complete blood count and serum chemistry were monitored at the ER. Patients who were not in hemodynamic shock, coma or actively vomiting blood were randomized to receive either capsule endoscopy (CE) by using PILLCam ESO (GIVEN) or (ST) standard care of hospitalization and early endoscopy within 24 hours. Patients in the CE group with capsule video showing clean stomach (no fresh blood or coffee ground) and no signs of active bleeding or high-risk lesions were discharged home and followed by out-patient endoscopy within 3 days. CE patients showing the following signs : 1. >5 ml coffee ground or fresh blood in stomach; 2. active oozing or spurting blood from upper gastrointestinal tract; 3. visible vessel or blood clot at ulcer base; 4. esophageal or gastric varices with red wale sign or fibrin clot, would be admitted for endoscopy within 24 hours. Patients in the ST group were admitted to hospital for resuscitation, observation and endoscopy within 24 hours.

Results: 71 patients were recruited and randomized to CE (n=37) or ST (n=34). Three patients in CE group were excluded because of known history of variceal bleeding (1x), retained capsule in esophagus (1x) and fever which precluded early endoscopy (1x). There were 34 patients in both CE and ST groups for analysis. The basic demography, blood pressure and pulse rate, baseline blood count and chemistry of the CE and ST groups were comparable. 7 patients in CE group were considered high-risk and hence required admission, whereas all 34 in ST group were admitted. Among the 7 CE patients (20.6%) admitted, 3 were confirmed to have high-risk lesions or active bleeding (GV/EV 1x; GIST with coffee ground 1x; GU with fresh blood 1x). None of the 27 CE patients discharged home were subsequently found to have active bleeding, except one found to have GU with visible vessel. None of the patients in both CE and ST group had early recurrent bleeding or died.

Conclusion: Capsule endoscopy can select most of the high-risk patient presenting with coffee group vomiting or melena for hospital admission and urgent endoscopy. Capsule endoscopy is a feasible and safe triage method in the management of UGIB.

Disclosure of Interest: None declared

P1094 CHRONIC ANAEMIA DUE TO GASTROINTESTINAL BLEEDING, WHEN DO GASTROENTEROLOGISTS TRANSFUSE? A NATIONWIDE SURVEY IN THE NETHERLANDS

K. Grooteman¹, E. van Geenen¹, J. Drenth¹

¹Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, Netherlands

Contact E-mail Address: karina.grooteman@radboudumc.nl

Introduction: Transfusion strategies have become more restricted over the past decade. Most guidelines state that in patients with chronic anaemia, symptoms are the most essential trigger to transfuse. This might differ for acute gastrointestinal bleeding, where prophylactic transfusions might be necessary at an earlier stage. Our hypothesis is that decision-making for transfusion among gastroenterologists varies considerably.

Aims & Methods: Our aim was to identify preferences and predictors of transfusion decision-making in chronic anaemia due to gastrointestinal bleeding.

To achieve this aim, a computerized adaptive choice-based conjoint survey was administered between February and April of 2015 to gastroenterologists in the Netherlands. The survey quantified the relative importance of 7 patient attributes, including haemoglobin levels, haemoglobin stability, age, iron indices, the presence of anaemia related symptoms, cardiovascular comorbidities and the number of transfusions in the past half year. Triggers of transfusion were studied in a scenario of chronic anaemia due to bleeding from angiodysplasias.

Results: A total of 112 gastroenterologists completed the survey (response rate = 28%; mean age = 47 years; 24% women). Of 7 attributes assessed, absolute haemoglobin level was the most important incentive of transfusions, accounting for 42% of decision-making, followed by age (15%), haemoglobin stability (12%), anaemia related symptoms (10%), cardiovascular comorbidities (10%), the number of transfusions in the past half year (6%) and iron indices (5%). An inflection point was found at a haemoglobin level of 8.0 g/dL, above this value gastroenterologists would not prescribe a transfusion. The average part-worth utilities for the different haemoglobin levels (>9.5 g/dL, 8.0-9.5 g/dL, 6.4-7.9 g/dL, <6.4 g/dL) were respectively -161 (SD 23), -27 (SD 19), 55 (SD 20), and 133 (SD 23).

Conclusion: Independent of all other factors, absolute haemoglobin level was found as the most important clinical factor to transfusion decision-making. In contrast, the presence of anaemia related symptoms and iron indices was of relatively little importance. This contradicts the current Dutch transfusion guideline.

Disclosure of Interest: None declared

P1095 DIAGNOSIS OF CHRONIC ATROPHIC GASTRITIS IN PRIMARY CARE SETTING BY MEANS OF GASTROPANEL®: A POPULATION STUDY ON 10,000 CONSECUTIVE PATIENTS

F. Di Mario¹, E. Goni¹, M. Franceschi², G. Baldassarre², R. Cannizzaro³, N. Dal Bo'⁴, V. Corrente⁵, A. Bertelè⁶, M. Venerito⁷, P. Malfertheiner⁷, C. Scarpignato¹, M. Rugge⁸

¹Department of Clinical and Experimental Medicine, University of Parma, Parma, ²Endoscopic Unit - Department of Surgery , ULSS 4 AltoVicentino, Santorso (VI), ³Gastroenterology Unit, Centro di Riferimento Oncologico (CRO), Aviano National Cancer Institute, Aviano, ⁴Gastroenterology and Gastrointestinal Endoscopy Unit, Treviso Hospital, Treviso, ⁵Internal Medicine and Critical Subacute Care Unit, ⁶Department of Clinical and Experimental Medicine, Parma University Hospital, Parma, Italy, ⁷Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany, ⁸Department of Pathology, University of Padua, Padova, Italy

Contact E-mail Address: elisabetta.goni@gmail.com

Introduction: Chronic atrophic gastritis (CAG) is a stomach precancerous condition, often related to Helicobacter pylori (H.p.) infection. This condition is characterized by hypo- or achloridria due to loss of appropriate gastric glands. Gastropanel^® is a non-invasive test able to detect both CAG and H.p. infection. This test, which provides information on both morphological and functional status of the gastric mucosa, is often referred to as “serological biopsy”.

Aims & Methods

Aim: The aim of the present study is to investigate, by means of Gastropanel^®, the prevalence of CAG in a large primary care population.

Subjects and Methods: Ten thousand dyspeptic patients, from two different areas of North-East of Italy, were enrolled. The first one (Group A) included 7,400 patients (M:F=1.2:2.0 mean age 53 years) from 2003 to 2014 while the second one (Group B) involved 2,600 patients (M:F=1.5:2.3, mean age 56 years) from 2011 to 2013. Upper GI endoscopy with biopsies sampling, evaluated histologically according to the Sydney classification and the O.L.G.A. staging system, as well as Gastropanel^® (Biohit Oyj, Helsinki, Finland) were performed in every patient.

Serological diagnosis of CAG was made when PGI serum levels were < 25 microg/L and G-17 concentrations > 14 pmol/L. Histological diagnosis of CAG followed the criteria of both Sydney system and O.L.G.A. staging.

Results: Overall, CAG was diagnosed by serology in 716 out of 10,000 patients. In Group A population, 608 patients (mean age 57 years old) has a CAG, 2,492 (mean age 54) a non-atrophic gastritis related with H.p. infection was performed while 879 patients (mean age 44 years) presented with a normal gastric morpho-functional assessment. In Group B population, CAG was found in 108 patients (mean age 58 years) and H.p.-related gastritis in 643 (mean age 59) while a normal pattern was detected in 721 patients (mean age 47).

Conclusion: Overall, in a primary care setting, a picture of CAG was found in 7.2% of patients. The prevalence was higher in Group A than in Group B (8.2% and 4.2%, respectively) for unknown reasons. The mean age of subjects with CAG was higher than that of patients with NAG H.p-related and normal population in both areas.

These findings suggest that CAG is more prevalent than previously thought and confirm that Gastropanel^® is an effective non invasive tool for the screening of this precancerous condition.

Disclosure of Interest: None declared

P1096 ESTABLISHING A PROMPT ENDOSCOPY PROGRAMME FOR PATIENTS WITH DYSPEPSIA AND ALARM FEATURES REDUCES THE NUMBER OF SECONDARY CARE CONSULTATIONS

F. J. Garcia-Alonso¹, D. Bonillo-Cambrodón¹, M. Hernández Tejero¹, A. Bermejo¹, A. Algaba¹, A. Guardiola¹, P. Valer¹, I. Guerra¹, F. Bermejo¹

¹Gastroenterology, Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain

Contact E-mail Address: fj.garcia.alonso@gmail.com

Introduction: Dyspepsia is commonly encountered by primary care providers (PCP) and motives a significant number of endoscopies and secondary care consultations. A guideline issued by both the Spanish Society of Gastroenterology and the Spanish Society of Primary Care recommends prompt endoscopy in subjects with alarm features (anaemia, weight loss, dysphagia, gastrointestinal bleeding or abdominal findings) or appearance of symptoms after 55 years of age. We present the development of a prompt endoscopy programme (PEP) for dyspepsia with alarm features in primary care.

Aims & Methods: In June 2013 a PEP for patients with dyspepsia and alarm features was created with the cooperation of a primary care clinic (PCC) attending 36577 people, with a median of 58 monthly new gastroenterological secondary care consultations. After data analysis in August 2014, the programme was made available to all PCCs related to our hospital, which attends roughly 225000 people.

Demographic, clinical, endoscopic and histological data were prospectively retrieved, as well as secondary care consultations after endoscopy. A satisfaction survey was undertaken in the PCC participating in the pilot programme. Proper indication of prompt endoscopy was defined in the presence of at least one red flag or age >55. Significant findings were defined as cancer, ulcers or severe esophagitis.

Results: In the pilot study 113 patients were included with a median age of 57.4 (IQR: 45.9-64.1), 61.1% of them were women. Symptoms had been present for a median 4.5 months (2.5-12.5). 84.2% (95% CI: 75.8-92.6%) of endoscopies had been properly indicated. Monthly secondary care consultations from the PCC during the pilot study period compared with previous years were reduced in 10.5 patients (5.6-15.5).

Including all subjects attended, a total of 296 patients have undergone endoscopy with a median age of 56.3 (45.4-64.4), 61.5% were women. Proper indications were made in 81.8% (77.3-86.2%) of patients. Most common alarm features were: age over 55 (55.7%), weight loss (25.5%) and anaemia (20.8%). 38.9% presented 2 or more red flags. Upper epigastric pain (72.8%) was the most common symptom, but 50% also fulfilled criteria of gastroesophageal reflux disease, which was more frequent than bloating (40.9%) and early satiety (31.6%).

Significant findings were encountered in 14.5% (11-19%); gastroesophageal cancer in 1% (3 gastric cancers), peptic ulcers in 11.1% and severe esophagitis in 2.7%. Other cancers were found during a 2 months follow-up in 1% (colon adenocarcinoma, metastatic cancer of unknown origin and multiple myeloma). H pylori was diagnosed in 38.9% and a normal endoscopic appearance was present in 30.5%. The positive and negative predictive values of alarm features were 17.4% (12.8-22.7%) and 98.1% (90.1-100%) respectively 17.6% of patients were submitted to the gastroenterology out-patient clinic.

The satisfaction survey was completed by 24 PCP. All of them considered the PEP useful for their daily practice, although only 66.7% had used it. Most non users (87.5%) referred having met no patients with alarm features.

Conclusion: Availability of prompt endoscopy for dyspepsia with alarm features is considered a valuable asset by PCP and reduces the number of secondary care consultations.

Disclosure of Interest: None declared

P1097 PREVALENCE AND SOCIO-DEMOGRAPHIC DETERMINANTS OF UNINVESTIGATED DYSPEPSIA IN THE CZECH REPUBLIC

S. Rejchrt¹, I. Koupil², M. Kopacova¹, M. Skodova Fendrichova¹, B. Seifert³, V. Vorisek⁴, J. Spirkova⁴, T. Douda¹, J. Bures¹, I. Tacheci¹

¹2nd Department of Internal Medicine – Gastroenterology, Charles University Faculty of Medicine & University Teaching Hospital, Hradec Kralove, Czech Republic, ²Centre for Health Equity Studies, Stockholm University/Karolinska Institute, Stockholm, Sweden, ³Institute of General Practice, First Faculty of Medicine, Charles University, Prague, ⁴Institute of Clinical Biochemistry and Diagnostics, Charles University Faculty of Medicine & University Teaching Hospital, Hradec Kralove, Czech Republic

Contact E-mail Address: rejchrt@lfhk.cuni.cz

Introduction: Epidemiology of uninvestigated dyspepsia was studied in the Czech Republic for the first time in 2001 (1). The aim this current multi-centre prospective study was to evaluate dyspepsia using the same methods in a representative sample of general unselected population from the same geographical areas 10 years later.

Aims & Methods: A total of 22 centres entered the study. They were spread over the whole country, corresponding well to the geographical distribution of the Czech population. A total of 1,836 subjects (863 males and 973 females; aged 5-98 years) took part in the study and responded to the question on prevalence of dyspepsia. Complete data on variables used in our analysis was available for 1,685 subjects. The proportion of subjects reporting dyspepsia did not differ significantly between the restricted sample and the group excluded from multivariable analyses. Helicobacter pylori (Hp) status was investigated in all subject by means of 13C-urea breath test.

Results: In subjects aged 5-24 years, when we analyzed determinants of dyspepsia by type (subgroup A: dyspepsia as the only long-lasting symptom vs. subgroup B: dyspepsia as a part of the complex of other complaints or previously recognized diseases), we noted somewhat stronger increase in risk of dyspepsia A with age (OR 1.15 per 1 year of age, 95% CI 1.05-1.26, adjusted for gender) and with current use of antibiotics (OR 3.23 in users vs. non-users, 95% CI 0.87-11.9). In subjects aged 25+ years, when analyzed by type of dyspepsia, a statistically significant negative association of age with dyspepsia of type A became apparent (OR 0.95 per 1 year of age, 95% CI 0.94-0.97) while the association between age and dyspepsia type B was also statistically significant albeit positive (OR 1.02 per 1 year of age, 95% CI 1.01, 1.04). Furthermore, subjects who were single were at lower risk of dyspepsia type B (OR 0.46 in single vs. married, 95% CI 0.21-0.99, adjusted for age and gender). The unexpected protective effect of elementary education appeared also to be stronger for dyspepsia type B (OR for elementary vs. university educated 0.25, 95% CI 0.07-0.86, adjusted for age and gender). Hp negative subjects reported dyspepsia in 4.1% (aged 5-24 years) and 18.1 % (aged 25+ years). In Hp positive subjects, dyspepsia was present in 7.1% (aged 5-24 years; OR 1.45, 95% CI 0.41, 5.16) and 16.3% (aged 25+ years; OR 0.85, 95% CI 0.60, 1.21, adjusted for gender and age).

Conclusion: Despite the substantial decrease of Hp infection in the Czech Republic over the past 10 years, the prevalence and basic socio-demographic determinants of uninvestigated dyspepsia did not change significantly.

Disclosure of Interest: None declared

P1098 IN VITRO EFFECT OF LEVOSULPIRIDE ON THE MAIN CONTRACTILITY PATTERNS IN THE HUMAN JEJUNUM, GASTRIC ANTRUM AND FUNDUS

D. Gallego¹, O. Ortega², C. Arenas¹, I. López², E. Mans², P. Clave²³

¹Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III (ISCIII), Barcelona, ²Gastrointestinal Physiology Laboratory, Department of Surgery, Hospital de Mataró and CIBERehd, Mataro, ³Health Sciences Research Institute, Germans Trias i Pujol Foundation, Barcelona, Spain

Contact E-mail Address: pere.clave@ciberehd.org

Introduction: To assess the effect of drugs currently in use to ameliorate symptoms of functional dyspepsia and gastroparesis in human tissue it is important to evaluate their mechanism of action on isolated human samples. Therefore, the aim of the present study was to evaluate the effect of the prokinetic drug levosulpiride on the main in vitro contractility patterns of the human stomach and jejunum.

Aims & Methods: Circular muscle strips from stomach (antrum and fundus) and jejunum from patients undergoing bariatric surgery were studied using organ baths to evaluate: the effect of levosulpiride on the spontaneous contractility and on electrical field stimulation (EFS)-induced release of neurotransmitters from enteric motor neurons.

Results: Levosulpiride, a 5HT₄ agonist/D₂ antagonist, caused an increase in the EFS-induced cholinergic contractions, in the gastric antrum (37 ± 15.18% of increase at 100μM, pEC₅₀=4.46 ± 0.14; p < 0.05, n=8) and jejunum (45.4 ± 22.03% of increase at 100μM, pEC₅₀=3.78 ± 6.81; p < 0.05 n=5), whereas it did not cause a significant increase in the gastric fundus. It also caused a slight tone decrease and frequency of the spontaneous contractions increase in the jejunum whereas it did not have any major effect on the spontaneous contractility in the stomach. It did not have any effect on EFS-induced relaxations caused mainly by nitric oxide (NO) in the stomach (antrum and fundus) and by NO and ATP in the jejunum.

Conclusion: Our results suggest that the prokinetic effects of levosulpiride are mainly due to facilitating the release of acetylcholine by enteric motor neurons in the gastric antrum and the jejunum.

Disclosure of Interest: D. Gallego Financial support for research: Laboratorios Salvat S. A., O. Ortega Financial support for research: Laboratorios Salvat S. A., C. Arenas Financial support for research: Laboratorios Salvat S. A., I. López Financial support for research: Laboratorios Salvat S. A., E. Mans Financial support for research: Laboratorios Salvat S. A., P. Clave Financial support for research: Laboratorios Salvat S. A.

P1099 AN HERBAL MEDICINE FOR THE SYMPTOMATIC RELIEF OF MILD GASTROINTESTINAL DISCOMFORT, ALTHAEA ROOT EXTRACT, HAS PROTECTIVE EFFECTS ON HUMAN MUCOSA CELLS

F. J. Zippel¹, N. Hellenbrand¹, C. Fink², O. Kelber², H. Abdel-Aziz², A. Hensel¹

¹Institute of Pharmaceutical Biology and Phytochemistry, University of Muenster, Münster, ²Scientific Department, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany

Contact E-mail Address: olaf.kelber@bayer.com

Introduction: The use of herbal medicinal products in gastrointestinal complaints is very common in Europe. To these belongs the extract of the root of the herb Althea officinalis L. (marshmallow root), which is traditionally used "for the symptomatic relief of mild gastrointestinal discomfort", an indication which has been confirmed by the European drug regulatory agency EMA [1], besides its more common use in the treatment of pharyngeal irritation and associated dry cough. As this use has been often rated as being merely symptomatic [1], a study has been conducted with the aim to identify mechanisms of action which point to an active, causal therapeutic effect in mucosal cells, beside its well-characterized protective physical effect [2].

Aims & Methods: Therefore the mechanisms of action of a well defined extract of Althea officinalis roots, STW 42, and of polysaccharides from the extract (RPS) were tested in a human mucosal cell line (KB-cells, origin: nasopharynx), and for comparison purposes, a human fibroblast cell line [3, 4].

Results: In KB-cells, RPS (1-10 µg/mL) significantly increased cell vitality, measured as reduction of the tetrazolium salt WST-1, in contrast, STW 42 had no significant effect at that time. Cellular proliferation, measured by ELISA in the BrdU-Test was significantly stimulated by STW 42 (10 µg/L), while RPS had this effect only at 100 µg/mL. RPS, labelled by fluorescein 5-isothiocyanat (FITC), was internalised by KB-cells, not fibroblasts, after incubation for 14 h.

Conclusion: According to these results, STW 42 may have an active influence on mucosal cells and fibroblasts. Althaea polysaccharides can even be internalised by mucosal cells. This points to a not merely demulcent, but actively protective effect on the mucosa. By stimulating mucosal regeneration, it potentially could even have a causal therapeutic effect in mucosal disturbances.

Disclosure of Interest: F. Zippel: None declared, N. Hellenbrand: None declared, C. Fink Financial support for research: Employee, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany, O. Kelber Financial support for research: Employee, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany, H. Abdel-Aziz Financial support for research: Employee, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany, A. Hensel Financial support for research: Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany

P1100 STRUCTURAL CHANGES OF ENTERIC GLIAL CELLS AND MOTILITY DISORDERS OF THE STOMACH AS RESPONSES TO EARLY LIFE STRESS (MATERNAL SEPARATION) AND ACUTE STRESS IN ADULTHOOD IN RATS

K. Tominaga¹, Y. Fujikawa¹, T. Tanigawa¹, T. Watanabe¹, Y. Fujiwara¹, T. Arakawa¹

¹Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan

Contact E-mail Address: tomy@med.osaka-cu.ac.jp

Introduction: Enteric glial cells (EGCs) play an important role in physiological neurotransmission. However, its regulatory mechanism(s) under various stresses (mental, physical, acute, and/or chronic) remains to be elucidated. We investigated changes in mRNA expression and structural changes in gastric EGCs in the time course of the stress intensity in a maternal separation (MS) model, a model of early life stress affecting central glial cells.

Aims & Methods: Male Wistar rat pups underwent MS for 3 hours starting on postnatal days 2-14. At 8 weeks of age, we used the water immersion method as an acute stress (AS) model and excised the whole stomach at 24 hours later. For the AS, MS, MS + AS, and control groups, we evaluated mRNA expressions of glial fibrillary acid protein (GFAP) using real time RT-RCR. Whole mount longitudinal muscle-myenteric plexus preparations were used for immunohistochemistry of EGCs (GFAP) with pan neuronal marker (HuC/D). We evaluated gastric emptying time using the phenol red method.

Results: GFAP mRNA expression was increased by 2-fold at 1 hour after AS compared to the controls (p < 0.05). However, in the MS + AS group, AS did not affect GFAP mRNA expression. The two-dimensional area with apparent overlap of these EGC processes with the neurons was expressed as a percentage of the area encompassing the HuC/D-positive neurons. The area ratio significantly increased according to the stress intensity (10.2%, acute stress; 10.0%, maternal separation; 26.4%, maternal separation with acute stress vs. 5.1%, control). The density of GFAP-positive EGC processes that apparently overlapped with the neurons and the extent of bulbous swelling of terminals increased according to the stress intensity. Two types of glial processes were observed: filamentous (no obvious neck or bulbous terminal swelling) and leaf-like (a neck region with a bulbous terminal swelling). Mean ratio of leaf-like processes to total processes per ganglion was 4% in the control group, which was increased to 17% by AS for 8 hours. The mean ratio was 13% in the MS group, and began to increase from 1 hour in a time dependent manner in the MS + AS group and reached up to 25% at 8 hours. In the MS group, gastric emptying was significantly delayed compared with those in control group in addition to aging. At 17 weeks, MS with AS induced the significant delay in gastric emptying.

Conclusion: Maternal separation with additional acute stress in adulthood caused structural changes in gastric EGCs, which may be critically important for glio-neural dysfunction of functional gastrointestinal diseases.

Disclosure of Interest: None declared

P1101 FUNCTIONAL DYSPEPSIA IS SUSCEPTIBLE TO CD14, GNB3, TRPV1 -BUT NOT MIF- GENE POLYMORPHISMS IN A WESTERN POPULATION

K. Triantafyllou¹, A. Kourikou¹, M. Gazouli¹, G. P. Karamanolis¹, G. D. Dimitriadis¹

¹Medical School, Athens University, Athens, Greece

Contact E-mail Address: ktriant@med.uoa.gr

Introduction: Functional dyspepsia (FD) might be susceptible to gene polymorphisms related to inflammation (CD14, MIF), motor (GNB3) and sensory dysfunction (TRPV1). Association studies have shown diverse results among different populations. Herein, we present the final results of our association study in a Western population; preliminary results were presented at UEGW 2012¹.

Aims & Methods: We aimed to examine the association between CD14, GNB3, MIF and TRPV1 gene polymorphisms and FD (Rome III criteria). We studied gene polymorphisms using polymerase chain reaction-based methods and we measured disease symptoms burden with a modified GSRS scale.

Results: We studied 100 dyspeptic (62 with epigastric pain syndrome; 41% H. pylori positive) and 119 healthy individuals. The frequencies of the TT genotype and T allele of the CD14 polymorphism were significantly associated (OR [95%CI], p) with FD (2.4 [1.16-5.01], 0.02 and 1.55 [1.05-2.28], p =  0.03, respectively). TT genotype and T allele frequencies of GNB3 showed also significant association with FD (4.73 [1.25-17.83], 0.02 and 2.14 [1.27-3.61], 0.006, respectively). While the distribution of GG, GC and CC MIF gene genotypes was similar between controls and FD patients, GC TRPV1 genotype and C TRPV1 allele were more common in controls (p = 0.06) and in FD patients (p = 0.07), respectively. Among dyspeptics, CD14 TT genotype was related to significantly lower epigastric pain burden score compared to the CC and CT genotypes (3.72 ± 0.18 vs. 4.36 ± 0.11 and 4.17 ± 0.12, p = 0.012). Similarly, the presence of CD14 T allele was related to lower epigastric pain burden score compared to the C allele (3.98 ± 0.1 vs. 4.36 ± 0.11, p = 0.012).

Conclusion: FD is susceptible to CD14, GNB3 and TRPV1 gene polymorphisms while CD14 gene polymorphisms are also associated with epigastric pain burden in our Western population.

Disclosure of Interest: K. Triantafyllou Financial support for research: Takeda, MSD, Salix, Angelini, Lecture fee(s): AstraZeneka, AbbVie, Takeda, A. Kourikou: None declared, M. Gazouli: None declared, G. Karamanolis: None declared, G. Dimitriadis: None declared

P1102 ASPARTIC ACID IS EFFECTIVE FOR EARLY SATIETY (FUNCTIONAL DYSPEPSIA): EFFECTS OF AMINO ACIDS ON THE GASTRIC EMPTYING EVALUATED BY BREATH TEST AND THE GASTRIC ADAPTIVE RELAXATION EVALUATED BY BAROSTAT IN RATS

M. Uchida¹, C. Iwamoto¹, O. Kobayashi¹

¹R&D Division, Food Science Research Laboratories, Meiji Co., Ltd., Odawara, Japan

Contact E-mail Address: masayuki.uchida@meiji.com

Introduction: Amino acid has been reported to have many physiological functions. Glutamic acid enhances contraction of the antrum and tryptophan inhibits gastric emptying. However, the effects of the other amino acid have not been clarified on the gastric function. On the other hand, Sanaka et al. (Dig Dis Sci. 2010) reported that PPI therapy enhanced the gastric adaptive relaxation and inhibited the gastric emptying, suggesting the relationship between gastric adaptive relaxation and gastric emptying. In addition, it has been known that gastric emptying and gastric adaptive relaxation closely relate to functional dyspepsia.

Aims & Methods: In the present study we evaluated 20 amino acids on the gastric emptying and gastric accommodation to find useful amino acid for the therapy of functional dyspepsia. Male SD strain rats were used after one night fasting. Breath test: Gastric emptying was evaluated by breath test (Uchida et al., J Pharmcol Sci. 2005). After the oral administration of liquid test meal containing [1-¹³C]acetic acid, rats were placed in the chamber. The expired air was collected at 5-min intervals until 70 min after the test meal administration, with additional measurements at 90 and 120 min. The ¹³CO₂ levels in the expired air were measured by placing the breath-sampling bags into the sample joint of the UBiT-IR300 infrared analyzer. Gastric emptying was evaluated by the change of expired ¹³CO₂, Cmax, Tmax and AUC120min. Amino acids were administered orally 30 min before test meal administration. Barostat study: Gastric accommodation was evaluated by barostat. Balloon was introduced into the stomach through the mouth of anesthetized rats without the need for balloon surgery (Uchida and Shimizu, J Smooth Muscle Res. 2012). The balloon volume increased gradually just after an increment in the balloon pressure (1 to 8 mmHg), and reached a plateau within 1 min. This increased volume just after the increment of the balloon pressure was defined as adaptive relaxation. Amino acids were administered orally 30 min before barostat study.

Results: There were no amino acids enhancing the gastric emptying. Tryptophan significantly delayed the gastric emptying as compared with control and significant enhanced the gastric accommodation. Many amino acids inhibited gastric emptying and enhanced gastric adaptive relaxation. Significant positive correlation was observed between gastric emptying (Tmax) and gastric accommodation. Above findings show that amino acids delaying gastric emptying enhance the gastric accommodation. Only aspartic acid significantly enhanced the gastric adaptive relaxation, but did not influence the gastric emptying.

Conclusion: Functional dyspepsia is divided into postprandial distress syndromes and epigastric pain syndromes. Early satiety is one of the postprandial distress syndromes. This disease is supposed to be caused by the dysfunction of gastric adaptive relaxation. In this study, we found that aspartic acid significantly enhanced the gastric adaptive relaxation, but did not influence the gastric emptying. Therefore, aspartic acid may become useful material for the therapy of early satiety.

Disclosure of Interest: None declared

P1103 THE HERBAL PREPARATION, STW 5, PRESERVES GASTRIC FUNCTIONAL ACTIVITY IN A NOVEL SEQUENTIAL STRESS MODEL FOR FUNCTIONAL DYSPEPSIA

M. T. Khayyal¹, W. Wadie¹, M. Farouk¹, H. El-Abhar¹, T. Efferth², H. Abdel-Aziz³

¹Department of Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, Egypt, ²Institute of Pharmaceutical Biology, Johannes Gutenberg University, Mainz, ³Scientific Department, Steigerwald Arzneimittelwerk, GmbH, Darmstadt, Germany

Contact E-mail Address: mtkhayyal@gmail.com

Introduction: One of the main gastric disorders encountered in functional dyspepsia (FD) is a delay in gastric emptying and changes in gastric functional activity. The present study was designed to observe whether the established efficacy of the multi-component herbal preparation STW5 in FD^1-4 could owe its beneficial effects at least in part to preservation of gastric emptying and other parameters of gastric function. STW5 consists of standardized extracts of Iberis amara, Melissa officinalis, Matricaria recutita, Carum carvi, Mentha piperita, Angelica archangelica, Silybum marianum, Chelidonium majus, and Glycyrrhiza glabra. A novel stress model for FD has been devised to resemble the clinical situation where FD has been attributed to emotional stress in early life, followed by further exposure to stress in adulthood⁵.

Aims & Methods: Weanling rats were separated from the mother cage for 3 hours/ day until day 21 from birth. After reaching adulthood 4 weeks later, they were restrained for 90 min / day for 1 week. During these sessions animals were given STW 5 orally in daily doses of 2 and 5 ml/Kg. One day after the last session, the gastric emptying time of the animals was determined using a phenol red meal. In a separate group of rats, blood samples were taken for assaying the stress hormones corticosterone and corticosterone releasing factor. Fundus strips were removed after sacrifice to test their sensitivity ex-vivo towards carbachol, serotonin, adrenaline and potassium chloride. Furthermore, duodenal homogenates were examined for expression of CSE, RelA, Nrf-2 and the tight junction proteins ZO-1 and occludin using qPCR.

Results: Rats subjected to the sequential stress procedure showed marked delay in gastric emptying, an effect which was counteracted dose dependently by STW5. Sensitivity of the fundus ex-vivo to the tested agents was markedly depressed by stress, but tended to be normalized after treatment with STW5. The stress hormone levels were elevated by the model but tended to be normalized by the herbal preparation. The expression of Nrf-2 and ZO-1 was reduced but that of occludin was raised by the model but normalized after treatment.

Conclusion: The results contribute to our understanding of the beneficial properties of STW 5 in FD. Thus the disturbance in gastric function often observed in patients with FD could be effectively prevented by the herbal preparation, STW5.

Disclosure of Interest: M. Khayyal: None declared, W. Wadie: None declared, M. Farouk: None declared, H. El-Abhar: None declared, T. Efferth: None declared, H. Abdel-Aziz Conflict with: employed by Steigerwald Arzneimittelwerk GmbH

P1104 ALDIOXA IMPROVES BOTH OF DELAYED GASTRIC EMPTYING AND IMPAIRED GASTRIC ACCOMMODATION, WHICH ARE PATHOPHYSIOLOGIC MECHANISM OF FUNCTIONAL DYSPEPSIA

T. Asano¹, S. Aida¹, K.-I. Tanaka¹, T. Masaoka², H. Suzuki², T. Mizushima¹

¹Department of Drug Discovery and Development, Faculty of Pharmacy, Keio University, ²Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

Contact E-mail Address: asano-ti@pha.keio.ac.jp

Introduction: Functional dyspepsia (FD) is a highly prevalent gastric functional disease defined as persistent or recurrent gastric discomfort and epigastric pain without underlying organic causes, in which delayed gastric emptying and impaired gastric accommodation play important roles. Although FD markedly reduces the patient’s quality of life, its therapeutic protocol, including pharmacotherapy, has not been established.

Aims & Methods: In order to find candidate drugs for FD by drug repositioning strategy, we here screened compounds that could improve delayed gastric emptying from a library of medicines already in clinical use. Gastric emptying in mice was assessed by the phenol red method or the [¹³C]-labeled acetic acid breath test. The intracellular cAMP level was determined by ELISA. Membrane fractions prepared from Chinese hamster ovary (CHO)-K1 cells expressing human α-2 adrenergic receptor and [³H]-clonidine were used in filter-binding assay. Gastric accommodation in rats was examined using a barostat apparatus.

Results: Aldioxa (dihydroxyaluminium allantoinate) is a medicine used clinically to treat gastric ulcers and gastritis. Oral administration of aldioxa improved clonidine (α-2 adrenergic receptor agonist)-induced delayed gastric emptying. The dose of aldioxa required to suppress delayed gastric emptying was much lower than that required to suppress indomethacin-induced gastric lesions in mice. Other gastroprotective drugs (geranylgeranylacetone and sucralfate) had no effect on delayed gastric emptying. Aldioxa also suppressed the delayed gastric emptying induced by restraint stress, but did not affect the basal level of gastric emptying in intact mice. Administration of allantoin, but not aluminium hydroxide, restored the gastric emptying. Treatment of cells with clonidine decreases intracellular cAMP levels, which could be suppressed by the simultaneous treatment with aldioxa or allantoin. Both aldioxa and allantoin inhibited clonidine binding to the α-2 adrenergic receptor. We also found that aldioxa or aluminium hydroxide but not allantoin restored gastric accommodation in rats subjected to wrap restraint stress.

Conclusion: Results suggest that the oral administration of aldioxa restores gastric emptying activity via its antagonistic activity on the α-2 adrenergic receptor, with the allantoin moiety of this drug is involved in this restoration. The results also suggest that the aluminium hydroxide moiety of aldioxa is involved in the improvement of impaired gastric accommodation. We propose that aldioxa is a candidate drug for FD, because its safety in humans has already been confirmed clinically and its ameliorating effect on both of delayed gastric emptying and impaired gastric accommodation are confirmed here.

Disclosure of Interest: None declared

P1105 RIFAXIMIN FOR THE TREATMENT OF FUNCTIONAL DYSPEPSIA: A DOUBLE-BLINDED RANDOMIZED PLACEBO-CONTROLLED TRIAL

V. Tan¹, K. Liu¹, F. Lam¹, I. Hung¹, W. K. Leung¹

¹Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong

Contact E-mail Address: vpytan@hku.hk

Introduction: Evidence suggests that gut dysbiosis may be partly causal in the genesis of pain and bloating in irritable bowel syndrome and treatment with the non-absorbable antibiotic rifaximin reduces these symptoms. Functional dyspepsia (FD), is another functional gastrointestinal disorder, where pain, bloating and belching can be particularly problematic. We evaluated a two-week course of rifaximin for the treatment of FD.

Aims & Methods: Consecutive subjects with a diagnosis of FD according to the ROME III criteria with a normal gastroscopy were recruited from two centres in Hong Kong. Subjects were randomized into two treatment arms, 400mg three times a day (TDS) of rifaximin or 400mg TDS of placebo. The investigators and study subjects were blinded to the allocation. Subjects were followed for 8 weeks in total. The primary end point of adequate relief of global IBS symptoms and the key secondary end points of adequate relief of bloating or belching, were assessed at week-2, week-4 and week-8. Lactulose hydrogen breath test was performed at baseline and at the end of the study.

Results: A total of 86 subjects were randomized to either rifaximin or placebo. Significantly more subjects in the rifaxmin than in the placebo group experienced adequate relief of global FD symptoms at the end of the study period, week 8 (76.5% vs. 52.6%, P=0.04), with a strong trend in the preceding 6 weeks favouring rifaximin. Rifaximin was also superior to placebo in providing adequate relief of belching and bloating in subjects at week-4 however this improvement did not endure to week-8. Finally, a sub group analysis revealed that female subjects experienced earlier (79.2% vs. 40.6%, P=0.006 at week 4) and more sustained improvements in their global dyspeptic symptoms (80.0% vs. 51.6%, P=0.048 at week 8), as well as improvements in their belching and bloating at week-4. The oro-caecal transit time as measured by the lactulose hydrogen breath test was prolonged in subjects treated with rifaximin compared to baseline however there were no differences between subjects in terms of hydrogen production as measured by area under the curve calculations. The incidence of adverse effects were similar in both groups.

Conclusion: In subjects who met the ROME III criteria for FD, treatment with rifaximin led to adequate relief of global dyspeptic symptoms, belching and bloating. This was particularly marked in female FD subjects.

Disclosure of Interest: None declared

P1106 ACTIVATION OF DUODENAL BITTER TASTE RECEPTOR BY QUININE HYDROCHLORIDE EFFECTS ON INTRAGASTRIC PRESSURE PROFILES AND NUTRIENT TOLERANCE IN HEALTHY VOLUNTEERS

M. Ottenburgs¹, J. Tack¹, A. Rotondo¹

¹KULeuven, Leuven, Belgium

Contact E-mail Address: alessandra.rotondo@med.kuleuven.be

Introduction: Bitter taste receptors are expressed in the stomach and the duodenum but their function is unclear. We previously reported inhibition of gastric accommodation and nutrient volume tolerance by intragastric administration of bitter tastants¹.

Aims & Methods: We assessed the effects of duodenal infusion of a potent bitter tastant, quinine hydrochloride (QHCl) on intragastric pressure (IGP, a measure of gastric accommodation), nutrient tolerance and satiation.

We conducted a single-blind cross-over trial in healthy volunteers (HVs) with intraduodenal administration (via a feeding catheter) of 10 μmol/kg QHCl or placebo 30 min before the experimental protocol started.

A high-resolution manometry (HRM) probe was placed via the nose till the duodenum in 12 HVs (age 27 ± 3; BMI 22 ± 1). A nutrient drink (ND; 30% fat, 42% carbohydrate, 28% protein) was intragastrically infused (60mL/min) until maximum satiation, when it was stopped. Satiation score was scored every minute on a 0-5 scale. Thereafter, IGP was measured for 2 hours after the meal. During the entire experiment, HVs were asked to their sensations of hunger, appetite and the epigastric symptoms (fullness, bloating, nausea, belching, cramps and pain), every 5 min on a 10-cm horizontal visual analogue scale (VAS).

IGP was measured as average pressure over 5 channels in the fundus at least 1 cm below the LES; 5 minutes before ND start was taken as baseline. All data are expressed as mean ± SEM. Outcomes of ND tolerance, total area above the curve (AAC) and max IGP drop during ND infusion, AAC of satiation score and VAS during both conditions were compared with a paired t-test.

Results: The intraduodenal administration of placebo or QHCL did not affect baseline IGP profile or symptoms. During the intragastric ND infusion, the IGP decreased initially and gradually increased thereafter in both conditions. QHCl administration failed to affect the max IGP drop (6.4 ± 0.6 mmHg for placebo vs 5.7 ± 0.7 mmHg for QHCl, ns), or the AAC (61 ± 11 mmHg*min for placebo vs 57 ± 12 mmHg*min for QHCl, ns) indicating a lack of an effect on gastric accommodation. Also the post-prandial IGP profile did not differ between both treatment arms. However, satiation scores after QHCl tended to be lower than in placebo (AUC 118 ± 6 ml vs. 107 ± 6 ml; p = 0.09) and the volume of ND ingested at maximum satiation was significantly higher after QHCl (835 ± 138 ml vs. 1031 ± 116 ml, p = 0.05).

Conclusion: In contrast to intragastric administration effects, intraduodenal administration of the bitter agonist QHCL did not affect gastric accommodation, but tended to inhibit meal-induced satiation and increased nutrient volume tolerance. The mechanism involved in this orexigenic action of intra-duodenal QHCL warrants further study.

Disclosure of Interest: None declared

P1107 DOES AN IMPAIRMENT OF ANTIOXIDANT CAPACITY IN OBESE HUMAN GASTRIC ANTRUM CAUSE THE ALTERATION IN VASOACTIVE INTESTINAL PEPTIDE (VIP)- PATHWAY?

A. Scirocco¹, M. Carabotti¹, G. Silecchia¹, A. Ignazzi², G. Tellan¹, L. Pallotta¹, A. Cicenia¹, M. A. Maselli², E. Corazziari¹, C. Severi¹

¹University Sapienza, Rome, ²Irccs “Saverio de Bellis”, Castellana Grotte (BA), Italy

Contact E-mail Address: annunziata.scirocco@uniroma1.it

Introduction: Genome-wide association analysis has identified a relation between obesity and the Vasoactive Intestinal Peptide (VIP) pathway. Obesity is characterized by systemic oxidative stress with an imbalance between the increase in reactive oxygen species (ROS) production and the decrease in cellular antioxidant capacity. Low levels of antioxidant capacity may impair cell signaling pathways in terms of membrane G proteins, second messengers (ie.cAMP) and transcripts encoding for endothelial nitric oxide synthase (eNOS). These signaling pathways and messengers are involved in vasoactive intestinal peptide (VIP), induced relaxation of human gastric antrum.

Aims & Methods: Aim of this study was to evaluate in obese patients oxidant capacity and its influence on antrum smooth muscle relaxation. Smooth muscle cells (SMC) and strips were isolated from human gastric antrum obtained from 14 normoglycemic-normocholesterolemic morbid obese patients (40.92; 372; 56 Antioxidant capacity was evaluated by antioxidant assay kit and the contribution of oxidative stress by the use of Apocynin (APO:1µg/ml) that inhibits NADPH oxidase the main producer of ROS. VIP (1μM) relaxant effects were tested on maximal cholecystokinin (CCK 1nM)-induced contraction on SMC and strips whilst the effect of adenylate cyclase activator forskolin (FSK,10 mM) and the 2nd messenger cAMP (0.1 mM) only on SMC. qPCR analysis was performed for transcripts for VPAC2, inflammatory cytokine (COX-2) and eNOS, the data were normalized to β-actin mRNA levels. Data are expressed as mean ± SE, p < 0.05 considered significant.

Results: Obese gastric muscle presented a low antioxidant capacity (30 ± 12 equivalent of trolox) associated to an hyporesponsiveness to VIP. In obese, VIP-induced relaxation was reduced both in SMC (14.5 ± 7.3%, p < 0.05) and strips (13.8 ± 5.2%, p < 0.05) in comparison to control (SMC:79.96 ± 5.78% ; strips: 78.1 ± 7.4%). This reduced VIP effect was associated in SMC with: 1) a decrease of VPAC2 messenger (obese: 3.63 ± 0.06 vs control: 6.27 ± 0.79, p < 0.05); 2) no transcripts for eNOS that was present in control (6.6± 0.4); 3) an increase of COX2 messenger (obese: 4.93 ±0.63 vs control: 1.10 ± 0.08, p < 0.05); 4) an impairment of cAMP- and FSK- induced SMC relaxation, in comparison to control (cAMP: 44.9 ± 7.6 vs 73.4 ± 5.8%; FSK: 54.95 ± 2.3 vs 71.80 ± 11.8%, p < 0.05). The inhibition of NADPH oxidase by APO partially restores all these alterarations. A 2-fold increase of antioxidant capacity was observed (50 ± 0.5 equivalent of trolox), such as VIP-induced relaxation was restored (79.60 ± 11.84). VPAC2 messenger expression increase (4.02 ± 0.03, p < 0.05) as well as eNOS messenger (1.12 ± 0.08, p < 0.05).

Conclusion: An impairment of antioxidant capacity in human obese is are involved in alteration of VIP- induced relaxation of gastric antrum.

Disclosure of Interest: None declared

P1108 IMPACT OF TACRINE AND 7-METHOXYTACRINE ON GASTRIC MYOELECTRICAL ACTIVITY ASSESSED USING ELECTROGASTROGRAPHY IN EXPERIMENTAL PIGS

J. Bures¹, D. Jun²³, M. Hrabinova³, I. Tacheci¹, J. Kvetina¹, M. Pavlik³, S. Rejchrt¹, T. Douda¹, M. Kunes², K. Kuca², M. Kopacova¹

¹2nd Department of Internal Medicine - Gastroenterology, Charles University Faculty of Medicine and University Teaching Hospital, ²Biomedical Research Centre, University Hospital , ³Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic

Contact E-mail Address: bures@lfhk.cuni.cz

Introduction: Tacrine was the first acetylcholinesterase inhibitor approved for therapy of Alzheimer’s disease. Tacrine has dose-limiting side effects, including diarrhoea, nausea, vomiting and abdominal discomfort. It has currently been withdrawn in some countries mostly due to the risk of hepatotoxicity and been replaced by its derivate 7-methoxytacrine (7-MEOTA).

Aims & Methods: The aim of this study was to assess the impact of these two compounds on gastric myoelectrical activity by means of surface cutaneous electrogastrography (EGG) in experimental pigs.

Twelve pigs (Sus scrofa f. domestica, weighing 30-35 kg) entered the study. A single dose of tacrine (200 mg i.m., n=6) or 7-MEOTA (200 mg i.m., n=6) was administrated. Cholinesterase (acetylcholinesterase and butyrylcholinesterase) activity was determined in whole blood. Acetylcholine iodide was added as a substrate and liberated acetic acid was titrated with sodium hydroxide using an automatic titrator in potentiostatic mode. All EGG recordings were performed under general anaesthesia in the morning after 24 hours of fasting. Basal (30 minutes) and study recordings (150 minutes) were accomplished using an EGG stand (MMS, Enschede, the Netherlands). Running spectral analysis based on Fourier transform was used. Results were expressed as dominant frequency of gastric slow waves, power analysis (areas of amplitudes) and power ratio assessment (ratio of the areas of amplitudes after and before study drug administration).

Results: Maximal inhibition of blood cholinesterase activity was recorded after 10 minutes, being significantly stronger after administration of tacrine (20.5 ± 19.2%) compared to 7-MEOTA (72.8 ± 14.4%), p < 0.001. Tacrine decreased EGG dominant frequency 10 minutes after its administration (from basal 3.1 ± 0.6 to 2.8 ± 0.6 cycles per minute; p = 0.014). Tacrine induced a 60-minute but not significant increase of the power (with maximal value 493 ± 533 μV² at 20 minutes; p = 0.300) and power ratio (with maximal value 2.04 ± 3.4 at 10 minutes; p = 0.330). Tacrine caused significant gastric arrhythmia. 7-MEOTA did not influence dominant frequency of gastric slow waves significantly. 7-MEOTA caused a short-term late increase of the power (from basal 618.3 ± 747.3 to 2540.2 ± 6130.3 μV² at 90 minutes; p = 0.079) and power ratio at 60 minutes (6.3 ± 11.2; p = 0.003). Blood cholinesterase activity did not correlate with any EGG parameter either after tacrine or 7-MEOTA at any time.

Conclusion: Tacrine and 7-MEOTA have different impacts on EGG. Tacrine decreased dominant frequency and induced long-lasting gastric arrhythmia. 7-MEOTA caused a short-term late increase of the EGG power in experimental pigs.

Acknowledgements: the study was supported by an independent research grant (NT/14270).

Disclosure of Interest: None declared

P1109 THE EFFECT OF NEOSTIGMINE ON PORCINE GASTRIC MYOELECTRIC ACTIVITY ASSESSED USING ELECTROGASTROGRAPHY

M. Kopacova¹, J. Kvetina², I. Tacheci¹, M. Pavlik³, S. Rejchrt¹, T. Douda¹, M. Kunes⁴, J. Bures¹

¹IInd. Dpt. of Internal Medicine - Gastroenterology, Charles University in Praha, Faculty of Medicine at Hradec Kralove, University Teaching Hospital, ²Institute of Experimental Biopharmaceutics, Czech Academy of Sciences, ³Centre of Advanced Studies, University of Defence, Faculty of Military Health Services, ⁴Biomedical Research Centre, Charles University in Praha, Faculty of Medicine at Hradec Kralove, University Teaching Hospital, Hradec Kralove, Czech Republic

Contact E-mail Address: marcela.kopacova@fnhk.cz; bures@lfhk.cuni.cz

Introduction: Neostigmine is a parasympathomimetic agent that acts as a reversible acetylcholinesterase inhibitor. By interfering with the breakdown of acetylcholine, neostigmine indirectly stimulates both nicotinic and muscarinic receptors. However, there are no data on the direct effect of neostigmine on gastric myoelectrical activity.

Aims & Methods: The aim of this study was to assess the impact of neostigmine on the myoelectrical activity of the stomach by means of non-invasive surface cutaneous electrogastrography (EGG) in experimental pigs. Porcine EGG is fully comparable with human EGG so it is suitable for various preclinical studies. Six adult female pigs (Sus scrofa f. domestica; 3 - 4 months old; mean weight 31.2 ± 2.1) entered the study. EGG recordings were performed under general anaesthesia (2% isoflurane in medicinal oxygen) in the morning after 24 hours of fasting. After the EGG baseline, neostigmine was administrated to the animals (0.5 mg i.m.; Neostigmini metilsulfas). EGG was followed by a 90-minute trial recording (MMS, Enschede, the Netherlands). Running spectral analysis based on Fourier transform was used for the evaluation. The results were expressed as dominant frequency of gastric slow waves and EGG power (areas of amplitudes).

Results: Neostigmine continuously increased the dominant frequency from basal EGG 2.6 ± 0.5 cycles per min. up to 2.9 ± 0.6 at the 60-90-minute interval (p < 0.001). Neostigmine continually decreased the EGG power from baseline values 1767.4 ± 2179.5 µV² (median 861.5) to 594.3 ± 853.8 µV² (median 151.0) at the 5-10-minute interval (p = 0.036), throughout until the 60 - 90-minute interval 117.6 ± 157.5 µV² (median 60.5; p < 0.001).

Conclusion: The standard dose of neostigmine significantly increased the dominant frequency of gastric slow waves and caused a continual long-lasting decrease of EGG power in experimental pigs.

Acknowledgements: the study was supported by an independent research grant (NT/14270).

Disclosure of Interest: None declared

P1110 ASSOCIATION BETWEEN THE TYPE OF ACHALASIA ESTABLISHED USING HIGH-RESOLUTION MANOMETRY (HRM) AND CHANGES OF PLASMA TOTAL CONCENTRATION OF NITRIC OXIDE METABOLISM END PRODUCTS

O. Storonova¹, A. Trukhmanov¹, Y. Evsyutina¹, V. Ivashkin¹

¹I.M. Sechenov First State Moscow Medical University, Moscow, Russian Federation

Contact E-mail Address: storonova@yandex.ru

Introduction: Previous studies have shown a decrease of nitric oxide (NO) metabolites level in patients with achalasia. However, the relationship between the type of achalasia and the level of plasma total concentration of NO metabolism (nitrates and nitrites) end products remains unknown.

Aims & Methods: to determine association between the type of achalasia and changes of plasma total concentration of end products of NO metabolism. 18 patients with achalasia (median age was 51.5 years (30-72) and 15 healthy volunteers were studied. We performed on every patient a high-resolution manometry (HRM) using a 22 channels silicone water-perfused catheter (Solar GI, MMS, Netherlands), and determined the total concentration of nitrates and nitrites. We analyzed HRM parameters: lower esophageal sphincter (LES) resting pressure (RP), integrated relaxation pressure (IRP), esophageal pressurization and distal contractile integral (DCI) according to the Chicago classification (version 3.0). The statistical analyses were performed using Statistica for Windows 6.0 (StatSoft Inc.).

Results: Type I achalasia was established in 10 patients (55.5%), type II in 5 patients (27.8%), and type III in 3 patients (16.7%). We detected an increase of IRP in all patients (21.0 mmHg (18.0; 35.2); p<0.001), an increase of LES RP in 6 patients (33.3%) - 27.0 mmHg (19.0; 67.4), a decrease of DCI (290 mmHg (0-750)) in 14 (77.8%). Pan-esophageal pressurization revealed in 5 patients (27.8%), hypercontractile contractions in the distal part of the esophagus (DCI 5340 mmHg (3500; 6750)) - in 3 (16.7%). In patients with achalasia in comparison to healthy volunteers, we showed a decrease of NO metabolites (24.2 umol/l (20.5; 30.5) vs 36.8 umol/l (30.8; 48.6); p<0.05). In patients with type II and III achalasia the level of NO metabolites was lower than in control group (25 umol/l (15.0; 33.5) and 22 umol/l (6.9; 30.5), respectively). Patients with type I had a normal trend (33.2 umol/l (29.9; 36.7)).

Conclusion: The level of NO metabolites depends on type of achalasia. Patients with type I achalasia have normal level of NO metabolites, while it is lower in patients with type II and to a greater extent with type III achalasia.

Disclosure of Interest: None declared

P1111 A NOVEL ROLE FOR THE EXTRACELLULAR MATRIX GLYCOPROTEIN-TENASCIN X IN GUT FUNCTION

R. Aktar¹, M. Peiris¹, S. Eaton², S. Kritas³, S. Kentish⁴, E. Araujo De Almeida⁵, A. Page⁴, Q. Aziz¹, A. Blackshaw¹

¹Digestive Diseases, Queen Mary University Of London, ²Institute of Child Health, University College London, London, United Kingdom, ³Translational Research in GastroIntestinal Disorders, KU Leuven, Leuven, Belgium, ⁴Medicine, The University of Adelaide, Adelaide, Australia, ⁵Enteric neurobiology, Londrina State University, Londrina, Brazil

Contact E-mail Address: r.aktar@qmul.ac.uk

Introduction: Joint hypermobility syndrome (JHS) is a non-inflammatory connective tissue disorder commonly associated with gastrointestinal (GI) symptoms [1]. Ehlers-Danlos syndrome type III is a form of JHS where patients lack the Tenascin X (TNX) gene, an extracellular matrix glycoprotein. Clinically these patients manifest GI symptoms including constipation and rectal prolapse [2]. TNX knockout mice (KO) similarly suffer from rectal prolapse [3]. Previously we have shown TNX associates with vagal afferent calretinin+ nerve endings in wild type (WT) mouse stomach. In colon, TNX strongly associates with cholinergic, ChAT+ myenteric and submucous plexus neurones [4]. Therefore, localisation of TNX around nerve endings in stomach may affect gastric motor function, while association with cholinergic excitatory motor neurons suggests a role in contraction. We hypothesise TNX is important for regulating normal gastric and colonic function.

Aims & Methods: To establish the functional role of TNX in the stomach and colon using TNX KO mice. Methods: Gastric emptying rate was determined using ¹³C octanoic acid breath test (WT:n=13, KO:n=9). From ¹³CO₂ curve, T½ (time for 50% of stomach emptying to occur) and T Lag (initial time delay in gastric emptying) were calculated. Colonic motility was assessed by manometry using a multi-lumen catheter, in an ex vivo colonic preparation (WT:n=6, KO:n=6). The number and amplitude of spontaneous contractions occurring throughout the colon over a 30 min study period were determined. Student’s t-test was used to calculate statistical significance based on ± SEM for gastric emptying, and 2-way ANOVA for colonic motility.

Results: Gastric emptying was significantly accelerated in KO mice compared to WT (T½: WT=158 ± 21.8 min vs. KO=103 ± 12.9 min; p=0.0277). Similarly, T Lag was significantly shorter in KO mice (T Lag: WT=38 ± 5.7 min vs. KO=24 ± 2.7 min; p=0.0194). In the two groups colonic motility was measured in the following regions: Proximal, Mid-Proximal, Mid-Distal and Distal colon. Number of spontaneous contractions significantly decreased in all regions of the colon except for the proximal segment in KO mice compared to WT (Proximal: WT=4.2 vs. KO=5.6; Mid-Proximal: WT= 11.6 vs. KO= 3.17; Mid-Distal: WT=11.6 vs. KO=3.80; Distal: WT=11.0 vs. KO=3.20; p<0.05). However, the mean amplitude of contractions significantly decreased only in the distal region of the colon in TNX KO mice (WT=32mmHg vs. KO= 12mmHg; p=<0.05).

Conclusion: In summary, we have identified two roles for the extracellular matrix glycoprotein-TNX. A loss of TNX causes accelerated gastric emptying which suggests that TNX is important in regulating gastric vagal afferent nerve activity. Also the absence of TNX causes a decrease in colonic contraction indicating TNX is needed to form the extracellular matrix around neurones important for neural communication, particularly in the cholinergic excitatory pathway. Collectively, the anatomical and functional data provide evidence that TNX is important in mediating normal gastric and colonic motor function.

Disclosure of Interest: None declared

P1112 THE EXPRESSION OF NEUROTROPHINS AND NEUROTROPHIC FACTORS IN THE ACUTE MODEL OF EOSINOPHILIC INFLAMMATION OF THE ESOPHAGUS

A. Stefanikova¹, J. Hatok¹, P. Racay¹, L. Mazurova², M. Tatar², M. Kollarik²³, M. Brozmanova²

¹Department of Medical Biochemistry, ²Department of Pathophysiology, Comenius University in Bratislava, Jessenius faculty of Medicine in Martin, Martin, Slovakia, ³Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, United States

Contact E-mail Address: aastefanikova@gmail.com

Introduction: Eosinophilic esophagitis is characterized by symptoms related to esophageal dysfunction (dysphagia, heartburn, and food impaction). Esophageal nerves regulate esophageal sensory and motor function, and alterations in these nerves are predicted to worsen esophageal dysfunction. However, it is unknown whether the eosinophilic inflammation in the esophagus leads to production of neurotrophins and neurotrophic factors that can induce profound alterations in peripheral nerves.

Aims & Methods: Here we aimed to characterize eosinophilic infiltration in the guinea pig model of acute allergic inflammation of the esophagus, and to evaluate changes in the expression of selected neurotrophins and neurotrophic factors in esophageal mucosa in this model. The antigen ovalbumin (OVA, 0.1% in saline) was injected into the surgically exposed cervical esophagus in the OVA-sensitized guinea pigs. The esophagus (middle portion) was harvested at various time points (2-14 days) and the eosinophil counts were evaluated in transversal sections (12µm) by using Giemsa staining. The expression of neurotrophins (NGF, BDNF) and neurotrophic factors (GDNF, artemin) was evaluated by quantitative RT-PCR. NGF, BDNF, GDNF and artemin were selected because esophageal nerves have receptors for these neurotrophins and neurotrophic factors.

Results: Eosinophils were rare in the esophagus of control naïve animals that received a vehicle injection or no injection. The maximal number of eosinophils per high power filed (hpf) was 5 ± 2 (n=6). OVA injection into the esophagus in sensitized animals resulted in massive eosinophil infiltration of esophageal mucosa (97 ± 24 eosinophils per hpf, n=10, p < 0.05 vs. control) on day 2 following the injection. The number of eosinophils was reduced on day 5 (27 ± 16, n=4) and further reduced on day 14 (10 ± 6, n=3), therefore the day 2 was selected for qRT-PCR analysis. The expression of BDNF was increased in the inflamed compared to control esophagus. dCT (detection threshold expressed relative to detection threshold of housekeeping gene b-actin) was 10.8 ± 0.5 vs. 9.8 ± 0.2 in control (n=6) and inflamed (n=7) esophagus, respectively, indicating twofold (ddCT=1, 2^ddCT=2) increase in BDNF mRNA (p < 0.05). In contrast the expression of artemin was moderately (to approximately 60%) reduced (dCT was 9.0 ± 0.2 vs. 9.7 ± 0.1, ddCT=-0.7, 2^ddCT=0.6, p < 0.01). The expression of NGF (8.8 ± 0.4 vs. 8.7 ± 0.2, p = 0.8) and GDNF (12.5 ± 0.3 vs. 12.3 ± 0.2, p = 0.5) was not changed.

Conclusion: An acute allergen challenge in the esophagus leads to robust eosinophilic infiltration of esophageal mucosa that is associated with changes in the expression of neurotrophins and neurotrophic factors. This model is suitable for the analysis of esophageal nerve plasticity in eosinophilic inflammation. Supported by BioMed Martin (ITMS: 26220220187) and VEGA 1/0070/15.

Disclosure of Interest: None declared

P1113 OBJECTIVE BIOLOGICAL MARKERS OF MEAL-INDUCED PERCEPTION

C. Malagelada¹, I. Barba², S. Mendez¹, C. Alonso¹, A. Accarino¹, F. Azpiroz¹

¹Digestive Diseases Unit, Hospital Vall d'Hebron, ²Experimental Cardiology Laboratory, Vall d'Hebron, Institut de Recerca, Barcelona, Spain

Contact E-mail Address: cmalagelada@gmail.com

Introduction: We have previously shown that meal ingestion induces cognitive perception (sensations) with a hedonic dimension (well-being) that depend on the characteristics of the meal and the appropriateness of the digestive response.

Aims & Methods: The aim of the present study is to identify biomarkers of the cognitive response to meal ingestion.

In 18 healthy subjects, selected through a clinical questionnaire to determine the absence of gastrointestinal symptoms, the response to a test meal (Edanec, 1 kcal / ml) at an intake rate of 50 ml / min until maximum satiety were assessed. Perception measurements and blood samples for metabolomics analysis was taken at 5 min intervals before, during and 20 minutes after ingestion. Perception of hunger/satiety, desire of eating a food of choice, digestive well-being, abdominal fullness and discomfort/pain was measured on 10 cm scales. Metabolomic analysis was performed with MRI spectroscopy. Discriminative metabolites (determined by principal component analysis) were determined and quantified as the area under the peaks of the MRI spectra. Values of glucose, triglycerides, insulin, PYY and GLP-1 were measured using conventional laboratory techniques.

Results: During ingestion satiety progressively increased up to a maximum sensation (+5 score on a scale from -5 to +5) after ingestion of 976 ± 71 ml. Ingestion induced sensation of fullness and decreased digestive well-being. Twenty minutes after the meal, these sensations had partially recovered down to fasting levels. The total amount ingested by each subject correlated with basal sensation of hunger (R = 0.8; p = 0.0001), but not with other sensations or blood metabolites levels measured during fasting. Immediately after ingestion, satiation correlated with an increase in glucose (R = 0.49; p = 0.038) and valine levels (R = 0.48; p = 0.043), while well-being inversely correlated with CH3-lipids (R = -0.72; p = 0.001). Fullness sensation was associated with lower levels of GLP (R = -0.77; p = 0.001) and PYY (R = -0.63; p = 0.015). Twenty-minutes after finalizing ingestion, triglyceride levels had significantly increased and correlated with the decrease in desire to eat a food of choice (R = -0.56; p = 0.016). Throughout study, the increase in CH2-lipids correlated with lower discomfort (R = -0.51; p = 0.032).

Conclusion: Cognitive (sensations) and hedonic responses (well-being) to meal ingestion correlate with changes in circulating metabolites, that may serve as objective biomarkers of perception.

Disclosure of Interest: None declared

P1114 SHORT-TERM NON-INVASIVE AFFERENT VAGUS NERVE STIMULATION (NVNS) USING GAMMACORETM (GC) IN PATIENTS WITH TREATMENT REFRACTORY GASTROPARESIS

E. Paulon¹, D. Nastou², F. Jaboli², O. Epstein²

¹Gastroenterology, ²Institute for Minimally Invasive Gastroenterology, London, United Kingdom

Contact E-mail Address: emma.paulon@gmail.com

Introduction: High-frequency, low-energy gastric neurostimulation(Enterra™) is indicated for compassionate treatment of patients with refractory gastroparesis. Symptom improvement is reported in 50-60% of patients but not accompanied by improved gastric emptying. It is likely that gastric neurostimulation affects the gut-brain axis influencing autonomic afferents (1). GammaCore(electroCore, LLC) is a non-invasive, afferent selective vagus nerve stimulator(nVNS) used for the treatment of migraine and cluster headache. We report the first use of gC in patients with refractory gastroparesis.

Aims & Methods: Thirty-five consecutive patients with intractable gastroparesis were invited to undergo a course of gC whilst awaiting funding for implantable gastric neurostimulation. The gC device delivers a high-frequency, low-energy stimulus to afferent vagus fibers as they cross the neck adjacent to the carotid arteries. The device is programmed to deliver doses of 120 seconds and patients were trained to deliver 2 doses (240 secs) to the left and right vagus nerve respectively. This dosing regimen was self-administered 8 hourly (12 doses/day) for 2 weeks, increasing in week 3 to 3 doses 8 hourly (18 doses/day). Patients were asked to grade their symptoms daily using the 9 item Gastroparesis Cardinal Symptom Index (GCSI)with a 5 point Likert scale. The GCSI was completed for 2 weeks prior to commencing treatment, and throughout the treatment period. Symptom change was evaluated in patients who complied with treatment and completed the daily symptom score. The mean aggregated GSCI score at baseline was compared with the aggregated score of the final week of treatment. Clinically meaningful improvement was defined as a GCSI Likert scale reduction of ≥1 (2).

Results: Twenty-three of the 35 patients (65.7%) used the gamma Core as instructed and completed the daily diary. The pre-treatment mean aggregated GCSI score in these patients was 2.85 (SD 0.90). At 3 weeks,8 patients (35%) had a ≥1 reduction in the aggregated GSCI score. Two compliant patients who continued stimulation for more than three weeks experienced a delayed response, giving a total response rate of 43%. In 8 of the responders, improvement was evident within 1 week of commencing treatment whilst a response was evident in the 2 patients who continued treatment for >3 weeks by week 5. All the responders experienced symptom recurrence within a week of stopping treatment. No serious adverse events device related were reported.

Conclusion: In this group of patients with treatment refractory gastroparesis, one third failed to engage with short term nVNS. In compliant patients, 43% recorded a fall of ≥1 in their aggregated GCSI score. As gC stimulates afferent vagus fibers, it is likely that the response is mediated at the level of the gut-brain axis. In refractory gastroparesis, nVNS delivered by gC might offer a new approach to symptom control. The dosing and duration of nVNS required to obtain an optimal response remains unknown and deserves further consideration.

Disclosure of Interest: None declared

P1115 PHYSIOLOGICAL AND ELECTRICAL MODULATION OF VAGAL TONE ENHANCES ANTRODUODENAL MOTILITY IN HEALTHY HUMANS

S. Bergmann¹, C. Brock¹, A. D. Farmer¹², J. B. Frokjaer¹, A. Madzak¹, J. Ellrich³, A. M. Drewes¹

¹Mech-Sense, Aalborg University Hospital, Aalborg, Denmark, ²Wingate Institute of Neurogastroenterology, Barts and the London, London, United Kingdom, ³Department of Health Science and Technology, Aalborg University , Aalborg, Denmark

Contact E-mail Address: a.farmer@qmul.ac.uk

Introduction: The autonomic nervous system is a bidirectional hierarchically controlled brain body nexus that integrates the external environment with the internal milieu. The parasympathetic nervous system (PNS), whose main neural substrate is the vagus nerve, influences antro-duodenal motility. In animal models, the stimulation of vagal afferents have been shown to enhance antro-duodenal motility. Hitherto, the influence of physiological and electrical modulation of vagal tone in humans on antroduodenal motility has not been objectively evaluated.

Aims & Methods: To investigate the synergistic effects of physiological (deep slow breathing (DSB)), and electrical (transcutaneous auricular vagal nerve stimulation (t-VNS)) modulation of vagal tone on antro-duodenal motility. 12 healthy subjects (9 female, median age 52.5 years, range 40-56) were randomized to receive either DSB/active t-VNS or sham-DSB/sham t-VNS in a crossover design. Cardiac vagal tone, a validated real time non-invasive parameter of efferent PNS tone from the brainstem (1), was measured at baseline and continuously thereafter. Antro-duodenal motility was assessed after 90 minutes of stimulation/sham using a validated real-time ultrasonographic method in response to a standardized liquid meal (2).

Results: In comparison to the sham condition, DSB/active t-VNS resulted in an increase in vagal tone (8.7 linear vagal scale +/- 3.8 vs. 6 +/- 3.9, p=0.02). DSB/active t-VNS increased the frequency of antro-duodenal contractions (9.1 contractions/3 minutes +/- 2 vs. 7.1 +/- 1.9, p=0.04) compared to sham. DSB/active t-VNS increased antroduodenal motility index (5.6 +/- 2.5 vs. 3.7 +/- 2.1, p=0.048) compared to sham.

Conclusion: These findings provide preliminary evidence to suggest that DSB/active t-VNS increases cardiac vagal tone. Moreover, antroduodenal motility can be enhanced via physiological and electrical modulation of vagal tone. Such interventions warrant further exploration in patients groups such as those with functional dyspepsia.

Disclosure of Interest: None declared

P1116 ROLE OF DELAYED GASTRIC EMPTYING AS PREDICTOR OF CARDIOVASCULAR EVENT IN PATIENTS WITH SYMPTOM OF GASTROPARESIS

S.-Y. Park¹, J.-S. Rew¹, H.-S. Kim¹, C.-H. Park¹, S.-K. Choi¹, D.-H. Lee¹

¹Chonam National University Hospital, Gwangju, Korea, Republic Of

Contact E-mail Address: drpsy@naver.com

Introduction: Gastroparesis is a chronic disorder that significantly impairs the quality of life of affected individuals. However, little is known about the prognosis for morbidity or death of delayed gastric emptying. The aim of study was to evaluate the prognostic value of gastric emptying study on the prediction of morbidity including cardiovascular event.

Aims & Methods: We enrolled 139 patients (93 females, 105 patients with diabetes) with symptoms of gastroparesis, who underwent gastric emptying scintigraphy from 2004 to 2013. Comorbid condition, age, gender distribution were examined as potential risk factors. We evaluated the occurrence of cardiovascular events (coronary artery disease, stroke) and other morbid diseases after gastric emptying scintigraphy.

Results: There were 114 patients with normal gastric emptying (NGE) and 25 with delayed gastric emptying (DGE). The mean age, gender, BMI and distribution of comorbid conditions including diabetes were not significantly different between the two groups. There was more frequent occurrence of cardiovascular event in ‘DGE’ than ‘NGE’ (32.0 % vs. 10.5 %, p =  0.011). There was more frequent occurrence of cardiovascular event and other neurologic disease in ‘DGE’ (40.0% vs. 14.9%, p = 0.009).

Conclusion: A delayed gastric emptying study may predict the occurrence of cardiovascular event and negative outcomes in patients with symptoms of gastroparesis.

Disclosure of Interest: None declared

P1117 GASTROPARESIS IN CHILDREN: CHARACTERIZATION AND CLINICAL PRESENTATION – A RETROSPECTIVE STUDY

K. Bruil¹², T. Catto-Smith¹², M. Oliver¹²

¹Gastroenterology and Clinical Nutrition, Royal Children's Hospital Melbourne, ²Theme Population Health - Gastro & Food Allergy, Murdoch Childrens Research Institute, Parkville, Australia

Contact E-mail Address: tony.cattosmith@rch.org.au

Introduction: Gastroparesis is commonly diagnosed on the basis of scintigraphy and is associated with symptoms of nausea, vomiting, early satiety and upper abdominal pain. The pathophysiology of this condition in adults and children is not clear and the literature describing the characteristics, aetiology, treatment and outcome of gastroparesis in the paediatric population is limited.

Aims & Methods: Aims of this study were to describe the clinical presentation and aetiology, comorbidities, diagnostic findings, treatments and outcomes in children with scintigraphic proven delayed gastric emptying.

A retrospective descriptive study at the Royal Children's Hospital in Melbourne was performed on patients (0-18 years) with scintigraphy proven delayed gastric emptying (DGE). We collected data from 2004-2008 on the clinical presentation, comorbidities, aetiologic factors, other diagnostic interventions, treatments and outcomes in these children. Sub-group analysis was performed to investigate (a) age and gender related differences in symptoms and comorbidities and (b) differences in outcome based on severity of delayed gastric emptying.

Results: One hundred and five patients were included in our study with 49% being boys and 51% being girls. Median age at presentation was 6.7 years (IQR 1.2 – 12.1). Boys tended to have a lower age at presentation compared to girls. The most common presenting symptoms were vomiting (61%), weight loss or failure to thrive (38%) and regurgitation (23%). Respiratory symptoms were more reported in males and infants. Nausea was more frequently seen in older children and females. Common comorbidities were gastro-oesophageal reflux (50%), respiratory (25%) and neurodevelopmental (21%). An idiopathic aetiology was seen in 74% of children and other causes were medication use, post viral and surgery. Additional investigations performed were a barium meal (71% of children) and endoscopy (66%). Treatment included diet (32%) and medications including a proton pump inhibitor (66%), a prokinetic (73%) and in 51% a combination of both. Over half the cohort had complete or partial resolution of symptoms. No differences in outcome were found with respect to severity of delayed gastric emptying.

Conclusion: Idiopathic gastroparesis was most common in our study group however, a substantial number of patients had a comorbidity. A variety of treatments were used and over half our cohort showed symptomatic improvement. It is important to note that there was no relationship between the severity of an objective test of gastroparesis and resolution of clinical symptoms. Future research is needed to develop a consensus on gastric emptying scintigraphy in children, to define subgroups and their disease mechanisms and to provide parents and doctors with more evidence based management approaches.

Disclosure of Interest: None declared

P1118 ESOPHAGEAL MOTILITY BEFORE AND AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION FOR SUPERFICIAL ESOPHAGEAL CANCER: A HIGH-RESOLUTION MANOMETRY STUDY

K. Takahashi¹, M. Takeuchi¹, Y. Sato¹, H. Sato¹, K. Mizuno², S. Hashimoto², M. Kobayashi², S. Terai¹

¹Division of Gastroenterology and Hepatology, ²Department of endoscopy, Niigata University Medical and Dental Hospital, Niigatashi, Japan

Contact E-mail Address: kazuya911@hotmail.co.jp

Introduction: Endoscopic submucosal dissection (ESD) is a standard treatment for superficial esophageal cancer (EC). Postoperative stricture is one of the most common complications in esophageal ESD, and patients with postoperative strictures often suffer from dysphagia. Recently, procedures to prevent strictures, such as endoscopic balloon dilatation (EBD), endoscopic triamcinolone injection (ETI) and oral administration of prednisolone, have made it possible to avoid postoperative strictures more effectively. Nonetheless, some patients complain of dysphagia after ESD, although no postoperative strictures may be present. Although ineffective esophageal motility may be associated with dysphagia after ESD, levels of esophageal motility after ESD remain unknown.

Aims & Methods: The aim of this study was to elucidate the esophageal motility before and after ESD and the cause of dysphagia using high-resolution manometry (HRM).

Fifteen male patients (mean age: 69.8 years) who underwent ESD for superficial EC were enrolled in this study. Patients filled out a questionnaire about dysphagia and underwent HRM before and after ESD. The results of the HRM tests were analyzed according to the metrics and contraction patterns in the Chicago classification, version 3. All results were compared between before and after ESD.

Results: Data were obtained from 14 patients. The average size of the circumferential mucosal defect ratio at ESD was 52.1 ± 19.3% and 2 patients had more than sub-circumferential resection. The distal contractile integrity (DCI) before and after ESD and the frequencies of ineffective or fragmented contractions were not significantly different (1942.4 ± 1692.9 vs. 1907.8 ± 1515.9 mmHg-s-cm, p = 0.826 and 1.9 ± 2.4 vs. 1.9 ± 1.8 times, p = 0.550, respectively); however, the patient with sub-circumferential mucosal defect had a reduction in the DCI (before, 966.4 mmHg-s-cm; after, 587.8 mmHg-s-cm) and more frequent ineffective or fragmented contractions (before, 2 times; after, 5 times) after ESD. Furthermore, the patient with circumferential mucosal defects also showed a reduction in DCI (before, 3763.0 mmHg–s-cm; after, 2110.5 mmHg-s-cm) and more frequent ineffective or fragmented contractions (before, 0 times; after, 3 times).

Although no patients had noted dysphagia before ESD, four patients, including two cases with extensive ESD, developed dysphagia after ESD (p = 0.030).

Conclusion: Although there were no statistically significant differences between esophageal function before and after ESD, an extensive ESD could affect esophageal function and result in dysphagia. In this study, the number of patients with extensive ESD was small. Therefore, a further prospective study of patients with extensive ESD would be required for definitive conclusions.

Disclosure of Interest: None declared

P1119 SAFETY OF PER-ORAL ENDOSCOPIC MYOTOMY (POEM) IN PATIENTS WITH SEVERE CO-MORBIDITIES

A. Bapaye¹, N. A. Dubale¹, K. Sheth¹, P. Desai², N. Mehta³, M. Kabrawala², R. Pujari¹, S. Date¹, J. A. Bapaye¹, M. Kulkarni¹

¹Shivanand Desai Center for Digestive Disorders , Deenanath Mangeshkar Hospital and Research Center, Pune, ²Surat Institute of Digestive Sciences, Surat, ³Vedanta Institute of Gastroenterology, Ahmedabad, India

Contact E-mail Address: amolbapaye@gmail.com

Introduction: Per-oral endoscopic myotomy (POEM) is an upcoming treatment modality for achalasia cardia. Results of POEM have been encouraging and are comparable to those after laparoscopic Heller’s myotomy (LHM) or endoscopic balloon dilatation (EBD). The patients with severe cardio-respiratory diseases are relative contraindications for LHM or EBD. In this multi-center study, we analyzed safety and efficacy of POEM in sub-group of patients with severe co-morbid conditions.

Aims & Methods: Consecutive patients with achalasia cardia confirmed on endoscopy (EGD), high-resolution manometry (HRM) and barium swallow and undergoing POEM at three centers were included. Associated co-morbidities were recorded and graded according to American Society of Anaesthesiology (ASA) classification. Eckhardt dysphagia score was recorded before and after the procedure. Procedure time, technical success and complications were noted. Follow up was by EGD, HRM at 4 weeks and subsequently monthly by telephone.

Results: 61 patients were enrolled. 18 (29.50%) had severe systemic diseases classified as ASA class 3 or 4 and were analyzed. Mean age 57.41 years and females (6). Achalasia types: I – 4, II – 14, III – nil. Median symptom duration: 54 months. Comorbid diseases: cardiac 5 (ischemic heart disease – 4, permanent pacemaker – 1), pulmonary disease – 5 (COPD- 3, interstitial lung disease – 2, thoracic empyema - 1) essential hypertension (11), diabetes mellitus (4), morbid obesity (1). 8 patients (44%) had two or more co-morbid illnesses. Mean pre- procedure Eckhardt score – 7.2 (Range 6 – 9); mean LES pressure 36.78mmHg (Range 17.5 – 68mmHg). Mean procedure duration was 117.2 minutes (50 – 270). There were no intra or post procedural complications or deaths. Post-operative hospital stay was < 48 hours for all patients. Clinical success was 100%. At 4-weeks follow up, mean Eckhardt score was 1.42 (1 – 2, p = 0.001) and mean LES pressure 10.06mmHg (4.7 – 19) (p = 0.005). At a mean 9-month follow up, mean Eckhardt score remained at 1.48 (Range 1 – 2).

Conclusion: POEM is safe and effective treatment for achalasia cardia even in patients with severe systemic diseases that may preclude surgical intervention.

Disclosure of Interest: None declared

P1120 PROTON PUMP INHIBITOR AND SELECTIVE SEROTONIN REUPTAKE INHIBITOR THERAPY FOR THE MANAGEMENT OF NON CARDIAC CHEST PAIN

K. Katopodi¹, N. Viazis¹, G. Karamanolis², J. Anastasiou¹, K. Denaxas², M. Giakoumis¹, T. Koukouratos¹, D. Kamberoglou², A. Christidou¹, S. D. Ladas², D. G. Karamanolis¹

¹Department of Gastroenterology, Evangelismos Hospital, ²Academic Department of Gastroenterology, Athens Medical School, Laiko General Hospital, Athens, Greece

Introduction: Although gastroesophageal reflux disease (GERD) constitutes the main cause of non cardiac chest pain (NCCP), administration of proton pump inhibitors (PPIs) benefits only a minority of patients. Our prospective study aimed to evaluate the effect of PPI and selective serotonin reuptake inhibitor (SSRI) therapy on the different subtypes of NCCP patients using multichannel intraluminal impedance and pH monitoring (MI-pH).

Aims & Methods: All patients with NCCP (i.e. at least 3 episodes of chest pain per week in the previous 3 months and exclusion of a cardiac source for the chest pain) underwent impedance and pH monitoring and the total distal esophageal acid exposure and the symptom index for chest pain were calculated. All patients also underwent esophageal manometry and upper endoscopy and were excluded if erosive esophagitis, Barrett’s esophagus, eosinophilic esophagitis or motility abnormalities were found. According to the results of the impedance monitoring, patients have been prescribed PPIs twice daily if abnormal distal esophageal acid exposure was noted (group A), citalopram 20mg once daily and PPI once daily if a positive symptom index for chest pain was noted (group B) and citalopram 20mg once daily if a negative symptom index for chest pain was noted (group C). In all cases therapy has been administered for 8 weeks and treatment success was defined as the complete disappearance of the chest pain.

Results: From March 2014 till March 2015, 66 patients with NCCP were screened for entry into the study. Three were excluded because of motility abnormalities during manometry (n=1) and the presence of esophagitis (n=2). Therefore the study sample consisted of 63 patients. From these patients 9 exhibited abnormal distal esophageal acid exposure and received PPIs twice daily (group A), 18 patients had a positive symptom index for chest pain and received citalopram 20mg once daily and PPI once daily (group B) and 36 had a negative symptom index for chest pain and received citalopram 20mg once daily (group C). After 8 weeks of therapy, complete resolution of chest pain was noted in 8 patients of group A (88.9%), in 13 patients of group B (72.2%) and in 24 patients of group C (66.7%).

Conclusion: Using combined impedance-pH monitoring different subtypes of non cardiac chest pain patients could be identified. According to the results of the monitoring patients can receive targeted treatment with PPIs and/or citalopram with a favorable outcome for the great majority of them.

Disclosure of Interest: None declared

P1121 SYMPTOMS AND ESOPHAGEAL MOTILITY BASED ON PHENOTYPIC FINDINGS OF PATIENTS WITH SYSTEMIC SCLEROSIS

K. Denaxas¹, K. Papaxoinis¹, S. Panopoulos², D. Kamberoglou¹, P. Sfikakis², G. Karamanolis¹

¹Academic Gastroenterology Department, ²Rheumatology unit, Athens Medical School, Athens, Greece

Contact E-mail Address: kdenaxas1@yahoo.gr

Introduction: Scleroderma esophagus is defined as esophageal disease seen in patients with known scleroderma and is characterized by distal aperistalsis and LES incompetence because of fibrosis of esophageal smooth muscle. The association between scleroderma esophagus and different subgroups of the patients with systematic sclerosis (SSc) is still conflicting.

Aims & Methods

Aim: To assesses factors (cutaneous findings, pulmonary fibrosis, cutaneous ulcers, and computed tomography (CT) findings of esophageal lumen) that are associated with the clinical presentation and esophageal motor dysfunction of scleroderma esophagus.

Methods: Fifty-four SSc patients (48 women, mean age 50.61 ± 11.67) with esophageal involvement underwent clinical interview, medical records review and high resolution manometry (HRM) in a 2-year period study. Patients completed a symptom questionnaire. CT study enrolled totally 27 patients that underwent CT of the thorax at the time of scleroderma diagnosis and thereafter measurement of the diameter of the esophageal lumen at the level of the pulmonary veins origin (normal values were considered > 9mm).

Results: On esophageal manometry, findings revealed a pattern typical of scleroderma esophagus. In the symptom questionnaire responses, the most severe symptom reported was regurgitation, while the most frequent symptom conveyed was heartburn. Between different subgroups of SSc (diffuse vs. limited type, with vs. without pulmonary fibrosis, with vs. without cutaneous ulcers) there was no statistically significant difference in the severity and frequency of esophageal symptoms and in esophageal motility. The only statistically significant difference was observed in patients with esophageal diameter <9mm in CT who reported more severe dysphagia compared to patients with esophageal diameter >9mm in CT (51.2 ± 19.5 vs. 9.7 ± 13.8, respectively, p < 0.0001 ).

Conclusion: Our results did not support the idea that patients with different investigated factors are associated with the clinical and manometric presentations of scleroderma esophagus. Dysphagia is the only symptom that associated with esophageal diameter <9mm in CT. Dysphagia is likely to attribute to progressive fibrosis of esophagus causing stenosis of esophageal lumen.

Disclosure of Interest: None declared

P1122 PRUCALOPRIDE INCREASES BASAL LES TONE IN PATIENTS WITH ESOPHAGEAL MOTILITY DISORDERS

A. Pitocco¹, L. Grossi¹, M. Di Berardino¹, A. F. Ciccaglione¹, L. Marzio¹

¹School of Gastroenterology, G d'Annunzio University of Chieti-Pescara, pescara, Italy

Contact E-mail Address: rinogrossi62@gmail.com

Introduction: Esophageal hypomotility is a frequent finding in patients with upper GI symptoms, but to date there are not pharmacological options to improve esophageal motor activity. Prucalopride(PRU) is a selective agonist for 5-HT4 receptors, used for the treatment of chronic constipation that stimulates peristalsis and colonic transit. Recent studies suggest a potential role of PRU on esophageal motility, however the data available are limited to animal models. The only evidences in humans are related to a reduced number of reflux episodes in GERD patients and a faster gastric emptying in healthy subjects.

Aims & Methods: Aim of our study has been to determine whether Prucalopride has an action on esophageal body and LES motor activity in patients affected by esophageal weak or ineffective peristalsis. Patients and methods: 6 patients (2 Male, 4 Female) undergoing esophageal High Resolution Manometry (HRM) with detection of low amplitude esophageal body contractility and/or low basal LES tone entered into the study. After basal HRM they received 2mg/day (Q. D.) of PRU half an hour before lunch for 14 days. At the end of the treatment, a second HRM was performed. Waves amplitude and duration, Distal Contractile Integral (ICD) , Basal LES tone, Integrated residual pressure (IRP), distal latency were analyzed to identify possible changes as compared to baseline.

Results: PRU was associated to an increase in basal LES tone as compared to baseline (17.8 ± 4.9 basal vs 24.5 ± 6.8 mmHg after PRU, p = 0.01), while no change of esophageal body motility was computed. No side effects were reported.

Conclusion: A short course of Prucalopride 2 mg/day leads to an increase in LES basal tone with no changes in esophageal body motility. The drug was well tolerated. These preliminary data suggest a potential role by PRU in the treatment of patients with a deranged function of the esophago-gastric barrier. Further randomized controlled studies are needed to reinforce this hypothesis.

Disclosure of Interest: None declared

P1123 HIGH RESOLUTION ESOPHAGEAL MANOMETRY WITH A STANDARDIZED TEST MEAL INCREASES DIAGNOSTIC SENSITIVITY FOR CLINICAL RELEVANT ESOPHAGEAL MOTILITY DISORDERS

M. Fox¹², D. Ang³⁴, K. Knowles⁵, J. Wright⁶, E. Tucker⁵⁷, R. Sweis⁸

¹Department of Gastroenterology, Nottingham Digestive Diseases Centre and Biomedical Research Unit, Nottingham, United Kingdom, ²Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland, ³Gastroenterology, Changi General Hospital, Singapore, Singapore, ⁴Gastroenterology, Gastroenterology and Hepatology, Zurich, Switzerland, ⁵Department of Academic Surgery, Nottingham University Hospitals, Nottingham, United Kingdom, ⁶Department of Academic Surgery, Nottingham University Hospitals, Nottingham, Switzerland, ⁷Gastroenterology and Hepatology, Nottingham Digestive Diseases Centre and Biomedical Research Unit, Nottingham, ⁸Department of Gastroenterology, University College London, London, United Kingdom

Contact E-mail Address: Daphne_ang@cgh.com.sg

Introduction: The Chicago Classification (CC) for esophageal motility disorders using high resolution manometry (HRM) is the accepted standard for the diagnosis of disorders of esophageal motility and is based on the analysis of ten 5ml water swallows (WS). It is uncertain if WS are representative of esophageal dysfunction during normal drinking and eating. Indeed, most patients do not receive any explanation for their symptoms with the current standards of using WS alone. Recent papers demonstrate a high rate of symptomatic dysmotility during solid test meal (STM) in patients with proton pump inhibitor (PPI) resistent reflux disease ¹ and symptomatic dysphagia post-fundoplication.²

Aims & Methods: The primary aim was to compare the frequency of major and minor esophageal motility disorders using WS and STM. The secondary aim was to determine if observations during STM can establish esophageal dysfunction as a cause of dysphagia. Prospective series of patients referred for esophageal HRM between January 2010 and December 2013. WS and STM HRM studies were performed in the upright, seated position. Diagnosis of major and minor esophageal motility disorders were based on CC version 3.0 for water swallows³ modified for use with solid swallows/test meal as appropriate ¹.

Results: 750 consecutive patients (44% male; age 52.5 ± 16.9 years) referred for dysphagia (n=360 [48%]), reflux symptoms (n=329 [44%]) and other indications (n=61 [8%]) were studied. Major esophageal motility disorders were present in 163/750 (22%) WS and 321/750 (43%) STM studies (p < 0.001). Conversely, we observed a matching decrease in the proportion of patients with minor esophageal motility disorder diagnosed with STM [152/750 (20%) compared to WS [335/750 (45%) (p < 0.001)]. Additionally, whereas symptoms were rare with WS (<1%), close association of dysphagia with dysmotility during STM established the clinical relevance of HRM findings in 245/360 (68%) patients. Patients with major motility disorders were more likely to have dysphagia associated with dysfunction than those with minor motility disorders or normal HRM findings (64% v. 26% v.13%; p < 0.001). The most common major dysmotility disorder detected by STM that were missed by WS was outlet obstruction, followed by spasm and hypercontractile dysmotility.

Conclusion: STM increases the diagnostic yield of treatable, major dysmotility by HRM studies compared to water swallows and can establish the association between esophageal dysfunction and symptoms.

Disclosure of Interest: M. Fox Financial support for research: Given Imaging, Lecture fee(s): Given Imaging; MMS; Sandhill, Consultancy: Given Imaging; Mui Scientific, D. Ang: None declared, K. Knowles: None declared, J. Wright: None declared, E. Tucker: None declared, R. Sweis Financial support for research: Given Imaging, Lecture fee(s): Given Imaging

P1124 INCIDENCE AND PREVALENCE OF EOSINOPHILIC ESOPHAGITIS IN CHILDREN AND ADULTS IN POPULATION-BASED STUDIES: A SYSTEMATIC REVIEW AND META-ANALYSIS

A. J. Lucendo¹, I. Pérez-Martínez², Á. Arias³

¹Gastroenterology, Hospital General de Tomelloso, Tomelloso, ²Gastroenterology, Hospital General Universitario Central de Asturias, Oviedo, ³Research Support Unit, Hospital General La Mancha Centro, Alcázar de San Juan, Spain

Contact E-mail Address: alucendo@vodafone.es

Introduction: In recent years several studies have attempted to define the extent of EoE from estimating its epidemiology in different populations, by using different methodological approaches, from population-based studies to others that defined the frequency of EoE in series of endoscopies and esophageal biopsies. Although the results are widely variable, a trend to gradual increase in the prevalence of EoE has been described in recent years according to figures provided by different authors. However, the epidemiology of EoE and its temporal trends in population-based studies have not been systematically evaluated to date, which prevents us to reliably and accurately estimate the magnitude of the problem.

Aims & Methods: A systematic review and meta-analysis was conducted to provide an accurate estimate of incidence and prevalence rates of eosinophilic esophagitis (EoE).

We search MEDLINE, EMBASE, and SCOPUS databases for population-based studies dealing with the epidemiology of EoE. The pooled incidence and prevalence rates, male-to-female and children-to-adult rate ratios, and geographical and temporal variations were calculated using a fixed or random-effects model.

Results: The search yielded 1,334 references; the final quantitative summary included 13 population-based studies from North America, Europe, and Australia, with the results showing high heterogeneity. The pooled EoE incidence rate was 4.8/100,000 persons/year (95% confidence interval [CI] 2.8–7.2) and was higher for adults (7; 95%CI 1–18.3) than for children (5.1; 95%CI 1.5–10.9).

The pooled prevalence of EoE was 24.7 cases/100,000 inhabitants (95%CI 15.3–36.2), rising to 32.7 (95%CI 18.4–51) in studies with a lower risk of bias. The prevalence was higher in adults than in children (43.4; 95%CI 22.5–71.2 vs. 29.5; 95%CI 17.5–44.7, respectively), and in American compared to European studies.

A steady rise in EoE incidence and prevalence rates was observed upon comparison of studies conducted before and after 2008. No significant publication bias was found.

Conclusion: EoE is a common disease that has significantly increased in North America and Europe in the last years. The population-based incidence and prevalence of EoE vary widely across individual studies, potentially because of variations in ascertainment of cases between centers and quality of research. Further large multicenter prospective research is needed to evaluate reported data.

Disclosure of Interest: None declared

P1125 NON-INVASIVE BIOMARKERS FOR MONITORING RESPONSE TO SHORT-TERM TREATMENT WITH BUDESONIDE IN EOSINOPHILIC ESOPHAGITIS

C. Schlag¹, A. Heiseke², K. Brockow³, M. Bajbouj¹, A. Krug², U. von Arnim⁴, A. Straumann⁵, M. Vieth⁶, C. Bussmann⁷, R. Mueller⁸, R. Greinwald⁸, S. Miehlke⁹

¹2nd Medical Department, Technical University, ²Institute for Immunology, LMU München, ³Klinik für Dermatologie und Allergologie am Biederstein, Technical University, Munich, ⁴Department of Gastroenterology & Hepatology, University Hospital Magdeburg, Magdeburg, Germany, ⁵Swiss EoE Research Network, Olten, Switzerland, ⁶Institute for Pathology, Klinikum Bayreuth, Bayreuth, Germany, ⁷Institute for Pathology, Kantonsspital Luzern, Luzern, Switzerland, ⁸Dr. Falk Pharma GmbH, Freiburg, ⁹Centre for Digestive Diseases Eppendorf, Hamburg, Germany

Contact E-mail Address: Christoph.Schlag@lrz.tum.de

Introduction: In eosinophilic esophagitis (EoE), treatment response is usually monitored by histological assessment of the esophagus, which requires repeated upper endoscopy. Instead, non-invasive biomarkers would be valuable. We thus examined absolute eosinophil count (AEC) and serum levels of Chemokine (C-C motif) ligand (CCL)-17, CCL-18, CCL-26, eosinophil cationic protein (ECP) and mast cell tryptase (MCT) for their utility to monitor treatment response in adult EoE-patients.

Aims & Methods: Venous blood samples of EoE-patients (n=69) who had randomly received 14 days’ treatment with budesonide (n=51) or placebo (n=18) were analysed. AEC and serum-CCL-17, -CCL-18, -CCL-26, -ECP and –MCT were measured before and after treatment and were correlated to patients’ dysphagia score, endoscopy score and histological esophageal eosinophil density.

Results: Histological remission was achieved in 98% of the budesonide and 0% of the placebo recipients. AEC (380.2 vs. 214.7/cmm, P=0.0001) and serum levels of CCL-17 (294.3 vs. 257.9 pg/ml, P=0.0019), CCL-26 (26.7 vs. 16.2 pg/ml, P=0.0058), ECP (45.5 vs. 27.5 µg/l, P=0.0016) and MCT (5.3 vs. 4.5 µg/l, P=0.0019) significantly decreased in budesonide, but not in the placebo recipients. There was no significant change of serum-CCL18. Only AEC significantly correlated with esophageal eosinophil density before (r=0.28, P=0.0236) and after (r=0.42, P=0.0004) budesonide treatment.

Conclusion: Response to short-term budesonide treatment of EoE can be reflected by AEC as well as by serum marker levels of CCL-17, CCL-26, ECP and MCT. AEC seems to be most valuable, being the only marker, which shows correlation to esophageal eosinophil density.

Disclosure of Interest: C. Schlag Financial support for research: Falk Pharma, Lecture fee(s): Given Imaging, A. Heiseke: None declared, K. Brockow: None declared, M. Bajbouj Lecture fee(s): Falk Foundation, A. Krug: None declared, U. von Arnim Conflict with: Falk Pharma, Abbvie, MSD, Takeda, NPS, A. Straumann Consultancy: Falk Pharma, Conflict with: Actelion, AstraZeneca, Aptalis, GSK, Nestle, Novartis, Pfizer, M. Vieth Lecture fee(s): Falk Foundation, C. Bussmann: None declared, R. Mueller Conflict with: Employee of Falk Pharma, R. Greinwald Conflict with: Employee of Falk Pharma, S. Miehlke Conflict with: Falk Pharma, Aptalis, Olympus, Schwabe, Shire

P1126 PREDICTING ENDOSCOPIC AND HISTOLOGIC REMISSION IN ADULT PATIENTS WITH EOSINOPHILIC ESOPHAGITIS USING THE EESAI PRO SCORE

E. Safroneeva¹, M. Coslovsky¹, R. Panczak¹, M. Zwahlen¹, N. Haas¹, C. Kuehni¹, C. Bussmann², A. Straumann³, A. Schoepfer⁴, on behalf of Eosinophilic Esophagitis Activity Index Study Group

¹University Hospital Bern, Bern, ²Pathology Institute Viollier, Basel, ³EoE clinic Olten, Olten, ⁴University Hospital Lausanne / CHUV , Lausanne, Switzerland

Contact E-mail Address: alain.schoepfer@chuv.ch

Introduction: Long-standing eosinophilic esophageal inflammation leads to stricture formation with the inherent risk of food bolus impactions. It is currently unknown if clinicians can rely purely on symptom severity to estimate the endoscopic and histologic activity.

Aims & Methods: We aimed to evaluate the relationship between symptoms, endoscopic and histologic activity. Adult EoE patients were prospectively included (clinicaltrials.gov NCT00939263). Patients completed validated Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcomes (PRO) instrument that measures symptom severity (7-day recall period). The EEsAI PRO score ranges from 0-100 points. A score from 0-20 points was defined as clinical remission. Patients underwent endoscopy with esophageal biopsy sampling. Endoscopic findings were recorded according to the Endoscopic Reference Score (EREFS). Endoscopic remission was defined as follows: 1) absence of white exudates; 2) absence of moderate and severe rings; 3) absence of strictures; 4) furrows and edema could be present but not in combination. Histologic inflammatory remission was defined as ≤5 eosinophils/high power field (hpf).

Results: A total of 120 adult EoE patients were recruited (61% males, 95% Caucasians, EoE symptom onset >5 years in 67.2%). Fifty-one patients (42.5%) were in clinical remission. The following frequency of endoscopic findings was found: 13/51 (25.5%) patients had white exudates, 25/51 (49%) had furrows, 24/51 (47.1%) had edema, 23/51 (45.1%) had mild rings, 8/51 (15.7%) had moderate rings, 6/51 (11.8%) had a low grade stricture, and 1/51 (2%) had an intermediate stricture (passage of 8-9 mm-outer diameter endoscope not possible). Histologic remission was found in 23/51 (45.1%) of patients, 8/51 (15.7%) had 6-20 eos/hpf, 14/51 (27.5%) had 21-100 eos/hpf, and 6/51 (11.8%) had >100 eos/hpf. Only 4/51 (7.8%) patients had eosinophilic microabscesses. Of the 51 patients in clinical remission 25 patients (49%) were in endoscopic remission and 23 patients (45.1%) were in histologic remission. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of a PRO score ≤20 points to predict endoscopic remission were 64%, 68%, 49%, 80%, 67%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of a PRO score ≤20 points to predict histologic remission were 54%, 64%, 45%, 71%, 60%, respectively.

Conclusion: The EEsAI PRO score with a definition of ≤20 points for clinical remission has a moderate overall accuracy in predicting endoscopic and histologic remission. Thus, in addition to assessing PRO measures, assessment of objective signs of disease activity, including endoscopic and histologic alterations, remains to be an important element in the judgment of overall disease activity.

Disclosure of Interest: None declared

P1127 MODULATION OF CD8+ CELLS INFILTRATION AND ACTIVITY IN EOSINOPHILIC OESOPHAGITIS BY SIX-FOOD ELIMINATION DIET

M. Fortea¹, A. Lucendo², A. Arias³, A. M. González-Castro¹, D. Guagnozzi¹, F. Azpiroz¹⁴, C. Alonso-Cotoner¹⁴, J. Santos¹⁴, M. Vicario¹⁴

¹Neuro-immuno-gastroenterology Laboratory, Digestive Disease Research Unit. Department of Gastroenterology, Hospital Universitario Vall d’Hebron. Vall d’Hebron Institut de Recerca, Barcelona, ²Hospital General de Tomelloso, ³Hospital General de la Mancha Centro, Ciudad Real, ⁴Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd, Barcelona, Spain

Contact E-mail Address: marinaforgui@gmail.com

Introduction: Eosinophilic oesophagitis (EoE) is an inflammatory disease of the esophagus histologically characterized by an infiltration of intraepithelial eosinophils. Clinical improvement and histological normalization through an exclusion diet support an allergic origin. However, similarities in the oesophageal transcriptome between allergic and non- allergic patients and the increase in intraepithelial CD8⁺ leucocytes suggest the existence of additional mechanisms in the pathogenesis of EoE.

Aims & Methods: To identify the role of CD8⁺ population in the pathophysiology of EoE.

EoE patients (n=10; age: 33 ± 10 years old) who responded clinically and histologically to a six-food elimination diet (SFED: milk, wheat, egg, fish, legumes, nuts) and healthy controls (C, n=10; age: 53 ± 20 years old) were selected. Clinical symptoms were assessed by a non-validated score and analysed before and after SFED, and food triggers were identified. The number of eosinophils per high power field (hpf) was quantified after haematoxylin and eosin stainning in oesophageal biopsies of the C group and in the EoE group before and after SFED. The number of CD8⁺ and CD2⁺ cells was quantified by area (mm²). Furthermore, gene expression of specific CD8 molecules (granzyme A, granzyme B and granulysin) and of mucosal migration molecules (α4-integrin and MADCAM1) was evaluated by quantitative RT-PCR in esophageal biopsies of all subjects.

Results: The main symptoms reported by patients were dysphagia (100%), and food impaction (50%). Diet significantly reduced clinical symptoms in all patients. Milk was identified as the trigger food in 50% of the patients. Oesophageal epithelium of EoE patients presented greater eosinophil (EoE:63 ± 40; C:0/hpf), CD8⁺ (EoE:512 ± 360; C:84 ± 50/mm²), CD2⁺ (EoE:591 ± 342; C:108 ± 50/mm² ) and CD8⁺CD2⁺ (EoE:480 ± 356; C:79 ± 49/ mm²) counts than those in group C (P < 0.05). SFED significantly reduced the magnitude of these populations to C values in parallel with the clinical improvement of patients. Gene expression of cytotoxic molecules and markers of cell migration was higher in EoE than in C (1.6 to 26 fold-change; P < 0.05) and significantly decreased to C values after SFED treatment.

Conclusion: Reduction of CD8⁺ number and activity, in association with clinical improvement after SFED, suggest that active cytotoxic mechanisms are present in the oesophageal epithelium and contribute to the physiopathology of EoE.

Disclosure of Interest: None declared

P1128 THE GERDQ QUESTIONNAIRE DISTINGUISHES PROTON PUMP INHIBITOR-RESPONSIVE ESOPHAGEAL EOSINOPHILIA FROM EOSINOPHILIC ESOPHAGITIS PATIENTS

O. Bartolo¹, S. Tolone², C. de Cassan¹, R. Caccaro¹, F. Galeazzi¹, L. Nicoletti¹, R. Salvador¹, M. Costantini¹, E. Savarino¹

¹Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, ²Department of Surgery, Second University of Naples, Naples, Italy

Introduction: Eosinophilic esophagitis (EoE) and Proton Pump Inhibitor-response esophageal eosinophilia (PPI-REE) present similar phenotypic appearance, similar histopathology but different response to antisecretory therapy. Indeed, current studies failed to observe clinical features able to distinguish the two entities. However, previous investigations did not systematically assess reflux-related symptoms by means of validated questionnaires. Recently, the GerdQ questionnaire has been validated in comparison with endoscopy and/or pH-testing for the diagnosis of gastro-oesophageal reflux disease (GERD).

Aims & Methods: We aimed to apply GerdQ questionnaire in patients with EoE and PPI-REE to assess whether a prospective and systematic evaluation of reflux symptoms may be helpful to distinguish patients with PPI-REE from those with EoE. Consecutive patients diagnosed with EoE and PPI-REE according to international criteria [a) presence of at least one typical symptom of esophageal dysfunction; b) at least 15 eosinophils per high-power field at mid/proximal esophagus; c) persisting or nor of eosinophils at mid/proximal esophagus after an 8-week PPI trial] prospectively completed a specific GERD-related questionnaire (GERDQ). The GerdQ questionnaire is a simple, self-administered and patient-centered questionnaire including six items¹. A cut-off value higher ≥ 9 (range of 0–18) was considered diagnostic for GERD. For comparisons, a group of 27 patients with proven reflux disease was used.

Results: Fifty-two consecutive patients with histologically-detected eosinophilic infiltration (>15 eos/hpf) at mid-proximal oesophagus and with symptoms of esophageal dysfunction were included in the study. At the follow-up endoscopy plus biopsy, after 8 weeks treatment with twice-daily PPI, thirty-five (67%) patients were identified as having EoE, whereas 17 (33%) patients were diagnosed with PPI-REE. The two cohorts had similar dysphagia for solids (EoE 74% vs. PPI-REE 76%, p = 0.651), bolus impaction (66% vs. 70%, p = 0.655), but different heartburn (26% vs. 70%, p < 0.001), regurgitation (17% vs. 41%, p = 0.014) and chestpain (20% vs. 41%, p = 0.012). The overall GerdQ score was statistically lower in EoE vs. PPI-REE [1 (0-6) vs. 8 (2.5-11.25), p = 0.004]. When compared to control patients with GERD, both EoE and PPI-REE patients showed increased rate in dysphagia parameters, whereas EoE individuals reported less frequently heartburn (26% vs. 85%, p = 0.001), regurgitation (17% vs. 74%, p = 0.001) and overall GerdQ scores [1 (0-6) vs. 8 (6-12), p =  0.001] than control patients with GERD. In contrast, no difference was found comparing PPI-REE and control patients with GERD for heartburn, regurgitation and overall GerdQ score (p = 0.176, 0.192 and 1.000, respectively). Two EoE patients (6%), 8 PPI-REE patients (47%) and 15 control patients with GERD (55%) had a total score equal or above 9 (EoE vs. PPI-REE p = 0.0001, EoE vs. GERD p = 0.002 and PPI-REE vs. GERD p =  0.757).

Conclusion: The GerdQ is a useful complementary tool to distinguish patients with PPI-REE from those with EoE. The implementation of GerdQ could reduce the need for more aggressive therapies (i.e. topical steroids and specialised diets) and improve resource utilisation.

Disclosure of Interest: O. Bartolo: None declared, S. Tolone: None declared, C. de Cassan: None declared, R. Caccaro: None declared, F. Galeazzi: None declared, L. Nicoletti: None declared, R. Salvador: None declared, M. Costantini: None declared, E. Savarino Lecture fee(s): Given Imaging

P1129 MOTILITY ABNORMALITIES IN PATIENTS WITH EOSINOPHILIC ESOPHAGITIS

U. von Arnim¹, A. Kandulski¹, O. Levkovic¹, J. Weigt¹, P. Malfertheiner¹

¹Gastroenterology, Hepatology and Infectious Diseases, Otto- von Guericke University, Magdeburg, Magdeburg, Germany

Contact E-mail Address: ulrike.vonarnim@med.ovgu.de

Introduction: Patients (pat.) with eosinophilic esophagitis (EoE) often present with dysphagia and bolus obstruction. Whereas previous investigations using conventional manometry showed no significant changes, data about motility patterns from high resolution manometry (HRM) are rare.

Aims & Methods: To investigate motility patterns of pat. with EoE using HRM in correlation with clinico-pathological subtypes and in comparison controls without dysphagia and normal findings in HRM.

26 (10 female, 16 male, median age: 46.2 range 24-72 years) EoE pat. were included and investigated endoscopically, histopathologically and by HRM while on PPI medication. Diagnosis of EoE was confirmed according to the consensus guidelines 2011. HRM was performed in the upright position according to the Chicago classification system using 10 ml swallows.

26 controls were included (7 female, 19 male, median age: 51.0; range 22-78 years) from the GI lab database. Reason for HRM investigations was mainly clinically suspected GERD. Pat. with large hiatal hernia (>1.5 cm) were excluded. Results from HRM analysis were further correlated with the clinico-pathological EoE subtype (inflammatory (n=17) vs. fibrotic (n=9)).

Results: Pat. with EoE presented with significant higher resting pressure of the lower esophageal sphincter (LES) and upper esophageal sphincter (UES) (LES 34.0 vs. 26.3 mmHg, p < 0.01; UES: 160.3 vs. 98.3 mmHg, p <0.01) compared with the control group. Further, pat. with EoE frequently showed larger breaks in the 20 mmHg isobaric contour (breaks 20 mmHg 2.5 vs. 0.7 cm, p = 0.03). Differences were seen especially within breaks according to the transition zone and to the middle of the peristaltic wavefront (breaks 20 mmHg transition zone 1.2 vs 0.5 cm, p < 0.01; breaks 20 mmHg middle 0.8 vs. 0.5 cm, p < 0.01. Larger breaks in the transition zone and in the middle of the peristaltic wavefront were also seen in the 30 mmHg isobaric contour by in pat. with EoE (breaks 30 mmHg 2.3 vs. 1.5 cm, p = 0.01; breaks 30 mmHg middle 1.1 vs. 0.3 cm, p < 0.01). These findings were not associated with a specific clinico-pathological subtype of EoE. For other parameters of HRM (IRP4s, intrabolus pressure, distal contractile integral, contractile front velocity, distal latency) no significant changes were found in pat. with EoE.

According to the Chicago classification system, the diagnosis in HRM varies between normal appearance (n=11) to hypomotility (n=10) and EGJ outflow obstruction (n=5).

Conclusion: Esophageal motor dysfunction is a common phenomenon in pat. with EoE. Breaks of the contractile integrity with hypomotility and impaired bolus transit might explain the appearance of dysphagia in these pat., independant from clinico-pathological subtype.

Disclosure of Interest: U. von Arnim Lecture fee(s): Dr. Falk Pharma, Abbvie, MSD, A. Kandulski Lecture fee(s): Allmiral, O. Levkovic: None declared, J. Weigt Lecture fee(s): Fuji, P. Malfertheiner Lecture fee(s): Dr. FalkPharma, Abbvie, Aptalis

P1130 THE PREVALENCE OF GASTROESOPHAGEAL REFLUX DISEASE IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS IN KOREA

C. M. Lee¹, D. H. Lee¹, J. J. Hwang¹, H. Yoon¹, C. M. Shin¹, Y. S. Park¹, N. Kim¹

¹Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Korea, Republic Of

Contact E-mail Address: gyrzax@gmail.com

Introduction: In the western population, gastroesphageal reflux disease (GERD) is highly prevalent in patients with idiopathic pulmonary fibrosis (IPF). It has been hypothesized that chronic microaspiration due to GERD may cause repetitive subclinical injury to the lung leading to pulmonary fibrosis. Although some studies suggest proton pump inhibitor (PPI) was associated with slower decline of forced vital capacity (FVC), fewer acute exacerbation, decreased radiologic fibrosis and longer survival time in patients with IPF, these effects of PPI remain unclear.

Aims & Methods: The aims of this study were to investigate the prevalence of GERD in patients with IPF in Korean population and evaluate the relation with IPF and GERD or PPI. We retrospectively reviewed a chart of 917 consecutive adult patients with IPF at Seoul National University Bundang Hospital between April 2003 and March 2015.

Results: Mean age ± standard deviation (SD) was 75.5 ± 22.7 years, and 662 (72.2%) were males. Mean duration of follow up was 2.6 ± 2.8 years. Of the 917 patients with IPF, 145 (15.8%) were diagnosed with GERD. Of these 145 patients with GERD, 38 (26.2%) were diagnosed with erosive reflux disease by mucosal breaks and 107 (73.8%) had typical heartburn and/or acid regurgitation with minimal change or normal finding on esophagogastroscopy. In the univariate and multivariate COX regression harzard model, GERD (HR, 0.51; 95% CI, 0.28 – 0.94; P = 0.030), including azathioprine (HR, 1.71; 95% CI, 1.05 – 2.77; P = 0.030), age (HR, 1.04; 95% CI, 1.02 – 1.06; P = 0.001), initial FVC (HR, 0.98; 95% CI, 0.97 – 0.99; P = 0.001), hypertension (HR, 0.45; 95% CI, 0.27 – 0.76; P = 0.003) and pulmonary hypertension (HR, 4.48; 95% CI, 1.06 – 18.89; P = 0.041) was significantly associated with IPF-related mortality. However, there was an inversely association between GERD and IPF-related mortality. In the multivariate logistic regressive analysis, PPI (OR, 1.51; 95% CI, 1.00 – 2.28; P = 0.048), including peptic ulcer (OR, 1.71; 95% CI, 1.01 – 2.88; P = 0.046), prednisolone (OR, 1.64; 95% CI, 1.10 – 2.44; P = 0.015), N-acetylcysteine (OR, 2.32; 95% CI, 1.66 – 3.23; P < 0.001), initial FVC (OR, 1.03; 95% CI, 1.02 – 1.04; P < 0.001) and period of follow up (OR, 1.09; 95% CI, 1.02 – 1.15; P = 0.006) was associated with the aggravation of FVC. In a subgroup of patients with GERD and no history of peptic ulcer, PPI was also significantly associated with the aggravation of FVC (OR, 1.91; 95% CI, 1.32 – 2.76; P = 0.001).

Conclusion: In Korean patients with IPF, the prevalence of GERD was relatively lower than in western. Conversely, the IPF related mortality rate was significantly lower in patients with GERD than in patients without GERD. In contrast to prior researches, PPI maybe has no protective effect for aggravation of lung function and mortality.

Disclosure of Interest: None declared

P1131 WHAT IS THE FREQUENCY AND IMPACT OF GER AND MOTILITY DISORDERS IN COPD EXACERBATIONS?

S. Iliaz¹, R. Iliaz², S. T. Onur³, S. Arıcı², U. Akyuz⁴, C. Karaca², K. Demir², F. Besisik², S. Kaymakoglu², F. Akyuz²

¹Departmant of Pulmonology, Koç University Hospital, ²Gastroenterology, I.U. Istanbul medical faculty, ³Department of Pulmonology, Yedikule Chest Disease and Thoracic Surgery Education and Research Hospital, ⁴Gastroenterology, Fatih Sultan Mehmet Educational and Research Center, Istanbul, Turkey

Contact E-mail Address: filizakyuz@hotmail.com

Introduction: Gastro-esophageal reflux disease (GERD) has been shown to worsen asthma control. But, the relationship between chronic obstructive pulmonary disease (COPD) exacerbations and GERD is less investigated, and there are conflicting results in literature.

Aims & Methods: We aimed to evaluate the presence of GERD and its symptoms in patients with COPD, and its impact on frequent exacerbation of COPD. We included 24 patients with stable mild-moderate stage COPD and 19 healthy volunteers as the control group. The patients using anti-reflux medication, non-invasive mechanical ventilation, and having acute exacerbation of COPD during previous 4 weeks were excluded. To all patients, we applied GERD symptom questionnaire, gastroscopy, high-resolution manometry (HRM) and ambulatory 24-hour pH-impedance study.

Results: Out of 24 patients with COPD, 23 were male. In control group, there were 12 male (p = 0.14). The mean age of the patients with COPD was 63 ± 10 years and 44 ± 10 years for the controls (p < 0.001). According to GERD questionnaire, only 5 (21.7%) patients had typical GERD symptoms. According to 24-hour pH-impedance study, mean DeMeester score was 38.1 in COPD group and 13.3 in the control group (p = 0.005). Seventeen (73.9%) patients in COPD group versus 5 (26.3%) patients in control group had pathologic acid reflux (p = 0.002). Symptom association probability (SAP) positivity rate was 17.4% (n=4) in COPD group and none of the controls had SAP positivity (p = 0.11). Mean proximal extent rate of reflux (Z 17.cm) was 26.4 ± 12 % in COPD group. According to motility results, only 2 (20%) patients in the control group had minor motility disorder, the remainder was normal. On the contrary, 17 (70.8%) patients in COPD group had minor motility disorder, and 4 (16.7%) patients had major motility disorder (p = 0.001). Three (12.5%) patients in the COPD group were normal. In COPD group, 14 (58.3%) patients had weak peristalsis with large defects, 3 (12.5%) patients had weak peristalsis with small defects, 2 (8.3%) patients had jack hammer disorder, and 2 (8.3%) had distal esophageal spasm. Proximal extent of reflux was positively correlated with total number of exacerbation of COPD during a year time (p = 0.039, r=0.443). Seven patients (30.4%) experienced frequent exacerbations of COPD in the previous year.

Conclusion: Gastroesophageal reflux is frequent in COPD, but only a qaurter of them did have typical reflux symthoms. Motility disorders and GERD was more common in COPD group compared with the controls. Proximal extent of reflux may trigger frequent exacerbation of COPD.

Disclosure of Interest: None declared

P1132 CHANGES IN BODY MASS INDEX ARE ASSOCIATED WITH RESOLUTION OF EROSIVE ESOPHAGITIS: A 5-YEAR RETROSPECTIVE COHORT STUDY

K. B. Bang¹², J. H. Park¹, W. K. Jeon¹, D. I. Park¹, Y. S. Jung¹, C. I. Sohn¹

¹Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, ²Internal Medicine, Dankook University College of Medicine, Cheonan, Korea, Republic Of

Contact E-mail Address: kibaebang@gmail.com

Introduction: Obesity has been recognized as a risk factor for gastroesophageal reflux disease (GERD) and several studies demonstrated positive association between the body mass index (BMI) and GERD symptoms. However, literatures on whether BMI is related to the erosive esophagitis are scant.

Aims & Methods: This study aimed to investigate the effect of BMI changes on the erosive esophagitis. A retrospective cohort study was performed to assess the natural course of erosive esophagitis according to the changes in BMI. A total of 1126 cases of erosive esophagitis were included in this study. The degree of erosive esophagitis was measured by esophagogastroduodenoscopy and serially checked during the follow up period. A Cox proportional hazards model was used to investigate the hazard ratios (HRs).

Results: Of the total 1126 subjects, 906 (80.5%) cases were classified as LA-A, 209 (18.6%) as LA-B, and 11 (1%) as LA-C or LA-D at baseline. During the 5.6 years of mean follow up period, 645 (57.3%) cases showed resolution of erosive esophagitis. Subjects with decreased BMI were associated with resolution of erosive esophagitis compared to those with increased BMI (Hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.02-1.39). Even after adjusting for sex, age, smoking, alcohol consumption, fatty liver status, level of education, and physical activity, the association between the BMI and erosive esophagitis was not attenuated (HR 1.22, 95% CI 1.01-1.46).

Conclusion: Decreasing BMI was significantly and independently associated with resolution of erosive esophagitis.

Disclosure of Interest: None declared

P1133 RISK OF ACUTE MYOCARDIAL INFARCTION IN PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE: A NATIONWIDE POPULATION-BASED STUDY

W.-Y. Lei¹, J.-H. Wang², C.-H. Yi¹, X.-S. Hung¹, T.-T. Liu¹, C.-L. Chen¹

¹Department of Medicine, ²Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, Province of China

Contact E-mail Address: aquarious@seed.net.tw

Introduction: Gastroesophageal reflux disease (GERD) is a common disease which can cause troublesome symptoms and affect quality of life. In addition to esophageal complications, GERD may also be a risk factor for extra-esophageal complications. Both GERD and coronary artery disease can cause chest pain and frequently co-exist. A link between the two diseases has been suggested. However, the association between GERD and acute myocardial infarction (AMI) remain unclear.

Aims & Methods: The purpose of the study was to investigate the incidence of acute myocardial infarction in GERD patients and to compare it with that in an age- and sex-matched general population free of GERD. We also investigate the association between the risk of myocardial infarction and the use of acid suppressing agents in the cohort of GERD patients.

We identified patients with GERD from the Taiwan National Health Insurance database. The study cohort comprised 57,189 newly diagnosed GERD patients; 271,862 randomly selected age-, gender-, comobidity-matched subjects comprised the comparison cohort. Patients with any known prior coronary or peripheral arterial disease were excluded. Incidence of new AMI was studied in both groups.

Results: A total 1236 (0.5%) of the patients from the control group and 371 (0.7%) patients from the GERD group experienced AMI during years of follow-up. After Cox proportional-hazard model analysis, GERD was independently associated with increased risk of developing AMI (hazard ratio, 1.48; 95% confidence interval, 1.31–1.66, p < 0.001). Within the GERD group, subjects who were prescribed proton pump inhibitors (PPIs) for more than one years had decreased the risk of developing AMI, compared with those without taking PPIs (hazard ratio, 0.57; 95% confidence interval, 0.31–1.04, p =  0.066).

Conclusion: The large population-based study demonstrates an association between GERD and future development of acute myocardial infarction. Further prospective studies are needed to evaluate if anti-reflux medication may reduce the occurrence of acute ischemic event in GERD patients.

Disclosure of Interest: None declared

P1134 REFLUX ESOPHAGITIS IS POSITIVELY CORRELATED WITH FUNDIC GLAND POLYPS——A CASE-CONTROL STUDY

Y. Wang¹, L. Lin², L.-Y. Zhou¹, S.-R. Lin¹

¹Peking University Third Hospital, ²Beijing Shijitan Hospital, Beijing, China

Contact E-mail Address: pksunking@live.cn

Introduction: Fundic gland polyps (FGPs) is the most common type of gastric polyps, and was associated with chronic proton pump inhibitor (PPI) therapy. Most patient receive long-term PPI because of GERD, so whether FGPs is associated with PPI or GERD itself is a question.

Aims & Methods: This study aimed to elucidate the correlation between FGPs and GERD.

This case-control study included patients with FGPs (cases) and those without FGPs (controls). Consecutive patients (≥16 years of age) who agreed to complete a self-reported questionnaire and then undergo an upper endoscopy were enrolled. Patients who had undergone proton pump inhibitor (PPI) treatment for >8 weeks, had a history of familial adenomatous polyposis (FAP), or did not undergo the biopsy were excluded. The risks of sex, age, reflux symptoms, Helicobacter pylori infection, non-atrophic gastritis, reflux esophagitis, peptic ulcer disease, or upper gastrointestinal malignancy were assessed (odds ratio [OR] and its corresponding 95% confidence interval [CI]).

Results: A total of 4,250 patients were analyzed, including 288 with FGPs (cases) and 3,962 (controls) without FGPs. The patients with sporadic FGPs had an OR of 2.178 (95%CI, 1.613-2.941, P < 0.001), 1.037 (95%CI, 1.027-1.046, P < 0.001), 1.039 (95%CI, 0.998-1.082, P=0.065), 0.970 (95%CI, 0.713-1.321, P=0.848), 0.197 (95%CI, 0.121-0.321, P < 0.001), 1.993 (95%CI, 1.498-2.651, P < 0.001), 1.451 (95%CI, 1.031-2.043, P=0.033), 0.782 (95%CI, 0.410-1.491, P=0.455), and 0.265 (95%CI, 0.036-1.953, P=0.192) for female gender, advanced age, BMI, GerdQ score ≥ 8, H. pylori infection, non-atrophic gastritis, reflux esophagitis, peptic ulcer disease, and upper gastrointestinal malignancy, respectively.

Conclusion: Reflux esophagitis is positively correlated with FGPs development. Female gender, advanced age, and non-atrophic gastritis are all risk factors of FGPs development. H. pylori infection is negatively correlated with FGPs development.

Disclosure of Interest: None declared

P1135 TUMOR MICROENVIRONMENT IN ESOPHAGEAL ADENOCARCINOMA: NUCLEAR P53 OVER-EXPRESSION IS ASSOCIATED TO LOW LYMPHOCYTE ACTIVATION

M. Scarpa¹, A. Kotsafti¹, M. Scarpa¹, M. Cagol¹, R. Alfieri¹, L. Saadeh¹, M. Rugge², I. Castagliuolo³, C. Castoro¹

¹Oncological Surgery Unit, Veneto Institute of Oncology (IOV-IRCCS), ²Dept of Medicine, ³Dept of Molecular Medicine, University of Padova, Padova, Italy

Contact E-mail Address: marcoscarpa73@yahoo.it

Introduction: Esophageal adenocarcinoma (EAC) microenvironment is characterized by lack of cytokines with anti-cancer effect and by high expression of immuno-suppressive factors. HER2 over-expression is associated to worse prognosis in esophageal adencarcinoma and it is related to the depth of invasion, nodal and distant metastasis. Similarly, p53 overexpression is associated to poor disease free and overall survival.

Aims & Methods: Our aim was to evaluate the possible relationships between HER2 and p53 overexpression in esophageal cancer and the antigen presenting cells (APC) and lymphocyte function in esophageal cancer.

Mucosa samples from cancer and from healthy esophagus were obtained during esophagectomy from 64 adenocarcinoma. Frozen samples were analysed with Real Time qPCR for costimulatory molecules (Cd80, Cd86), and lymphocytes activation (Cd38, Cd69) genes expression. Immunohistochemistry for HER2 and nuclear p53 expression, CD8 and NK cells cytolytic activity (CD107a) of tumor infiltrating lymphocytes and for CD80 was performed. Non parametric statistics was used.

Results: In patients with EAC, HER2 overexpression, CD80 and CD86 expression and CD8 + lymphocyte infiltration and activation were not different than in those who without it. HER2 overexpression correlated inversely with the presence of necrosis within the tumor (tau=-0.18, p = 0.46). In patients with EAC nuclear p53 overexpression, CD69 mRNA expression within the tumor was lower than in those without it (p = 0.038 and p = 0.014, respectively). On the contrary, CD80 and CD86 expression and CD8 + lymphocyte infiltration were not different in the two groups.

Conclusion: In EAC, HER2 overexpression does not seem to affect immune surveillance mechanisms based on CD80-CD28 signaling and CD8 lymphocyte activation. Its effect on invasiveness seemed to be more related on tumor cell immortalization. On the other hand, nuclear p53 overexpression within the tumor seem to inhibit lymphocyte activation suggesting a possible role in tumor immune modulation.

Disclosure of Interest: None declared

P1136 THE DEVELOPMENT OF A NOVEL ENDOSCOPIC ORTHOTOPIC TUMOUR MODEL FOR OESOPHAGEAL CANCER

V. Sehgal¹, M. A. Butt¹, L. Funnell¹, H. Pye¹, S. Khan¹, I. Puccio¹, A. Sultan¹, J. Woodhams¹, S. Mosse¹, B. Draper², S. P. Patrick³, T. Kalber³, R. Hamoudi¹, M. Rodriguez-Justo⁴, M. Pule², M. Lythgoe³, M. Novelli⁴, L. B. Lovat¹

¹Centre for Gastrointestinal Intervention, ²Research Department of Haematology, ³Centre for Advanced Biomedical Imaging, University College London, ⁴Department of Histopathology, University College Hospital London NHS Foundation Trust, London, United Kingdom

Contact E-mail Address: v.sehgal@ucl.ac.uk

Introduction: The incidence of oesophageal adenocarcinoma (OAC) continues to rise rapidly. A clinically relevant animal model of OAC is needed to help study the effectiveness of novel therapeutic strategies for OAC. Current animal models have many limitations. Models that involve the injection of cells into the flanks of rodents do not replicate the native environment of OAC. Surgical models producing permanent biliary reflux that can lead to cancer are limited by the need for highly skilled surgical techniques, difficult reproducibility and significant morbidity to the animals involved. We describe a novel orthotopic tumour model for OAC. Our model is based upon the injection of tumour cells into the rodent oesophagus under direct endoscopic visualisation.

Aims & Methods: Two human tumour cell lines were used – OAC (OE19) and colon adenocarcinoma (HT29). Both lines were stably transfected to express luciferase and maintained in 5% CO2 at 370 C. 6-8 week-old female nude athymic rats (RNU Rat) were used for all experiments. A high-resolution diagnostic endoscope was used to perform all endoscopic procedures. Animals were anaesthetised using Isoflurane with concomitant oxygen given. Under direct visualisation, OE19 or HT29 tumour cells were injected. Immediately after endoscopy, 1ml of D-Luciferin (20mg/ml) was injected i.p. to follow luciferase-expressing OE19/HT29 tumour implantation. After 15 minutes, rats were inserted into a whole body cooled charged-coupled device (CCD) camera Photon Imager system and images obtained. All animals had Bioluminescent imaging (BLI) and endoscopy performed regularly to look for evidence of tumour growth.

Results: Implanted tumour cells were detected immediately after injection using BLI. Weekly, non-invasive BLI and regular endoscopic observation detected successful orthotopic tumour growth. Histological tissue samples confirmed the presence of tumour ulcerating the overlying squamous mucosa and infiltrating into, and through, the muscularis propria. This mirrors closely the behaviour of a primary human OAC.

Conclusion: We have developed a novel, more clinically relevant, orthotopic tumour model for OAC. By utilising rodent gastroscopy, our model replicates the native environment in which OAC grows and provides an opportunity for us to better understand the natural history of OAC in a manner that confers considerably less morbidity to animals than current models allow.

Disclosure of Interest: None declared

P1137 HOW OFTEN IS UPPER GASTROINTESTINAL CANCER MISSED DURING ENDOSCOPY? DATA FROM A DISTRICT GENERAL HOSPITAL (DGH)

A. Vaziri¹, D. Morris¹

¹Gastroenterology, East and North Hertfordshire NHS Trust, Stevenage, United Kingdom

Contact E-mail Address: arashvaziri86@gmail.com

Introduction: Recent studies report between 6 to 14% of patients with a gastric and oesophageal cancer had an oesophagogastroduodenoscopy (OGD) up to three years prior to diagnosis that did not report malignancy. This has prompted a national effort to improve the quality of OGD. We have examined our records from a DGH which serves a population of 500,000 patients to assess how often cancers could be missed and whether there are any factors which are associated with this. We define a possible missed cancer as one where there was a previous endoscopy within the last 3 years.

Aims & Methods: Our aim is to achieve quality improvement to OGD via the analysis and modulation of contributing variables. We retrieved computerised records of 65 patients diagnosed with gastric and oesophageal cancer over a year from between April 2013 and April 2014. We investigated our endoscopy database for whether the patients had endoscopies within the last 3 years. We reviewed the previous endoscopies for a number of factors including the age of the patient, the grade of the endoscopist, the finding at prior endoscopy, the number of biopsies taken and the pathology report at any noted abnormal sites, the use of sedation for the patient, the comfort scores and the urgency of the procedure. We then compared the results of this analysis with a comparison group of all the patients who had been diagnosed as having oesophageal or gastric cancer at their first endoscopy.

Results: There were 48 oesophageal cancers and 17 gastric cancers. In 6 (9.2%) of these cases there had been an endoscopy within the preceding 3 years. The average age of patients in the missed cancer group and comparison group were 71 and 69.6 respectively.

A greater proportion of patients in the missed cancer group were sedated (100% vs 69%). A smaller proportion of patients in the missed cancer experienced moderate or severe discomfort (0% vs 13.6%). In the missed cancer group a greater proportion of patients were on the emergency endoscopic bleed list (33% vs 7%). In both the missed cancer and the comparison group the proportion of endoscopies performed by Consultant Gastroenterologist was approximately 67%.

An analysis of the missed cancer cases found that in all 6 cases an abnormality had been noted in the area where the cancer was subsequently found. 3 of these cases had Barrett’s oesophagus in all cases multiple biopsies were performed and interval repeat endoscopy was arranged. In one case the endoscopist described a benign oesophageal stricture and did not biopsy, repeat biopsy 8 month later demonstrated malignancy. In 2 cases inflammation was noted at the lower oesophagus and stomach; firstly in the form of a malignant 4cm GOJ polyp and secondly in the form a malignant gastric ulcer. In the oesophagitis case no biopsies were taken and in the gastritis case biopsies suspected Iron pill gastritis.

Conclusion: In a small but important number of patients we potentially miss cancer at OGD. In our analysis the performance of the OGD for acute haemorrhage and not taking a biopsy were associated with missing cancers. There did not seem to be a negative association with the use of sedation, the discomfort of the patient or seniority of endoscopists. We will be continuing to monitor our ‘missed cancer’ rate and promote quality OGD by emphasising the importance repeating endoscopies limited by bleeding and the sampling of abnormal sites.

Disclosure of Interest: None declared

P1138 COMPARISON OF THE CLINICOPATHOLOGICAL CHARACTERISTICS AND THE SURVIVAL OUTCOMES BETWEEN THE SIEWERT TYPE II/III ADENOCARCINOMAS

C. Leitão¹, P. Sousa², J. Castela³, I. Guerreiro³, S. M. Ferro³, S. Ferreira³, J. Freire⁴, A. Luis³, R. Casaca⁵, A. Bettencourt⁵, P. Chaves⁶, A. D. Pereira³

¹Serviço de Gastrenterologia, Hospital Amato Lusitano - Unidade Local de Saúde de Castelo Branco, Castelo Branco, ²Serviço de Gastrenterologia, Hospital Santa Maria, ³Serviço de Gastrenterologia, ⁴Serviço de Oncologia, ⁵Serviço de Cirurgia, ⁶Anatomia Patológica, Instituto Português de Oncologia de Lisboa, Lisboa, Portugal

Contact E-mail Address: catia.f.leitao@gmail.com

Introduction: In the recent decades, the incidence of adenocarcinomas of the esophagogastric junction (AEGJ) has significantly increased. There are some disagreements regarding its pathogenesis, classification and approach. According to the Siewert classification, there are 3 types of AEGJ, depending if the lesion’s epicenteris located 5cm above the esophagogastric junction (EGJ) (I), in the EGJ (II) or 5cm below it (III). The protocol of our institution establishes that AEGJ type I should be treated as esophageal cancer and the AEGJ II/III as gastric cancer, with similar treatment protocol.

Aims & Methods

Aim: To analyze the clinical characteristics and survival outcomes in AJEG II and AJG type III tumours.

Methods: Retrospective analysis of consecutive patients with EGJ II/III tumours referred from Mar/2009 to Jun/2014 followed by our institution's multidisciplinary team. Clinicopathological characteristics and survival were analyzed. Statistics: chi-square test (categorical data). Kaplan–Meier curves/log-rank test (survival outcome), and log-rank test (statistical significance).

Results: A total of 109 patients (EGJ II n=50; EGJ III n=59) were included , 75 men, with a mean age of 66 ± 13 years. Demographic features were comparable between the two groups.

Eighty five patients had intestinal type adenocarcinoma and 24 had poorly cohesive carcinoma. This last histologic pattern was more frequent in EGJ III tumors (p = 0.037). AEJG cancer staging: I (7/109), II (46/109), III (20/109) e IV (36/109). Eleven patients were submitted to surgery only, 26 underwent surgery plus perioperative chemotherapy, 16 completed neoadjuvant chemotherapy before the surgery and palliative treatment in 54 patients. There were no differences regarding staging and treatment between the two groups.

The degree of tumor regression induced by chemotherapy and evaluated in the surgical specimen was similar between the groups (p = 0.589). For EGJ II and EGJ III tumors, the 36 months overall survival rate was 28.9% versus 29.4 %, respectively (p = 0.733). In the subgroup of patients treated with curative intention, the 36 months overall survival rate was 46.7% versus 49.8 %, respectively (p = 0.90).

Conclusion: In our series, there were no differences in clinicopathological characteristics and survival outcomes in EGJ II and EGJ III tumors, except for histological pattern with poorly cohesive carcinoma being more frequently found in EGJ III tumors. We consider that despite a possible distinct pathogenesis, these tumors have similar clinical behavior.

Disclosure of Interest: None declared

P1139 EFFICACY AND TOXICITY OF SECOND-LINE CHEMOTHERAPY IN PATIENTS WITH ADVANCED OESOPHAGEAL SQUAMOUS CELL CARCINOMA PROGRESSING AFTER A FIRST LINE OF 5-FLUOROURACIL AND PLATINUM-BASED THERAPY: AN AGEO RETROSPECTIVE MULTICENTRIC STUDY

C. Auzolle¹, B. Landi², A. Pozet³, R. Coriat¹, M. Dhooge¹, M. Ducreux⁴, M. Mons⁴, B. Brieau¹, I. Baumgartner⁵, J. M. Gornet⁶, A. Lièvre⁷, J. Taieb², J.-B. Bachet⁸, C. Locher⁹, F. Mary¹⁰, F. Bonnetain³, O. Dubreuil¹¹

¹75014, Hôpital Cochin, ²75015, Hôpital Européen Georges-Pompidou, Paris, ³25030, Methodology and Quality of Life in Oncology Unit (EA 3181), Besançon University Hospital, Besançon, ⁴94800, Gustave Roussy, Villejuif, ⁵94010 , Hôpital Henri Mondor, Créteil, ⁶75010, Hôpital Saint Louis, Paris, ⁷92210 , Hôpital René Huguenin, Saint-Cloud, ⁸75014, Hôpital Pitié Salpêtrière, Paris, ⁹77100, CH Meaux, Meaux, ¹⁰93009, Hôpital Avicenne, Bobigny, ¹¹75013, Hôpital Pitié Salpêtrière , Paris, France

Contact E-mail Address: claire.auzolle@orange.fr

Introduction: 5-fluorouracil (5-FU) and platinum-based chemotherapy (CT) is considered as a standard of care in first line treatment of metastatic oesophageal squamous cell carcinoma (SCC). Few data, essentially with taxane regimens, are available on the efficacy and toxicity of a second-line treatment. We therefore conducted a study to assess the efficacy and toxicity of second-line CT in such patients after progression during first line CT with 5-FU plus platinum.

Aims & Methods: Between January 2003 and December 2013, every patient from eleven medical centers with a metastatic or unresectable locally advanced oesophageal SCC who received a second line therapy after progression while on 5-FU and platinum (Cisplatin or Oxaliplatin) CT were retrospectively included. We collected and compared the data on overall survival (OS), progression free survival (PFS) and toxicity, using the NCI classification, from the beginning of the second-line for all patients and specifically for patients treated with Taxane (Paclitaxel or Docetaxel) or Irinotecan-based regimens.

Results: 68 patients (OMS 0-1 : 87%) were included : 51 (75%) received a second line CT with a taxane-based (22) or irinotecan-based regimen (29), and 17 received another CT regimen. Among these 51 patients, the median OS was 7.9 months and median PFS were 4.9 months. The 22 patients treated with Taxane had an OS and PFS of 7.5 months and 3.9 months respectively. The patients treated with Irinotecan-based chemotherapy had an OS and PFS of 8.7 months and 5.4 months respectively. The difference was not statistically significant between the two groups of patients (p = 0.28). One year survival rates was 32% for all patients (41.3% for Irinotecan-based CT group and 14.4% for Taxane group). The rates of severe toxicity (grade 3-4) and discontinuation of treatment related to toxicity were similar in the two groups. No toxic death was observed.

Conclusion: In this study, patients treated with a second-line therapy after progression under 5-FU and platinum CT, achieved a median OS of 7.9 months. Irinotecan and taxane based regimens showed no major differences in terms of toxicity and efficacy. These two types of regimen could be used in patients with good performance status. Prospective studies are necessary to determine which treatment would be the most appropriate.

Disclosure of Interest: None declared

P1140 A COMPARATIVE STUDY COMPARING A NEW ANTI-REFLUX STENT TO A CONVENTIONAL OPEN STENT IN THE PALLIATION OF DISTAL OESOPHAGEAL CANCER

C. Kanagasundaram¹, J. Segal², A. Leahy¹

¹Gastroenterology, Watford General Hospital, London, ²Gastroenterology, Lister Hospital, Stevenage, United Kingdom

Contact E-mail Address: cynthia_kanagasundaram@hotmail.com

Introduction: Oesophageal cancer is the sixth most common cause of death from cancer in the United Kingdom and worldwide. It accounts for 7,701 deaths in the UK in 2012.¹ Oesophageal cancer has a poor prognosis with a 5 year survival rate of 10-15%.^2,3 Unfortunately, greater than 50% of patients have unresectable cancers at presentation and most of these will go onto develop progressive dysphagia.⁴

There are various therapies to palliate dysphagia, oesophageal stenting has now become the main treatment option of choice for palliative oesophageal malignancy. Oesophageal intubation with a self-expanding stent is the treatment of choice for stenosing tumours, where rapid relief of dysphagia in a one stage procedure is desirable.⁵ There have been various stent designs marketed that incorporate an anti-reflux valve stent with a view to reducing this complication. Currently the British Society of Gastroenterology concluded that anti-reflux stents confer no benefit above standard stents.⁵

Aims & Methods: To compare a new anti-reflux stent with a conventional open stent in the palliation of patients with distal oesophageal cancer. This is a prospective study involving 40 patients with cancer involving the gastro-oesophageal junction. All patients will have been deemed inoperable within the local multi-disciplinary team meeting. Patients will receive either an anti-reflux stent (cardia-valve stent, Premier endoscopy) or a conventional open stent (ultraflex, Boston Scientific). All stents will be partially covered and placed across the gastro-oesophageal junction.

Quality of life will be measured and analysed using the oesophageal module European Organisation into Research and Treatment of Cancer questionnaire (EORTC QLQ-OES18). The questionnaires will be recorded by the attending endoscopist/physician at weeks 0 and 1. Differences between groups will be statistically evaluated by the Mann-Whitney test.

Results: There were 15 Ultraflex stents and 8 Cardiovalve stents that were followed up. Baseline EORTC QLQ-OES18 showed no significant differences in baseline scores (the Z-Score is -0.7423, the p-value is 0.4593).

At week one follow up there was no significant differences in the EORTC QLQ-OES18 between the two groups. The Ultraflex group had a EORTC QLQ-OES18 increase score of 38 compared with a 0 increase in overall score in the Cardiovalve group (The Z-Score is -0.3151. The p-value is 0.74896).

Conclusion: There was no significant differences in EORTC QLQ-OES18 scores between the two groups at week one suggesting that the stents appeared have similar quality of life profiles at week one post insertion. This is a small study and longer time follow up data is currently ongoing with 3 month follow up data of 40 patients currently being analysed.

Disclosure of Interest: None declared

P1141 COMPARISON BETWEEN ARGON PLASMA COAGULATION AND SELF-EXPANDABLE METAL STENT PLACEMENT IN THE PALLIATIVE TREATMENT OF INOPERABLE OESOPHAGEAL CANCER

D. E. Sigounas¹, C. Krystalis¹, G. Couper², S. Paterson-Brown², J. N. Plevris¹

¹Centre for Liver & Digestive Disorders, ²University Department of Surgery, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom

Contact E-mail Address: J.Plevris@ed.ac.uk

Introduction: Self-expanding metal stents (SEMS) are the main palliative modality used in inoperable oesophageal cancer¹. Other palliative options, including Argon plasma coagulation (APC), have been used and found effective². Comparative studies between those modalities are scarce and the preference of SEMS as the palliation modality of choice is not based on solid evidence.

Aims & Methods: The aim of this study was to assess the relative efficacy of SEMS and APC in inoperable oesophageal cancer palliation, in terms of survival. This was a single centre, retrospective analysis of all patients (n=233) with inoperable oesophageal cancer not receiving chemo-radiotherapy, treated with SEMS (n=163) or APC (n=70) as primary palliation modalities, between January 2000 and July 2014. Patient characteristics were retrieved from hospital records and Charlson Comorbidity Score (CCS) was calculated. Kaplan-Meier curves were created for each treatment modality and survival intervals were compared by the log-rank test separately for stage III and IV disease. A further analysis was performed after excluding patients surviving less than a month in order to minimize any potential selection bias.

Results: Patients having APC as primary treatment were older (median: 80 Vs 76 years, p = 0.01) and had a higher CCS (median 1 Vs 0, p = 0.02) compared to SEMS, but still had a significantly better survival. Median survival for patients treated with APC and SEMS was 257 (Interquartile range-IQR: 137, 414) and 151 (IQR: 61, 241) days respectively in stage III disease while it was 135 (IQR: 43, 238) and 70 (IQR: 32, 148) days respectively in stage IV disease. Both differences were statistically significant (0.02 and 0.05 respectively). After excluding patients not surviving more than a month, median survival in stage III patients was 257 (IQR:137,414) days for APC, compared to 162 (IQR: 100,285) for SEMS and in stage IV disease, median survival was 166 (IQR: 111,243) days for APC compared to 97 (IQR: 59,164) for SEMS. The difference was statistically significant in stage III (p = 0.04), whereas it was not in stage IV (p = 0.07).

Conclusion: Thsi study provides evidence that using APC as the primary palliation modality may significantly improve survival compared to SEMS in inoperable oesophageal cancer when patients are not candidates for chemo-radiotherapy. Further prospective studies to confirm those findings are needed.

Disclosure of Interest: None declared

P1142 LEARNING CURVE FOR DETECTING SUPERFICIAL HEAD AND NECK CANCER DURING SURVEILLANCE USING NARROW BAND IMAGING ENDOSCOPY

H. Morimoto¹, T. Yano¹, M. Imajoh¹, K. Tomohiro¹, S. Oosera¹, Y. Oono¹, I. Ikematsu¹, K. Kaneko¹

¹Endoscopy Division, National Cancer Center Hospital East, Kashiwa, Japan, Chiba, Japan

Contact E-mail Address: hmorimot@east.ncc.go.jp

Introduction: Narrow-band Imaging (NBI) is effective in detecting superficial head and neck squamous cell carcinoma (HNSCC) in patients with esophageal squamous cell carcinoma (ESCC), and we introduced the surveillance for HN region using NBI for all patients with ESCC before treatment. However, skilled endoscopic technique is necessary to survey pharyngo-laryngeal region and detect the superficial cancer during upper GI endoscopy, and detection rate of superficial cancer by beginner endoscopists is unknown. The aim of our study was to compare the performance in detecting HNSCC between beginner endoscopist and expert, and investigate detection leaning curves in beginner.

Aims & Methods: ESCC patients who fulfilled the following criteria, and underwent surveillance for pharyngo-laryngeal region using per oral endoscopy with NBI between January 2011 and March 2015 were recruited from our database, (1) initially diagnosed ESCC; (2) initial endoscopic examination with NBI in our hospital; (3) no history of any HNSCC; (4) no synchronously HNSCC was detected in previous hospital. All patients provided written informed consent before examination.

We compared the detection rate of HNSCC during initial endoscopic examination between beginner (less than 1 years’ experience of surveillance) and expert (at least 3years’ experience), and between the first 3 months of beginner ’s first year (period A) and 3 to 12months (period B).

Results: 747 patients (median age 68) were enrolled, and total 36 endoscopists (26 beginners and 10 experts ) performed the surveillance endoscopic examination. A total of 63 HNSCCs were detected in 47 patients (6.3%) and all of the lesions were superficial cancer. The lesions were located in hypopharynx (n=39 ), oropharynx (n=19), and larynx (n= 5). HNSCC detection rate was 4.4% in beginner and 7.1% in expert, (p = 0.19). No beginner could detect superficial HNSCC in the first 3 months (period A), but detection rate was 5.9% during period B (p = 0.069). In period A, detection rate of beginners was significantly lower than that of expert (0% vs 7.1%, p = 0.040), however, there was no significantly deference between beginners and experts during period B (5.9% vs 7.1%, p = 0.73).

Conclusion: Detection of superficial HNSCC during endoscopic surveillance with NBI might be difficult for novice endoscopists. However, detection rate was improved and almost as same as an expert after 3 months of intensive endoscopic training.

Disclosure of Interest: None declared

P1143 CLINICAL OUTCOMES OF PERORAL ENDOSCOPIC MYOTOMY FOR ACHALASIA DEPEND ON MANOMETRIC SUBTYPE

J. Y. Cho¹, W. H. Kim¹, K. B. Hahm¹, K. H. Ko¹, S. P. Hong¹

¹Digestive Disease Center, CHA Bundang Medical Center, CHA University, Seongnam-si, Korea, Republic Of

Contact E-mail Address: cjy6695@dreamwiz.com

Introduction: Peroral endoscopic myotomy (POEM) is known to be safe and effective endoscopic surgery compared with surgical myotomy for achalasia patients. A higher percentage of patients with type II achalasia successfully treated with laparoscopic Heller myotomy than patients with types I and III achalasia.

Aims & Methods: We evaluated whether manometric subtype was associated with response to treatment in a patients treated with POEM. Esophageal pre-treatment manometry data were collected from 53 cases that was performed POEM from November 2011 to August 2014 at two tertiary referral centers. Manometric tracings were classified according to the 3 Chicago subtypes.

Results: Among 53 cases, 35 type 1, 8 type 2 and 10 type 3 achalasia were included. There was no difference in pre-POEM Eckardt score, basal LES pressure, and integrated relaxation pressure (IRP) between type 1, type 2 and type 3 group (6.1 ± 3.9 vs. 8.4 ± 3.6 vs. 6.6 ± 3.4; p = 0.215, 27.3 ± 29.8 vs. 39.7 ± 12.3vs. 34.1 ± 32.8mmHg; p = 0.089, and 23.4 ± 29.6 vs. 30.1 ± 14.9vs. 19.2 ± 28.8mm Hg; p = 0.709). All patients showed a significant improvement in Eckardt score after POEM during median follow-up of 16 months (6.1 ± 3.9vs. 0.6 ± 2.4; p < 0.001, 8.4 ± 3.6 vs. 0.6 ± 1.4; p = 0.008, 6.6 ± 3.4vs1.0 ± 2.0; p< 0.001). But there was difference in decreased degree of Eckardt score between type 1, type 2 and type 3 group (p = 0.637), LES pressure was significant decrease only for type 2 group (23.5 ± 16.3 vs.16.1 ± 12.4; p = 0.113, 39.7 ± 12.3 vs. 19.5 ± 4.4;p=0.029, 34.1 ± 32.8 vs. 16.8 ± 17.2; p = 0.421). IRP score was significant decrease only fortype 1 group (23.4 ± 18.3vs.11.0 ± 9.5;p=0.014, 30.1 ± 14.9vs. 12.50 ± 7.5; p = 0.057, 19.0 ± 29.0vs. 11.6 ± 12.3; p = 0.886).

Conclusion: POEM showed good clinical outcomes in any manometric subtype. In the future, large prospective study is needed to confirm that POEM can be considered as standard treatment in any subtype of achalasia patients.

Disclosure of Interest: None declared

P1144 METABOLIC TUMOUR WIDTH PREDICTS POSITIVE CRM IN OESOPHAGEAL CANCER

K. Foley¹, R. Hills², J. Wheat³, A. Christian⁴, P. Fielding⁵, W. G. Lewis³, A. Roberts¹

¹Radiology, University Hospital of Wales, ²Haematology Clinical Trials Unit, Cardiff University, ³Surgery, ⁴Pathology, ⁵Wales Research & Diagnostic PET Imaging Centre, University Hospital of Wales, Cardiff, United Kingdom

Contact E-mail Address: foleykg@cardiff.ac.uk

Introduction: Circumferential resection margin (CRM) involvement is universally regarded as a poor prognostic indicator in both oesophageal and rectal cancer surgery, but prediction of threatened CRM in the former is challenging. MRI accurately predicts CRM involvement in rectal cancer, but has proved technically difficult in oesophageal cancer.

Aims & Methods: The study aims to test the association between PET/CT defined tumour variables and CRM positivity. Prospectively collected data on 95 consecutive patients (median age 65 (range 24-82), 74 male, 85 adenocarcinoma, 9 SCC, 1 HGD) with FDG-avid oesophageal and junctional tumours, initially treated with surgical management +/- neo-adjuvant therapy were included. Five PET/CT defined variables; SUVmax, metabolic tumour length (MTL), metabolic tumour width (MTW), metabolic tumour volume (MTV) and total length of nodal disease (NLoD), were entered into a binary logistic regression model. Primary outcome was CRM positivity.

Results: Twenty-five patients had surgery alone, 65 received neo-adjuvant chemotherapy and 10 received neo-adjuvant chemo-radiotherapy. CRM was positive in 57.9%. A statistical trend was observed between MTW and CRM involvement in all patients (HR 0.68 (95% CI 0.44-1.04); p = 0.07). MTW was independently and significantly associated with CRM positivity in 60 patients treated with neo-adjuvant chemotherapy (HR 0.53, 95% CI 0.31-0.92, p = 0.02). There was a significant difference between the upper and lower quintiles in this group (mean MTW 0.97 vs 3.93cm, p < 0.001).

Conclusion: MTW of oesophageal tumours can predict CRM positivity. This knowledge further informs the MDT, suggesting neo-adjuvant chemo-radiotherapy should be given prior to surgery.

Disclosure of Interest: None declared

P1145 METFORMIN USE DURING TREATMENT OF RESECTABLE ESOPHAGEAL CANCER PATIENTS IS NOT ASSOCIATED WITH BETTER OUTCOMES

L. Spierings¹, H. van Laarhoven¹, S. Lagarde², M. van Oijen¹, S. Gisbertz², J. Wilmink¹, M. Hulshof³, S. Meijer⁴, M. Anderegg², M. van Berge Henegouwen²

¹Medical Oncology, ²Surgery, ³Radiotherapy, ⁴Pathology, Academic Medical Center, Amsterdam, Netherlands

Contact E-mail Address: h.vanlaarhoven@amc.nl

Introduction: Metformin use has been associated with a dose-dependent increased response to neo-adjuvant chemo(radio)therapy in esophageal cancer patients. However, no association between metformin use and overall survival (OS) has been reported yet. The aim of our study is to investigate the effect of metformin use on pathological response as well as OS and disease-free survival (DFS) in patients with resectable esophageal cancer.

Aims & Methods: Between March 1994 and September 2013 all patients undergoing an esophagectomy for esophageal and gastro-esophageal junction cancer after neo-adjuvant chemo(radio)therapy with curative intent were included in a prospective database. A complete pathological response was defined as ypT0N0M0, Mandard 1. Kaplan-Meier curves with log rank testing were performed for OS and DFS.

Results: Four hundred and sixty-one patients were included with a median follow-up of 24 months (range 1-228); 43 patients were diagnosed with diabetes mellitus type II (9.3%) of whom 31 patients used metformin (6.7%). A total of 95 (20.4%) patients had a complete pathological response, which did not differ between metformin users (19.4%) and non-metformin users (20.5%, p = 0.14). We observed neither a statistically significant difference between metformin users and non-metformin users for median OS (20.8 vs 24.4 months, p = 0.840), nor for median DFS (20.5 vs 20.3 months, p = 0.845). A subgroup analysis in patients with diabetes mellitus type II showed a non-significant increase in median OS for metformin users (43.6 months) compared to non-metformin users (21.4 months, p = 0.237). For median DFS a similar non-significant increase was observed for metformin users (36.1 months) compared to non-metformin users (20.2 months, p = 0.163).

Conclusion: The use of metformin did neither result in in higher pathological response rates nor in an improved OS or DFS compared to non-metformin use in patients receiving neo-adjuvant chemo(radio)therapy for resectable esophageal cancer. In contrast to what has been postulated for other tumor types, metformin may not have a beneficial effect in esophageal cancer.

Disclosure of Interest: None declared

P1146 CLINICAL COMORBIDITIES FOR ESOPHAGEAL CANCER IN THE LAST THREE DECADES IN ITALIAN PATIENTS

F. Cavallin¹, M. Scarpa¹, R. Alfieri¹, M. Cagol¹, E. Ancona¹, C. Castoro¹

¹Oncological Surgery Unit, Veneto Institute of Oncology (IOV-IRCCS), Padova, Italy

Contact E-mail Address: marcoscarpa73@yahoo.it

Introduction: The incidence of esophageal cancer (EC) has been increasing worldwide during the last few decades. The aim of this study was to investigate the variation in clinical comorbidities in a large cohort of Italian EC patients in the same period.

Aims & Methods: A retrospective cohort study was performed using a prospectively collected database. All patients presenting with a diagnosis of primary EC at the Center for Esophageal Diseases located in Padua between January 1, 1980, and December 31, 2011, were included in the study. Data on local comorbidities (reflux disease, Barrett esophagus, previous caustic ingestion, achalasia, peptic disease), previous regional neoplasms, radio-induced tumors, previous distant neoplasm and systemic comorbidities. Joinpoint regression analysis was performed to estimate annual percentage changes (APCs).

Results: A total of 4440 patients were included in the present study. Reflux rate increased until 1997 (APC 7.57%, p < 0.01) and then leveled (APC -3.18%, p = 0.10). The rate of patients presenting with Barrett esophagus increased from 1.4% in the first period to 6.3% in the last period (APC 6.95%, p < 0.01). Gastric ulcer rate started decreasing since 2004 (APC -18.93%). The rate of previous local neoplasm increased until 1995 (APC 8.47%) and then leveled (APC -3.11%). The rate of radio-induced tumors varied from 0% in the first period to 7.1% in the last period, without significant trend (APC 5.37%,). Few patients (less than 1% overall) had achalasia or previous caustic ingestion. The rate of patients presenting with a previous distant neoplasm increased from 3.0% in the first period to 7.8% in the last period (APC 2.97%, p < 0.01). Advanced liver disease and pulmonary disease decreased over time (APCs -2.94% and -1.94% , respectively; both p < 0.01), whereas hypertension, diabetes and cardiac disease increased (APCs 6.56% , 2.11% and 2.56%, respectively; p < 0.01).

Conclusion: In the last three decades patients with EC showed significant and clinically meaningful changes in their local and systemic comorbidities. These chages should be taken into account when dealing with such patients.

Disclosure of Interest: None declared

P1147 ENDOSCOPY VS. SURGERY FOR HIGH-RISK EARLY ESOPHAGEAL CANCER

M. Kollar¹, J. Krajciova², J. Maluskova¹, E. Honsova¹, A. Pazdro³, T. Harustiak³, Z. Vackova², J. Spicak², J. Martinek²

¹Clinical and Transplant Pathology Department, ²Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, ³Third Department of Surgery, 1st Faculty of Medicine, Charles University in Prague and Motol University Hospital , Prague, Czech Republic

Contact E-mail Address: marek.kollar1@seznam.cz

Introduction: Endoscopic treatment is a standard therapeutic option for patients with early esophageal cancer (EAC) with mucosal invasion (T1a). For patients with “high-risk“ T1a cancer (e.g. advanced grading (G3/G4), invasion to lymphatic (L+) or blood vessels (A+), high degree of tumor cells dissociation (TCD 3) and for patients with T1b cancer (with any sm invasion)), surgery still remains a standard therapeutic approach.

Aims & Methods: To compare outcomes of endoscopic vs. surgical treatment in patients with high-risk EAC. High-risk cancer was defined as any cancer with submucosal (sm) invasion or mucosal cancer with at least one of the following: G3/G4 differentiation, invasion to blood (A+) and/or lymphatic (L+) vessels and high tumor cells dissociation (TCD3).

A single-center study. Patients with EAC underwent endoscopic resection (ER) or endoscopic submucosal dissection (ESD). Patients with high-risk EAC were referred for surgery if there were no contraindication such as advanced age, multiple co-morbidities, patient's refusal, etc. All other patients continued (if necessary) with endoscopic treatment which consisted of further sessions of ER (or ESD) and/or radiofrequency ablation (RFA). After treatment, all patients have been followed up for a median of 22 months (range 48-119).

Results: A total of 57 patients (50 men, 7 women, median age 63) underwent endoscopic treatment for EAC (47x adenocarcinoma, 9x squamous carcinoma, 1x duplicity (EAC + SCC)). Twenty-three patients (40%) had low-risk T1a cancer, and endoscopic treatment was considered curative. The remaining 34 patients (60%) had high-risk EAC (sm invasion: 56%; T1a cancers with “high-risk“ features: 44%).

Eleven “high-risk“ patients (32%) were referred for esophagectomy and 23 patients (68%) continued with endoscopic treatment. In one patient, the planned esophagectomy was finally not performed due to tumor generalization found during the operation. Among 10 patients who underwent esophagectomy, local residua of malignancy were present in only one (10%) patient and lymph node metastases have not been detected in any of these patients. During the follow-up, none of the patients who underwent esophagectomy has shown signs of generalization or a tumor relapse and no patient died.

In 23 “high risk” patients undergoing endoscopic treatment, local complete remission of neoplasia was achieved in all of them after a median of 2 treatment sessions. Neither local recurrence of neoplasia nor tumor generalisation have been observed so far, and there was no cancer related mortality.

Conclusion: Endoscopic therapy appears to be an effective alternative to esophagectomy in patients with “high-risk“ early esophageal cancer.

Disclosure of Interest: None declared

P1148 INSTRUMENTAL PERFORATION IN ESOPHAGEAL CANCER : NONOPERATIVE TREATMENT WITH SELF-EXPANDABLE COVERED METAL STENTS

M. Anselmi¹, A. M. Gemmato², M. Figueroa²

¹Surgery, University of Concepcion. Chile, ²Surgery, University of Concepcion, Concepcion, Chile

Contact E-mail Address: manselmi@udec.cl

Introduction: The standard approach to esophageal perforations consists of conservative treatment or surgery. Recent studies have suggested that stentgrafting may improve the treatment outcome of patiens with oesophageal perforation. However in neoplastic disease there still lack of evidence.

Aims & Methods: To assess the efficacy of endoscopic management of instrumental esophageal perforations in patients with neoplastic oesophagus using selfexpandable covered metal stents.

This is a prospective single-center study of 16 consecutive oesophageal cancer patients with acute therapeutic endoscopy perforation suffered during a dilatation of a neoplastic stenosis.

The mean age was 78 years, 8 patients (50%) were female, in 14 (87.5%) the tumor was located in the thoracic oesophagus and 2 ( 12.5%) in the cardioesophageal region. The histological type was squamous cell carcinoma in 14 (87.5%) and adenocarcinoma in the remaining 2 (12.5%). In 15 patients the diagnosis was made inmediately after the dilatacion by routine endoscopic and radiological post procedure review and in one case (6.3%), the perforation was diagnosed 22 hrs later. In the first 10 patients a fully covered self-expanding 18 mm in diameter metallic stent was inserted. In the remaining 6, in order to prevent migration, a 22 mm in diameter partially covered prosthesis was used.

The outcome of patients and immediate complications (up to 24 hrs post procedure), early (30 days) and late (over 30 days) were studied. Patients were monitored up to 90 after the perforation.

Results: The prosthesis insertion was successful in all patients. In 6 (37.6%) immediate morbidity associated with the perforation was found: 3 (18.8%) subcutaneous emphysema and 3 (18.8%) transient fever. The presence of early complications was found in 3 cases (18.8%), 2 of them developed a pleural effusion and a slight mediastinitis and one pleural fistula secondary to esophageal stent migration (18 mm completely covered). The prosthesis remained in place until the end of follow up in the remaining 15 patients (93.5%).

Oral intake was restarted by a mean of 3.6 ± 1.2 days ( range 1 – 7) and mean duration from the stent insertion to discharge was 8.3 ± 2.4 days ( range : 2 – 21). At the end of follow up, the 15 patients who survived had recovered the hability of oral feeding.

One patient died 19 days post procedure, as a result of pleural fistula secondary to a fully covered 18 mm esophageal stent migration, giving 30 day a mortality rate for this series of 6.3%.

Conclusion: The use of self-expanding metal stent for the treatment of esophageal instrumental perforations in patients with esophageal cancer is a safe and effective method, with low morbidity, adequate recovery of oral intake and short hospital stay.

Disclosure of Interest: None declared

P1149 RELATION BETWEEN THE LOCATION OF SUPERFICIAL BARRETT’S ESOPHAGEAL ADENOCARCINOMA (S-BEA) AND THE DIRECTION OF DUODENOGASTRIC REFLUX

M. Omae¹, J. Fujisaki¹, T. Shimizu¹

¹Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

Contact E-mail Address: masami.nego@jfcr.or.jp

Introduction: s-BEAs in Barrett’s esophagus are frequently found in the right wall of the esophagus.¹⁾ Why are they located on the right wall? Tongue-like SSBE was more frequent in the right anterior wall (in the 12 to 2 o’clock position) than at other locations (*P < 0.05).²⁾ Okita et al reported using pH monitoring with 8 channel sensors and patients with non-erosive reflux esophagitis (NERD) and reflux esophagitis had radial asymmetric acid exposure that was predominanton the right wall of the distal esophagus.³⁾

Aims & Methods: This study revealed the relation between the location of s-BEA and the direction of duodenogastric reflux.

33 s-BEA patients were enrolled in this study. 28 patients (28/77; 74.8%) had long segment Barrett’s esophagus (LSBE), the others (5/33; 15.2%) had SSBE. The invasion depth in 18 s-BEAs was mucosal cancer (18/33; 54.5%), the remaining was submucosal cancer (15/33; 45.5%). We performed 24-h pH monitoring study before s-BEA was treated by ESD or operation. All patients took PPI. This catheter has 8 pH sensors circumferentialy arrayed at the same level of the device (developed by Shimane Medical University and Star-medical). The catheter was inserted transnasally into the esophagus and positioned 2cm above the squamo-columnar junction (SCJ). All 33 s-BEA patients took the position for 24 hours every day as same as possible and they didn’t take special position by themselves. This device didn’t rotate in their every position. We measured the maximal total duration of acid (pH < 4.0) and alkaline (pH > 8.0) reflux in all 33 s-BEA patients. We evaluated the relation between the location of s-BEA and the direction of the maximal total duration of acid and alkaline reflux.

Results: Regarding as maximal total duration of acid reflux, in 28 SSBE patients except for 4 patients without acid reflux, the rate of coincidence was 19/24 (79.2%). On the other hand, in 5 LSBE patients, the rate of coincidence was 4/5 (80.0%). Regarding as maximal total duration of alkaline reflux, in 28 SSBE patients except for 3 patients without alkaline reflux, the rate of coincidence was 20/25 (80.0%). On the other hand, in 5 LSBE patients, the rate of coincidence was 3/5 (80.0%). In all 33 s-BEA patients, the rate of coincidence for maximal total acid or alkaline reflux was 29/33 (87.9%).

Conclusion: The location of the s-BEA mostly corresponds with the direction of maximal total duration of acid and alkaline reflux. Measuring the direction of duodenogastric reflux by using pH monitoring with 8-channnel might be useful for early detection of the s-BEA in LSBE.

Disclosure of Interest: None declared

P1150 ENDOSCOPIC DIAGNOSIS FOR THE EARLY PRIMARY MALIGNANT MELANOMA OF ESOPHAGUS (PMME)

T. Omori¹, R. Nakamura², H. Kawakubo², M. Tsutsui³, H. Sugiura⁴, K. Kameyama⁵, Y. K. Kitagawa²

¹Endoscopy Center, Kawasaki Municipal Ida Hospital, Kawasaki, ²Surgery, Keio university, Tokyo, ³Surgery, ⁴Pathology, Kawasaki Municipal Kawasaki Hospital, Kawasaki, ⁵Pathology, Keio university, Tokyo, Japan

Contact E-mail Address: t-omori@jcom.home.ne.jp

Introduction: Primary malignant melanoma of the esophagus (PMME) is a rare disease, and most of the PMME had been found in advanced stage. Treatment for PMME is basically esophagectomy, but treatment effect is poor and it’s prognosis is extremely poor. In contrast, the early esophageal squamous cell carcinoma and early gastric carcinoma can be cured by the local treatment such as the endoscopic resection (ER;ESD/EMR). The early diagnosis and treatment is the best strategy to improve the patients’ survival. Based on this fact, we supposed that the early PMME have low possibility of lymph nodes metastases, and we can get a good prognosis by the ER. Early detection is important in early treatment. But early PMME is more rarethan advanced PMME and is very difficult to find because we do not know collect endoscopic findings. To clarify the endoscopic findings of the early PMME will help to find early PMME.

Aims & Methods: The purpose of this study is to clarify the endoscopic findings of the early PMME. From Jan 2006 to Apr 2015, we experienced 4 cases of early PMME. For those 4 cases, we investigated their clinical and pathological and endoscopic findings.

Results: We have 2 female cases (57y.o and 71y.o) and 2 male cases (69y.o and 61y.o). There ware no symptoms in all cases, and all cases were found by screening endoscopy. Lesions were located in all part of esophagus. The lesion size was 3-40mm. In most of the lesions, the shape of lesion was flat type (0-IIb). Slight irregularities appeared when the cancer becomes thicker, and in 1 case, clear polypoid elevation can be seen. In benign melanosis, color of lesion is a thin black from pale gray, but in PMME the color of lesion was a very clear black and the lesion was composed of irregular large and small black-spots. The demarcation line was irregular, ill-defined and faded in color. Case1: A 57y.o female with 6 lesions. All lesions were 0-IIb. After the CT examination showing no metastasis, ER was performed, as the patient chose ER rather than operation. Pathological diagnosis was PMME, T1a-LPM,ly0,v0. We followed up every 6 months by endoscopy, and 8 times ER had been done for new lesions. 8.5 years has passed from the first ER, the patient is alive and free from disease. Case 2: A 69-year male with 2 lesions. All lesions were 0-IIb. After the informed consent, 2 lesions were removed by ER. The pathological diagnosis were PMME, T1a-LPM,ly0,v0. Case 3: A 71y.o female with 1 lesions. Type of lesion was 0-Ip + IIa + IIb, lesion size was 40mm and clear black polypoid elevation can be seen. Total esophagectomy with LN dissection was done. Pathological diagnosis was PMME, T1a-LPM,ly0,v0,n0. Case4: A 61-year male with 2 lesions. All lesions were 0-IIb. After the informed consent, 2 lesions were removed by ER. The pathological diagnosis was PMME, T1a-LPM,ly0,v0 in both lesions.

Conclusion: Next 4 Features are typical endoscopic findings of early PMME 1. Shape of lesion: flat(0-IIb)∼slight irregularities on surface 2. Color of lesion: very clear black 3. Structure of lesion: irregular large and small black-spots 4. Demarcation line: irregular, ill-defined and faded in color. Our cases indicate the possibility to cure early PMME by ER.

Disclosure of Interest: None declared

P1151 CLINICAL OUTCOME ACCORDING TO ENDOSCOPIC EVALUATION OF NEOADJUVANT CHEMOTHERAPY AND PATHOLOGICAL TUMOR REGRESSION GRADE IN RESECTABLE ESOPHAGEAL SQUAMOUS CELL CARCINOMA

T. Kadota¹, T. Yano¹, S. Fujii², K. Hatogai³, Y. Yoda¹, T. Kojima³, H. Daiko⁴, K. Kaneko¹

¹Department of Gastroenterology, Endoscopy Division, ²Department of Pathology Division, Research Center for Innovative Oncology, ³Department of Gastroenterology, Oncology Division, ⁴Department of Esophageal Surgery, National Cancer Center Hospital East, Kashiwa, Japan

Contact E-mail Address: tkadota@east.ncc.go.jp

Introduction: Neoadjuvant chemotherapy (NAC) followed by surgery is one of the standard treatments for patients with resectable esophageal squamous cell carcinoma (ESCC). It was reported that surgery following NAC improved survival compared with surgery alone, especially in patients whose surgically resected specimens were assessed as pathological regression with chemotherapy. However, the clinical impact utilizing endoscopy for evaluating efficacy after NAC, especially for prediction of recurrence, is unknown.

Aims & Methods: The aim of this study was to clarify the correlation between recurrence-free survival (RFS) and the NAC therapeutic efficacy for primary tumors. The NAC therapeutic efficacy was evaluated with endoscopic evaluation and pathological tumor regression grade (TRG) of the superficial layer of the surgically resected tumor. We enrolled patients with clinical T2/3 ESCC who underwent NAC followed by definitive surgical resection in our institution between January 2008 and March 2013. We excluded any case that an endoscopic examination had not been performed after NAC. The NAC therapeutic effect was retrospectively estimated with each endoscopic image by 3 independent endoscopists, and patients were classified into 4 groups according to the degree of tumor regression (marked reduction [MR]: 90% or more reduction; half reduction [HR]: 50% or more reduction; insufficient reduction [IR]: less than 50% reduction; ineffective, resulting in growth [IG]: progression). In addition, we evaluated the therapeutic effect on the mucosal layer of resected specimens as grade 0–3 on the basis of TRG of the primary tumor. We evaluated RFS and clinicopathological factors, including endoscopic classification of the NAC therapeutic efficacy and superficial TRG. This study was approved by an institutional review board in our institution.

Results: We evaluated 129 patients (110 men, 19 women; median age 65 years, range 36-77) who were eligible. The numbers of patients with clinical stage IB/IIA/IIB/IIIA/IIIB/IIIC/IV were 9/28/6/50/25/2/9, respectively. The numbers of patients in group MR/HR/IR/IG were 44/35/44/6. In group MR, only 9 patients were regarded as complete remission. The numbers of patients with grade 0/1a/1b/2/3 superficial TRG score were 45/32/20/17/15. Most patients with grade 2-3 were evaluated as MR, and most patients with grade 0-1a were evaluated as IR or IG. The median follow-up period was 24 months, 56 patients had recurrence or death, and the median 3-year RFS was 56.3%. The median 3-year RFS of patients in group MR/HR/IR/IG was 85.3%/48.0%/39.3%/16.7%, respectively. A multivariate analysis demonstrated that cN factors and endoscopic classification for the NAC therapeutic efficacy were independent preoperative predictors of RFS, and ypT, ypN, ypR factors and superficial TRG were independent postoperative predictive factors.

Conclusion: In this study, there was a relationship between tumor recurrence and both of endoscopic evaluation for the NAC therapeutic efficacy and superficial TRG. These two factors could identify risk of recurrence.

Disclosure of Interest: None declared

P1152 OUTCOME OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR SUPERFICIAL PHARYNGEAL SQUAMOUS CELL CARCINOMA

T. Oyama¹, A. Takahashi¹

¹Endoscopy, Saku Central Hospital Advanced Care Center, Saku, Japan

Introduction: Recently, the detection of superficial pharyngeal squamous cell carcinoma has been increasing in Japan. However, the outcome and prognosis for endoscopic submucosal dissection (ESD) are unknown.

Aims & Methods: The aim of this study is to clarify the outcome and prognosis of pharyngeal Squamous cell carcinoma (SCC) treated by ESD.

86 pharyngeal SCC in 65 patients were treated by ESD from Jan. 2006 to Jul. Dec. 2014 in Saku Central Hospital. All ESD were performed using a Hook knife under general anesthesia with tracheal intubation. Clip with line or forceps was used to make traction during ESD.

Male/Female was 64/1. Median age was 67 (40-92) years old. Median tumor size was 5 (1 - 50) mm. Median observation duration was 71(1-127) months.

Results: 1) En bloc and R0 resection rate was 100% (86/86) and 93% (80/86), respectively. R0 resection was defined as En block resection, lateral and vertical margin was negative.

2) Complication: Perforation wasn’t shown. Delayed bleeding rate was 1% (1/86). Dysphasia was shown in 2% (2/86).

3) Invasion depth: Epithelial (EP) and subepithelial (SEP) lesion was 69% (59/86) and 31% (27/86) respectively.

96% (51/53) of small lesions less than 10mm were EP. On the other hand, 76% (25/33) of large lesions 10mm or bigger were SEP.

4) Lymph-duct involvement

0/59 of EP and 4/27 of SEP had lymph duct involvement.

5) Local recurrence

One case had local recurrence. The case was SEP with lymph duct involvement. The local recurrent lesion was treated by re-ESD.

6) lymph-node metastasis (LNM)

LNM rate of EP and SEP was 0% and 11% (3/27), respectively. Two of three patients had lymph duct involvement. All of 3 patients were treated by lymph node dissection.

7) Prognosis

Two patient died of pharyngeal SCC. Both patients had SEP with lymph duct involvement, and refused additional treatment such as chemo-radio therapy.

Conclusion: ESD is a useful treatment method for superficial pharyngeal SCC. Additional therapy should be recommended for the patient who had lymph duct involvement.

Disclosure of Interest: None declared

P1153 LONG-TERM OUTCOMES OF ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) FOR EARLY ESOPHAGEAL SQUAMOUS CELL CARCINOMA (EESCC): A LARGE STUDY OF 344 CONSECUTIVE CASES

Y.-S. Zhong¹, I. Take²

¹Zhongshan Hospital of Fudan University, ²Endoscopy Center, Shang hai, China

Introduction: To evaluate the long-term outcomes of Endoscopic submucosal dissection (ESD) for early esophageal squamous cell carcinoma (EESCC) on a large patient cohort in China.

Aims & Methods: From January 2007 to November 2013, a total of 344 EESCC patients with high-grade dysplasia (HGD) and superficial squamous cell carcinoma of esophagus were included in the present retrospective study and all of the patients were treated by ESD. Demographic, pathological, clinical parameters and follow-up data were collected and analyzed.

Results: In this study, the mean age of patients was 61.8 ± 8.2 years. The ratio of male and female patients was 250:94. Among these patients, there were 78 HGD and 226 superficial squamous cell 72 epithelial or lamina propria (EP/LPM), 109 muscularis mucosa (MM) and 45 submucosal (SM1) cancer carcinoma. The median follow-up period was 34 months.

1) The complication rate was 30.5% (102/334), including 1 perforation, 1 pneumonia, 8 delayed bleeding and 92 (26.7%) postoperative stricture (defined as complaints of dysphagia). Balloon dilation under endoscopy were performed for 34 (9.9%) severe stricture patients who were suffering from aphagia.

2) Recurrence rate was 16.0%. The median time to recurrence were 18 (range 1-67) months. Longitudinal length>=3cm (p = 0.003), Circumferential range > 3/4 (p = 0.001), lymph vascular involvement (p = 0.004), postoperative stricture (p = 0.02), and combined with other cancer (p = 0.030) were independent predictors of recurrence. The 5-year progression-free survival for high risk group and low risk group are 35% and 80%, respectively.

3) The 5-year progression-free survival rate was 72%, for HGD, EP/LPM, MM and SM1 were 82.5%, 67.1%, 74.6%, and 54.2%, respectively (p = 0.003). The median progression-free survival time was 72 months. Metastasis were observed in 10 (2.91%) patients, which were 7 lymph node, 3 lung, 2 laryngeal, 2 liver, and 1 stomach metastasis.

4) The 5-year overall survival rate was 95%, for HGD, EP/LPM, MM and SM1 were 97.40%, 87.30%, 92.62%, and 78.60%, respectively (p = 0.008). The median survival time was 84 months. There were 14 (4.1%) patients died. Death due to esophageal cancer occurred in 6 patients (1.74%), and 5 patients died owing to other cancer. The circumferential range > 3/4 (p = 0.000), combined with other cancer (p = 0.000), and infiltration depth of lesion (p = 0.010) were independent predictors of overall survivals.

Conclusion: ESD is efficient to treat EESCC. The risk of recurrence after ESD were mainly associated with longitudinal length>=3cm, lymph vascular involvement, circumferential lesion >3/4, combining with other cancer, and postoperative stricture. Overall survival appears to be affected by circumferential lesion >3/4, combining with other cancer, and infiltration depth of lesion. These risk should be taken into account when considering the indications for ESD.

Disclosure of Interest: None declared

P1155 RELATION BETWEEN THE PROGNOSTIC NUTRITIONAL INDEX AND MORBI-MORTALITY POST R0 RESECTION IN THE GASTRIC CANCER

A. Borda¹, J. J. Vila¹, I. Fernández-Urién¹, J. Jiménez-Pérez¹, J. M. Zozaya¹, A. Guerra¹

¹Gastroenterology, Complejo Hospitalario De Navarra, Pamplona, Spain

Contact E-mail Address: abordamartin@yahoo.es

Introduction: A low prognostic nutritional index (PNI) has been related to a high complication rate after gastric cancer resection in Japanese reports, with no data in western countries.

Aims & Methods: To analyse in our media the relation between a pathologic PNI and the frequency and severity of post surgery gastric cancer complications.

This retrospective study included 124 cases of gastric carcinomas, consecutively operated in our centre, with R0 resection. The PNI was calculated with the form: [10 x serum albumin (g/dl) + 0.005 x total lymphocytes count/mm²], being pathological a PNI < 40. Complication rates were compared between the group with normal and pathological PNI (Chi² test). A multivariate analysis of the complication rates according to PNI was performed [Cox model, stepwise, hazard ratio (HR) and 95% confidence interval (CI)] adjusting for: age >68 years, preoperative ASA (ASA 1-2 vs ASA 3-4) and pTNM stage (I, II and III + IV). We determined the relation between PNI ≥ 40 and < 40 and the severity of the complications according to Martin and cols. classification (J Am Coll Surg. 2002; 194: 565-77), grouped in: no complications, mild, severe and exitus.

Results: Complication rate was: no complication: 95 (76.6%), mild complications: 14 (11.3%), severe: 12 (9.7%) and exitus: 3 (2.4%). 11.5% of cases presented a PNI < 40. Patients with pathological PNI registered a high frequency of complications: 24.1% vs 7.5% [p 0.021; OR = 3.91; CI95% = (1.09-14.17)], which was confirmed in the multivariate analysis [p 0.042; HR = 3.61; CI95% = (1.05-12.43)]. Furthermore, we registered complications with a higher severity in the group with pathological PNI: mild = 14.3% versus 11.1%; severe = 21.4% versus 8.3% and exitus = 14.3% versus 0.9% (p = 0.005).

Conclusion: 1. Patients with a pathological Prognostic nutritional Index (<40) show a three times higher risk of suffering complications after R0 resection in the gastric cancer. 2. This higher risk is independent of age, preoperative ASA and pTNM tumor stage. 3. Besides, cases with a PNI < 40 were associated with a significant higher rate of severe complications and postoperative exitus.

Disclosure of Interest: None declared

P1157 CLINICOPATHOLOGIC FEATURES OF SYNCHRONOUS MULTIPLE EARLY GASTRIC CANCERS

J. H. Kim¹, E. J. Kim¹, K. O. Kim¹, J.-W. Chung¹, Y. J. Kim¹, K. A. Kwon¹, W. K. Lee², D. K. Park¹

¹Department of Internal Medicine, ²Department of Surgery, Gachon University Gil Medical Center, Incheon, Korea, Republic Of

Contact E-mail Address: junghokimm@gilhospital.com

Introduction: The multifocality rate of early gastric cancer (EGC) ranges from 4 to 21%, but there are few data regarding both lymph node metastasis and characteristics of synchronous multiple gastric cancers of patients with EGC.

Aims & Methods: We investigated the characteristics of synchronous multiple gastric cancers of patients with EGC after endoscopic or surgical treatment. We retrospectively reviewed the clinicopathological features from patients who were diagnosed with EGC after endoscopic resection or surgical treatment between February 2008 and May 2013. Of 999 EGC patients treated with endoscopic or surgical resection, 987 were included in the analysis.

Results: Of 987 patients, 578 (58.6%) were initially treated with surgical resection and 37 (9.5%) were diagnosed with synchronous multifocal EGC. The mean age at treatment of patients with solitary and synchronous multifocal EGC was 61.5 ± 11.7 and 64.3 ± 9.6 years, respectively (p > 0.05). The rates of lymph node metastasis were 4.6% (44/950) in solitary EGC and 5.4% (2/37) synchronous multifocal EGC (p > 0.05). In the multivariate analysis, synchronous multifocal EGC was associated with male and depth of invasion in main lesion compared solitary EGC (p < 0.05). In the subgroup analysis, 70.3% and 64.9% of patients with multiple synchronous EGC were found to have tumors located in same thirds and same aspect of the stomach, respectively.

Conclusion: Synchronous multifocal EGC does not increase the risk of lymph node metastasis compared with solitary EGC, and tumor location is an important determinant of occurrence in synchronous lesion. Clinician should pay special attention to detect synchronous lesion near the main tumor.

Disclosure of Interest: None declared

P1158 ENDOSCOPIC CLUE OF EN BLOC RESECTION IN GASTRIC INDEFINITE NEOPLASIA

R. Dae Gon¹, O. Sook Kyoung¹, K. Dae Hwan¹, K. Hyung Wook¹, C. Cheol Woong¹, P. Su Bum¹, K. Su Jin¹

¹Pusan National University, Yangsan Hospital, Yangsan, Korea, Republic Of

Contact E-mail Address: gon22gon@naver.com

Introduction: When gastric indefinite neoplasia (category 2 lesion) from endoscopic forceps biopsy is diagnosed, it is difficult to decide management. Especially, in some situations such as suspicious of early gastric cancer (EGC) macroscopically, it is hard to decide. The aim of this study was to discuss the results of final results of gastric indefinite neoplasia and associated clinical factors predictive of early gastric cancer.

Aims & Methods: This retrospective study enrolled 142 patients of gastric indefinite neoplasia on index forceps biopsy. We analyzed the initial endoscopic features of lesions and predictive factors of early gastric cancer (EGC).

Results:

Variable	Univariate analysis		Multivariate analysis
P value	OR	P value	OR	95% CI
Lesion size ≥ 10mm
Nodular	0.003	12.500	0.021	11.401	1.432-90.759
Redness color	0.002	4.941	0.066	2.998	0.928-9.686
Pale color	0.007	4.048	0.014	3.777	1.306-10.923

After complete work-up, the final pathologic diagnoses were early gastric cancer (n = 34, 23.9 %), adenoma (n = 16, 11.3%), and non-neoplasm (n = 92, 64.8%). In the univariate analysis, lesion size more than 10 mm, surface nodularity and erythema were associated risk factors. In the multivariate analysis, lesions diameter (p =0.019, OR 12.501, 95% CI 1.537-91.269) and surface redness (p = 0.015, OR 3.598, 95% CI 1.414-12.314) were significant risk factors.

Conclusion: Gastric indefinite neoplasia with larger size (≥ 10mm) and erythema might be need more definite diagnostic modalities rather than simple follow up endoscopy.

Disclosure of Interest: None declared

P1159 THE EFFICACY OF COLONOSCOPY IN PATIENTS WITH ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY GASTRIC CANCER

J. Joon Ho¹, K. Dae Hwan¹, K. Hyung Wook¹, C. Cheol Woong¹, P. Su Bum¹, K. Su Jin¹

¹Department of Internal Medicine, Pusan National University, Yangsan Hospital, Yangsan, Korea, Republic Of

Contact E-mail Address: gon22gon@naver.com

Introduction: Our goal is to study the risk of colorectal cancer in patients who underwent endoscopic submucosal dissection(ESD) with EGC as compared to controls. And We assessed the need for surveillance colonoscopy in patients with early gastric cancer.

Aims & Methods: The study group included a total of 180 patients with EGC that underwent ESD. As a control group, 430 sex and age-matched patients without gastric neoplasm were included. All of the patients underwent screening colonoscopy before or after 6months from gastric ESD between January 2010 and December 2013.

Results: High-risk colorectal neoplasm was diagnosed in 52/170 patients (30.5%) in EGC group and 12/420(2.8%) in controls (p < 0.01). Colorectal cancer was diagnosed in 22/170 patients (12.9%) in EGC group and 3/220 (1.3%) in controls (p < 0.01). Univariate analysis demonstrated that high-risk colorectal neoplasm was associated with presence of EGC, age, DM, and colorectal cancer was associated with presence of EGC, colorectal cancer family history. Multivariate analysis demonstrated that age (OR 6.19, 95% CI 3.5-11.5), EGC (OR 7.50, 95% CI 4.41-18.10) were risk factors for high-risk colorectal neoplasm. And the presence of age (OR 3.58, 95% CI 1.57-10.92), EGC (OR 6.47, 95% CI 2.87-15.10), colorectal cancer family history (OR 3.07, 95% CI 1.92-9.34) were risk factors for colorectal cancer.

Conclusion: The incidence of colorectal cancer who underwent an ESD for EGC group was higher than the control group. Therefore, we believe that screening colonoscopy should be considered in patients with ESD because of early gastric cancer.

Disclosure of Interest: None declared

P1160 RISK FACTORS OF SUBMUCOSAL OR LYMPHOVASCULAR INVASION IN THE TREATMENT OF ENDOSCOPIC SUBMUCOSAL DISSECTION OF EARLY GASTRIC CANCER

J. Dong Il¹, K. Dae Hwan¹, K. Hyung Wook¹, C. Cheol Woong¹, P. Su Bum¹, K. Su Jin¹

¹Department of Internal Medicine, Pusan National University, Yangsan Hospital, Yangsan, Korea, Republic Of

Contact E-mail Address: gon22gon@naver.com

Introduction: Lymph node metastasis is important to evaluate the indication of the submucosal dissection (ESD). Submucosal invasion and lymphovascular invasion is considered to be an independent risk factor for lymph node metastasis in early gastric cancer. Accurate diagnosis of the invasion depth in the previous ESD remains a challenge and can only be confirmed by final pathologic report following ESD. The purpose of the study is to identify risk factors for SM/LV invasion in early gastric cancer.

Aims & Methods: We studied retrospectively pathological data of patients treated ESD from Jan 2010 to May 2014 and presenting EGC of differentiated-type adenocarcinoma, 2.0 cm or smaller in size and no ulceration.

Results: Among 390 lesions consecutively resected by ESD, 297 lesions in 277 patients were included in this study. Submucosal and lymphovascular invasions were detected in 32 lesions. Multivariate analysis revealed two independent risk factors for SM/LV invasions: Histology of moderate-differentiated (odds ratio (OR) 4.082; 95% CI 1.925-8.616; P=0.008), location of upper and middle third (U/M) of stomach (OR 2.917, 95% CI 1.410-6.048;P=0.008).

Conclusion: Histology of moderate-differentiated adenocarcinoma, and location of U/M were identified as independent risk factors of SM/LV invasion in EGC meeting absolute criteria for ESD.

Disclosure of Interest: None declared

P1161 CLINICOPATHOLOGICAL FEATURES OF ALPHA-FETOPROTEIN -PRODUCING GASTRIC CANCER WITH ENTEROBLASTIC DIFFERENTIATION

K. Matsumoto¹, H. Ueyama¹, K. Matsumoto¹, Y. Akazawa¹, H. Komori¹, T. Takeda¹, T. Murakami¹, M. Hojo¹, A. Nagahara², T. Yao³, S. Watanabe¹

¹Gastroenterology, Juntendo Univ., Bunkyo-ku, ²Gastroenterology, Juntendo Univ. Shizuoka Hospital, Nagaoka, ³Pathology, Juntendo Univ., Bunkyo-ku, Japan

Contact E-mail Address: khmatsu@juntendo.ac.jp

Introduction: Gastric cancer with enteroblastic differentiation (GCED), which is a histologic type of alpha-fetoprotein (AFP)-producing gastric cancer, is very rare and its clinicopathological features have not been well investigated. Additionally, there is no report that focused on an early stage of GCED.

Aims & Methods: This study aimed to clarify the clinicopathological features of early stage of GCED by comparisons with conventional early gastric cancer (CGC: well to moderately differentiated carcinoma). We analysed 191 cases (143 males, 48 females; mean age 72.8 y; 214 lesions) of early gastric cancer that underwent endoscopic resection from September 2011 to February 2015 in our hospital. Five of 191 cases were GCED (2.6%). We evaluated the comparison between 5 cases (4 males, 1 female; mean age 75.8 y; 5 lesions) of early gastric cancer with a GCED component and 186 cases (139 males, 47 females; mean age 73.7 y; 209 lesions) of conventional early gastric cancer, clinicopathologically.

Results: No significant difference was observed in tumour locations (U/M/L = 1/2/2 and 23/91/95 in GCED and CGC, respectively), mean of tumour size (15.0 and 15.2 mm in GCED and CGC, respectively) and macroscopic types (flat or depressed type/ elevated type = 4/1 and 92/117 in GCED and CGC, respectively). Endoscopically, we could not find specific findings for GCED, and we did not anticipate deep submucosal invasion. No lesion was diagnosed as GCED by examination of biopsy specimens. Regarding depth of tumour invasion, total submucosal invasion rates were significantly higher in GCEDs than CGCs (60.0% vs. 11.4%, P<0.001). Furthermore, positive rates of lymphatic and venous invasion were significantly higher in GCEDs than CGCs (40.0 vs. 2.3%; and 60.0 vs. 0.4%, P<0.001). In 2 of 5 GCED cases, additional surgery was performed (A: T1N0M0, stage IA; B: T1N1M0, stage IIA). Histological examination demonstrated the presence of tubulopapillary carcinoma with clear cytoplasm at the deeper part of the mucosa. In all cases of GCED, the superficial mucosal layer was covered with a conventional tubular adenocarcinoma. Immunohistochemically, positive findings were as follows: AFP: 1/5(20%), PAS: 3/5(60%), glypican 3: 3/5(60%), SALL 4: 2/5(40%).

Conclusion: To our knowledge, this is the first report on multiple cases of early stage of GCED. Since GCED exists only in the deeper part of the mucosa in early stage cancer, preoperative diagnosis by biopsy is thought to be difficult. Additionally, ratio of lymphovascular invasion in GCED was significantly higher than CGC, which indicates that GCED has high malignant potential. Further investigations are needed to establish optimal treatment approaches for GCED.

Disclosure of Interest: None declared

P1162 DIFFERENCES IN MIRNA EXPRESSION PROFILES BETWEEN GIST AND LEIOMYOMA IN HUMAN SAMPLES ACQUIRED BY SUBMUCOSAL TUNNELING BIOPSY

K. Fujita¹, H. Kobara¹, H. Mori¹, S. Fujihara¹, T. Chiyo¹, T. Matsunaga¹, N. Nishiyama¹, M. Ayaki¹, T. Yachida¹, A. Morishita¹, M. Fujiwara², K. Okano², Y. Suzuki², H. Iwama³, T. Masaki¹

¹Gastroenterology and Neurology, ²Gastroenterological Surgery, Kagawa University Faculty of Medicine, ³Life Science Research Center, Kagawa University , Kita Kagawa, Japan

Contact E-mail Address: 92m7v9@med.kagawa-u.ac.jp

Introduction: A gastrointestinal stromal tumor (GIST) with malignant potential typically requires surgery. Differentiating GISTs from other submucosal tumors (SMTs), especially leiomyoma, is therefore important in daily practice. Although GISTs express specific proteins, such as c-kit and CD34, serum biomarkers for GISTs have not yet been established.

Aims & Methods: The aim of this study was to identify candidate microRNAs (miRNAs) for serum biomarkers of GIST through the investigation of miRNA expression patterns in human cases of GIST and leiomyoma. MiRNA expression was examined in 9 GIST samples and 6 leiomyoma samples that were diagnosed histopathologically and acquired by a novel sampling method, submucosal tunneling biopsy (STB). STB offers the advantage of sufficient tumor specimen acquisition without contamination under direct vision. Total RNA was extracted from these tissues and analyzed for miRNA expression patterns by microarray. Subsequently, reverse transcription and real-time qPCR were used to confirm specific miRNA overexpression in the microarray analysis, comparing GISTs with leiomyomas.

Results: Microarray analysis revealed the upregulation of 10 miRNAs and the downregulation of 22 miRNAs in GISTs compared to leiomyomas; in particular, the miR-140 families and miR-181a-5p were upregulated, whereas the miR-378 family was downregulated. MiRNAs extracted from tumor tissues clustered differentially between GISTs and leiomyomas. Real-time qPCR revealed that the expression level of miR-140-5p in GISTs was 28.5 times higher than that in leiomyomas, and the expression level of miR-140-3p was also 23.2 times higher in GISTs compared to leiomyomas.

Conclusion: The STB method provided suitable SMT samples for miRNA analysis. As shown by real-time qPCR, miR-140 family members may serve as serum biomarkers of GIST compared to leiomyoma, which could lead to the development of a non-invasive diagnostic tool.

Disclosure of Interest: None declared

P1163 PREDICTIVE FACTORS FOR METACHRONOUS GASTRIC CANCER AFTER HP ERADICATION IN THE POST-ESD (ENDOSCOPIC SUBMUCOSAL DISSECTION) STATUS

K. Moribata¹, M. Iguchi¹, H. Deguchi¹, Y. Maeda¹, N. Shingaki¹, T. Niwa¹, I. Inoue¹, T. Maekita¹, H. Tamai¹, J. Kato¹, M. Ichinose¹

¹Second Department of Internal Medicine, Wakayama Medical University, Wakayama city, Japan

Contact E-mail Address: moribata@wakayama-med.ac.jp

Introduction: Endoscopic submucosal dissection(ESD) is the standard therapy for early gastric cancer. Several studies reported successful Helicobacter pylori(HP) eradication reduced metachronous gastric cancer after ESD. In contrast, some other studies showed the HP eradication was not effective for reducing gastric cancer.

Aims & Methods: The aim of this study is to reveal the predictive factors for metachronous recurrence of gastric cancer after HP eradication in the post-ESD status.

370 patients with early gasric cancer received first ESD at our hospital between October 2004 and December 2012. Exclusion criteria were histories of gastric surgery, gastrectomy, and eradication, serologically HP negative, rejection of eradication, unsuccessful eradication, no recept of endoscopy after eradication. Of the 98 patients in the final analysis, we retrospectively evaluated endoscopic features associated with histopathological findings related to HP infection in the pre-ESD and post-eradication. A endoscopic examination in the post-eradication was carried out one year or more after eradication treatment. Outcome measures were the following endoscopic findings: fundic gland polyp, regular arrangement of collecting venules (RAC), flat erosion, severity of atrophy, intestinal metaplasia, rugal hyperplasia, nodularity, mucosal edema, spotty redness, xanthoma, and Map-like redness. These findings were analyzed to identify the predictive factor for recurrence.

Results: The subjects comprised 73 males and 25 females with a mean age (SD) of 68.0 (±8.9) years. There was no significant difference in age, gender, endoscopic findings except for map-like redness. Map-like redness after HP eradication was the only predictive factor showing a significant difference by univariate analyses. The cumulative recurrence-free survival was significantly lower in patients with map-like redness after HP eradication than in those without the finding since the time of successful HP eradication (p = 0.003, Log-rank test ).

Conclusion: Map-like redness after HP eradication is a vital factor for metachronous gastric cancer after HP eradication in the post-ESD status.

Disclosure of Interest: None declared

P1164 ENDOSCOPIC TREATMENT OF MALIGNANT GASTRIC OR DUODENAL OBSTRUCTION USING SELF-EXPANDABLE METAL STENT PLACEMENT

H. Lim¹, K. Jung², J. Y. Ahn², H.-Y. Jung², D. H. Kim², J. H. Lee², K. W. Jung², K. D. Choi², H. J. Song², G. H. Lee², J.-H. Kim²

¹Department of Internal Medicine, University of Hallym College of Medicine, Hallym University Sacred Heart Hospital, Anyang, ²Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea, Republic Of

Contact E-mail Address: forjkw@gmail.com

Introduction: Gastric outlet obstruction (GOO) is a clinical syndrome characterized by epigastric abdominal pain and postprandial vomiting due to mechanical obstruction. In past, treatment of malignant gastric outlet obstruction was palliative surgery including bypass through a gastro-jejunostomy. There have been significant technical advances in stent development and endoscopic technology over recent years. Self-expandable metal stents (SEMS) can be used to palliate patients with malignant gastric or duodenal obstruction and to restore the ability of oral feeding with the recent advances in endoscopic technology.

Aims & Methods: In this study, we tried to assess the feasibility and efficacy of SEMS which were inserted through the scope method for the palliation of malignant obstruction of gastric or duodenal obstruction. During January 2011 to April 2014, 220 patients with gastric or duodenal obstruction due to malignancy underwent endoscopic SEMS insertion at Asan Medical Center. We analyzed technical/clinical outcomes and complications according to the type of stent and the location of obstruction.

Results: Among 220 patients (median age was 63 years, men were 125), full covered SEMS was inserted in 16 patients, partial covered SEMS in 77 patients, and uncovered SEMS in 120 patients. %). The median width of stent was 20 mm (IQR, 20-20mm) and the median length of stent was 80 mm (IQR, 60-100mm). The location of obstruction was shown in gastric outlet including duodenal bulb (n=106), in duodenal 2nd and 3rd portion (n=114). Technical success was found in 213 of 220 cases (96.8%) and clinical success was in 184 of 213 (86.4%). According to the type of stent and site of obstruction, clinical success was shown in like these; full covered SEMS (15/16, 93.8%), partial covered SEMS (68/77, 88.3%), and uncovered SEMS (101/120, 84.2%) (p = 0.476); gastric outlet obstruction (95/104, 91.3%) and duodenal obstruction (89/109, 81.7%) (p = 0.039). Of total, migration was happened in 20 cases (9.1%) and obstruction was in 51 cases (23.2%). According to type and site, migration was shown in like these; full covered SEMS (6/16, 37.5%), partial covered SEMS (7/77, 9.1%), and uncovered SEMS (7/120, 5.8%) (p < 0.001); gastric outlet obstruction (16/104, 15.4%) and duodenal obstruction (4/109, 1.2%) (p = 0.003). According to type and site, obstruction was shown in like these; full covered SEMS (2/16, 12.5%), partial covered SEMS (17/77, 22.1%), and uncovered SEMS (32/120, 26.7%) (p = 0.409); gastric outlet obstruction (26/104, 25.0%) and duodenal obstruction (25/109, 22.9%) (p = 0.724). Early complications were observed in 10 patients and late complications were observed in 64 patients. The obstruction complication was occurred mainly (45 cases) in late complication patients. The median stent patency period was 84 days (IQR, 34.5-165.5 days) and median survival was 124 days (IQR 55.5-224.0 days).

Conclusion: In malignant GOO, We should carefully decide what type of stent to use according to the obstruction site. Especially, migration risk should be considered when fully covered stent is inserted at the peri-pyloric area.

Disclosure of Interest: None declared

P1165 EPSTEIN-BARR VIRUS ASSOCIATED GASTRIC CARCINOMA IN SOLID-ORGAN TRANSPLANT RECIPIENTS

K. Jung¹, H.-Y. Jung¹, H. K. Na¹, J. Y. Ahn¹, D. H. Kim¹, K. W. Jung¹, J. H. Lee¹, K. D. Choi¹, H. J. Song¹, G. H. Lee¹, J.-H. Kim¹

¹Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea, Republic Of

Contact E-mail Address: forjkw@gmail.com

Introduction: Epstein-Barr virus (EBV), as well as Helicobacter pylori, has been accepted as an infective agent causing gastric cancer (GC). In conventional gastric adenocarcinoma of the diffuse and intestinal types, EBV is found in 7%>14% of cases. Moreover, EBV associated GC (EBVaGC) occur more frequently in male and in young age group, in the proximal stomach. However, the incidence of EBV associated GC (EBVaGC) in patients that received solid organ transplantation (SOT) and immunosuppression therapy is still unknown.

Aims & Methods: The aims of this study were to evaluate the pathological characteristics and clinical outcomes of EBVaGC in patients who had performed SOT. Between January 1994 and December 2011, total 29 gastric carcinomas on 28 consecutive were confirmed and treated with endoscopic resection or operation in patients undergone SOT at Asan Medical Center, Seoul, Korea. Formalin-fixed paraffin-embedded tissue from these resection specimens were re-assessed for EBV by in situ hybridization and data from medical record were also reviewed retrospectively.

Results: Of the 6,491 patients who underwent SOT during the study periods, 30 patients (0.46%) with 31 lesions were diagnosed with gastric cancer. Among them, 28 patients with 29 lesions were treated by endoscopic resection or operation. The median age of patients was 59 years (IQR, 54-64 years) and men were 23. The median duration between transplantation and diagnosis of GC was 45 months (IQR, 34.5-80.5 months). Of total 29 GCs, 8 were found as EBVaGCs (27.5%) (6/23 males and 2/6 females). The location of tumor, histologic differentiation, initial stage[l1] and organ of transplantation showed no differences between EBVaGC and GC. The Helicobacter pylori was infected in 12.5% of EBVaGC and 23.8% in GC (p = 0.615).[l2] The survival rate was 62.5% (5/8) in EBVaGC and 81.0% (17/21) in GC (p = 0.299).

Conclusion: Although the incidence of EBVaGC was higher in SOT recipients than well-known incidence of EBVaGC in non-transplant patients, the pathological characteristics and clinical outcomes were not different according to the infection of EBV.

Disclosure of Interest: None declared

P1166 CLINICAL OUTCOMES OF ENDOSCOPIC RESECTION OF GASTRIC GASTROINTESTINAL STROMAL TUMOR

K. Jung¹, D. H. Kim¹, E. J. Gong¹, J. Y. Ahn¹, H. K. Na¹, J. H. Lee¹, K. W. Jung¹, K. D. Choi¹, H. J. Song¹, G. H. Lee¹, H.-Y. Jung¹, J.-H. Kim¹

¹Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea, Republic Of

Contact E-mail Address: forjkw@gmail.com

Introduction: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Up to date, total surgical resection still constitutes the only standard treatment for non-metastatic GISTs and a wide surgical margin is not necessary for total resection as long as the premise of negative margins is respected in comparison with that of other GI malignant tumors. With the recent advances in endoscopic technology, endoscopic resection (ER) has been attempted for the curative treatment of gastric GIST.

Aims & Methods: Here we aim to investigate the feasibility and safety of ER of gastric GIST. Subjects who underwent ER for gastric GIST at the Asan Medical Center from May 2005 to April 2014 were eligible. Patient factors, tumor factors, procedure factors, and clinical outcomes were evaluated using medical record.

Results: A total of 25 patients underwent ER for GIST. The median age was 58 years (42-72 years), and the male to female ratio was 1.5:1. The location of tumors were upper third of the stomach in 11 patients (44%), middle third in 5(20%), and lower third in 9(36%). The median size of tumors was 24.1 mm (range: 10-40 mm). The median procedure time was 37.5 minutes (range:10-80minutes). All lesions were divided into three groups according to the size and mitotic index; very low risk (16/25, 64%), low risk (7/25, 28%, and intermediate risk (2/25, 8%). Complications occurred in 5 patients (20%) including microperforation (n=4, 16%) and delayed bleeding (n=1, 5%). Five patients underwent sequential wedge resection of stomach because of microperforation and noncurative resection, and the pathologic evaluation revealed residual tumors in 2 patients. There was no recurrence or metastasis occurred during the median follow-up period of 49.9 months(range: 2-108 months).

Conclusion: ER of gastric GIST may be a feasible and safe method, on the basis of favorable clinical outcomes.

Disclosure of Interest: None declared

P1168 CLINICOPATHOLOGICAL REVIEW OF PIT DYSPLASIA AFTER ENDOSCOPIC RESECTION OF GASTRIC EPITHELIAL NEOPLASMS : THE FEATURES AND IMPORTANCE OF PIT DYSPLASIA

K. L. Hwang¹, D. H. Baek¹, G. A. Song¹, B. G. Song¹

¹Internal Medicine, Gastroenterology, Pusan National University Hospital, Busan, Korea, Republic Of

Contact E-mail Address: dhbeak@hanmail.net

Introduction: Endoscopic resection (ER) is widely accepted as appropriate treatment modalities for gastric epithelial neoplasms. However, issues regarding discrepancy between forceps biopsy and ER specimens or negative pathologic diagnosis (NPD) after ER have been rising. Recently pit dysplasia (PD) is suggested as one of subtypes of gastric dysplasia.

Aims & Methods: We aimed to review clinicopathologic features of cases with NPD after ER for early gastric neoplasms, and to evaluate the role of PD in these cases. From January 2006 to September 2013, 29 NPD lesions after ER, which had 1) available pretreatment forceps biopsy specimen, 2) correct targeting during ER, 3) no cautery artifact on resection specimen, were included in this study. Pretreatment forceps biopsy and ER slides were reviewed by 2 expert pathologists in gastrointestinal pathology.

Results: Review of 29 NPD lesions after ER showed PD in 16 lesions and no neoplastic pathology in 13 lesions. Initial pretreatment forceps biopsy diagnoses of 29 NPD lesions were low-grade dysplasia (LGD) in 17 lesions, high-grade dysplasia (HGD) in 7 lesions, and adenocarcinoma in 5 lesions. Reviewed diagnoses of initial pretreatment forceps biopsy were PD in 19 lesions, LGD in 4 lesions, adenocarcinoma in 2 lesions and no neoplastic pathology in 4 lesions. Taken together, of 29 NPD lesions after ER, 9 lesions (31%) were removed by forceps biopsy due to small size of the lesion, 4 NPL lesions (14%) were initially misinterpretated as neoplastic lesions, and 16 PD lesions (55%) were misinterpretated as NPD lesions in ER slides.

Conclusion: In about half of lesions initially interpreted as NPD after ER, they were diagnosed as LGD or HGD on initial biopsy specimen, and their final diagnoses were changed into PD. Therefore, the use of PD as a subtype of gastric dysplasia could narrow diagnostic discrepancy between initial forceps biopsy and ER and could lessen the frequency of NPD.

Disclosure of Interest: None declared

P1169 CLINICAL FACTORS ASSOCIATED WITH DUODENAL TUMOR: DIFFERENCE BETWEEN THE 2ND PORTION AND THE BULB

M. Ueda¹, J. Matsuzaki¹, H. Suzuki¹, T. Masaoka², S. Fukuhara¹, S. Miyoshi¹, H. Mori¹, Y. Iwao², Y. Sugino², T. Kanai¹

¹Internal medicine, Keio University School of medicine, ²Center for Preventive Medicine, Keio University Hospital, Tokyo, Japan

Introduction: Primary duodenal adenocarcinoma is a rare malignant neoplasm among all gastrointestinal malignancies which poor prognosis is likely to be associated with delayed diagnosis. Lee et al reported the characteristics and prognosis of 53 cases with duodenal adenocarcinoma [1]. According to this report, 14 of 60 cancers (23%) found in the 2nd portion and 8 of 12 cancers (67%) in the bulb were unresectable at diagnosis. This suggests that the duodenal tumors in the bulb would be rare but show poorer prognosis than those in the 2nd portion. The present case-control study was designed to evaluate the characteristics of patients with duodenal adenoma or adenocarcinoma. In addition, the characteristics between the tumor in the bulb and the 2nd portion were compared.

Aims & Methods: Patients who made a histological diagnosis of duodenal adenoma or duodenal adenocarcinoma at Keio University Hospital between January 2010 and June 2014 were enrolled as cases. On the other hand, two age- and gender- matched control subjects for each case were randomly extracted from individuals who underwent esophagogastroduodenoscopy for medical checkup in the same period and did not have duodenal tumors. Individuals with familial adenomatous polyposis or the Peutz-Jeghers syndrome were also excluded. Lifestyle characteristics, comorbidities, and endoscopic findings were compared between cases and controls.

Results: 157 cases (123 with duodenal adenoma and 34 with duodenal adenocarcinoma) and 314 age- and gender- matched healthy controls were investigated. Multivariable logistic regression analysis revealed that current smoking (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.3 - 4.6]), the presence of Barrett's esophagus (OR, 4.7; 95% CI, 2.5 - 8.8), the presence of fundic gland polyps (OR, 2.5; 95% CI, 1.5 - 4.4) and a history of malignant diseases (OR, 3.0; 95% CI, 1.8 - 5.2) were independently associated with the presence of duodenal tumor. The presence of duodenal tumor in the 2nd portion (n=137) was associated with current smoking (9% vs. 17%; p = 0.03), Barrett's esophagus (7% vs. 20%; p < 0.01), reflux esophagitis (7% vs. 13%; p = 0.045), fundic gland polyps (15% vs. 29%; p = 0.002) and a history of malignant diseases (13% vs. 24%; p = 0.006). On the other hand, the presence of duodenal tumor in the bulb (n=20) was associated with the presence of Barrett's esophagus (3% vs. 25%; p = 0.01) and a history of malignant diseases (10% vs. 40%; p = 0.01). The presence of open-type atrophy was inversely correlated with the presence of duodenal tumor in the 2nd portion (25% vs. 15%; p = 0.02), whereas the presence of open-type atrophy was more frequently observed in individuals with duodenal tumor in the bulb (28% vs. 40%; p = 0.38).

Conclusion: Clinical characteristics were different between individuals with the duodenal tumors in the 2nd portion and those in the bulb. These results suggest the differences of the etiology of tumor development between the locations of primary duodenal tumor.

Disclosure of Interest: None declared

P1170 CLINICAL OUTCOME OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY GASTRIC CANCER BEYOND THE EXPANDED CRITERIA

N. Shibukawa¹, N. Tatsumi¹, A. Kaneko¹

¹Gastroenterology, NTT West Osaka Hospital, Osaka, Japan

Contact E-mail Address: n_shibukawa@yahoo.co.jp

Introduction: Endoscopic submucosal dissection (ESD) has been widely undertaken for the treatment of early gastric cancer. However, the long-term outcome of ESD beyond the expanded criteria remains uncertain.

Aims & Methods: From July 2006 to February 2015, ESD for early gastric cancer was performed in 302 patients in our hospital, and 53 patients met beyond the expanded criteria. We retrospectively studied their clinical course after ESD.

Results: En bloc resection rate and complete resection rate were 90.6 % and 60.4 %, respectively. Both rates of postoperative bleeding and perforation after ESD were 3.8 %. Among the 53 patients beyond the expanded criteria, 16 (30.2 %) underwent additional gastrectomy (surgical group) and 37 (69.8 %) did not (non-surgical group). Local recurrence rate was 0 % in the surgical group and 2.7 % in the non-surgical group. Lymph node metastasis was observed in 18.8 % and 0 %, respectively. Distant metastasis was not observed in both groups. Three-year overall survival rate was 93.8 % and 78.4 %, respectively. Death due to gastric cancer was observed only one patient in the non-surgical group.

Conclusion: Beyond the expanded criteria does not always lead to cancer recurrence or metastasis. Thus, if additional gastrectomy cannot be underwent because of patient’s underlying condition or refusal, a close follow-up might be considered.

Disclosure of Interest: None declared

P1171 DETERMINANTS OF PATIENT'S AND DOCTOR'S DELAY IN DIAGNOSIS OF GASTRIC CANCER IN THE NETHERLANDS; A ROUTINE CARE DATA ANALYSIS

N. F. Van Erp¹, Y. Arik¹, C. W. Helsper¹, N. J. de Wit¹

¹Julius Center for Health Sciences and Primary Care, UMC Utrecht, Utrecht, Netherlands

Contact E-mail Address: nfvanerp@gmail.com

Introduction: An efficient diagnostic process is important to reduce burden of disease for gastric cancer patients. Duration of this diagnostic process and determinants of relatively long duration are unknown for the Netherlands.

Aims & Methods: The aim of the present study was to determine the duration of the different phases of the diagnostic process of gastric cancer patients in the Netherlands and to identify determinants of relatively long duration (‘delay’). A retrospective observational study was performed, using routine care data of 51 eligible gastric cancer patients diagnosed between 2008 and 2013, whose anonymized patient files were retracted from the Primary Care Network Utrecht (PCNU) database. Three phases in the diagnostic process were defined (T1 to T3): T1 – from onset of symptom(s) to first gastric cancer related consultation with general practitioner (GP); T2 – from first GP consultation to referral for diagnosis; T3 – from referral to final diagnosis. Based on manual exploration of free-text and coded data, the duration of these phases was determined. Median duration and interquartile ranges (IQR) were calculated in days. ‘Delay’ was defined as the longest quartile of phase duration. To find determinants of 'delay', the association between patient-, disease- and consultation related variables and 'delay' was assessed using univariate χ² and multivariate logistic regression analyses.

Results: The median time from onset of symptoms to final diagnosis was 128 days (IQR 61 - 213). Median duration of the different time periods was: T1: 17 days (IQR 3 - 42); T2: 22 days (IQR 4 - 66); T3: 34 days (IQR 15 - 56). The only variable for which a suspicion of an association with 'delay' was found was psychiatric co-morbidity in T2 (OR 2.27, 95%CI 0.93 - 5.57).

Conclusion: Dutch gastric cancer patients face a modest ‘delay’ in the diagnostic process in primary and secondary care. No clear determinants of long duration could be identified. The variation in duration of each phase, particularly in time from first consultation to referral by the GP, is substantial. Since the time from referral by the GP to final diagnosis was relatively long, increasing efficiency of the secondary care diagnostic process is likely to be the most effective intervention to reduce ‘delay’.

Disclosure of Interest: None declared

P1172 DEVELOPMENT OF AN E-LEARNING SYSTEM FOR THE ENDOSCOPIC DIAGNOSIS OF EARLY GASTRIC CANCER: AN INTERNATIONAL MULTICENTER RANDOMIZED CONTROLLED TRIAL

N. Uedo¹, K. Yao², M. Muto³, H. Ishikawa⁴, on behalf of Global e-Endo Study Team

¹Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, ²Endoscopy, Fukuoka University Chikushi Hospital, Chikushino, ³Therapeutic Oncology, Kyoto University Graduate School of Medicine, ⁴Graduate School of Medical Science, Kyoto Prefectural University, Kyoto, Japan

Contact E-mail Address: uedou-no@mc.pref.osaka.jp

Introduction: Gastric cancer ranks the third highest cause of cancer deaths worldwide. Except Japan and Korea where screening program is implemented, most of the gastric cancers were diagnosed at advanced stage. We suspect one of the reason why gastric cancers around the world were detected late is because of limited knowledge and experience of endoscopists. Accordingly, the authors have developed an Internet-based e-learning system to teach medical practitioners how to detect early gastric cancer using standard white light endoscopy.

Aims & Methods: The aim of this study was to evaluate effectiveness of the e-learning system on teaching good practice for endoscopic screening of gastric cancer. The study was designed as a randomized controlled trial. Medical practitioners around the world participated in this study with a signed consent form. The participants first undertook a pre-test via Internet, and then they were randomly allocated into two groups (e-learning and non-e-learning groups). Pre-adjustment strata were the pre-test score, experience of endoscopy, a nurse endoscopist or a medical doctor, and medical institution and country. The participants only in the e-learning group were allowed to access to the e-learning system that consisted of video lectures to learn basic knowledge and self-exercise tests to accumulate experience. A post-test was conducted in the both groups two months after the pre-test. The pre-determined primary endpoint was the difference in improvement rate of the test result (post-test score/pre-test score) between the two groups. After completion of the post-test, the e-learning system was opened for all participants.

Results: Five-hundred fifteen medical practitioners from 35 countries were assessed eligibility for this study. Finally, 322 participants who met inclusion criteria completed the pre-test and enrolled in this study. One-hundred sixty-six were allocated to the e-learning group and 166 were allocated to the non-e-learning. Among them, 151 participants in the e-learning group and 144 in the non-e-learning group had completed the post-test, and were included into the analysis. The mean improvement rates (standard deviation) of the test result in the e-learning and the non-e-learning groups were 1.24 (0.26) vs. 1.00 (0.16), respectively (P < 0.001). Namely, our e-learning system yielded substantial improvement to medical practitioners in the e-learning group, while there was no improvement for those in the non-e-learning group.

Conclusion: This global study demonstrated efficacy of our e-learning system to improve ability for endoscopic detection of early gastric cancer among medical practitioners worldwide. The effectiveness will be evaluated on improvement of early gastric cancer detection rate of all participants in actual clinical practice. (UMIN: R000012039)

Acknowledgements: HJ, Cardona, EC Castro-Filho, R Pittayanon, C Olano, F Yao, A Parra-Blanco, SH Ho, GA Alvarado, A Piscoya, ED Fedorov, AP Bialek, AA Mitrakov, LE Caro, C Gonen, S Dolwani, AB Farca, LF Cuaresma, JJ Bonilla, W Kasetsermwiriya, K Ragunath, SE Kim, M Marini, H Li, DG Cimmino, MM Piskorz, F Iacopini, JBY So, K Yamazaki, GH Kim, TL Ang, DM Milhomem-Cardoso, CA Waldbaum, WA Piedra-Carvajal, CM Hayward, R Singh, R Banerjee, GK Anagnostopoulos, Y Takahashi

Disclosure of Interest: None declared

P1173 ESD FOR GASTRIC TUMORS IN THE WESTERN WORLD: CHALLENGES TO FIT INTO STANDARD, EXPANDED INDICATIONS AND BEYOND

P. Kisoka¹, C. Loly², A. Mourin³, R. Yeung⁴, H. Piessevaux⁵, E. Danse⁶, T. Moreels¹, P. H. Deprez¹

¹Hepato-Gastroenterology, Clin univ St-Luc, Brussels, ²Hepato-Gastroenterology, CHU Sart-Tilman, Liege, ³Pathology, Clin univ St-Luc, Brussels, ⁴Hepato-Gastroenterology, Hopital de Jolimont, La Louviere, ⁵Clin univ St-Luc, Brussels, Belgium, ⁶Radiology, Clin univ St-Luc, Brussels, Belgium

Contact E-mail Address: pdeprez@uclouvain.be

Introduction: Compared to Asian countries, ESD is rarely performed for gastric lesions in the West. The aim of our study was to report our experience and results in absolute and expanded indications for endoscopic resection of early gastric cancer (EGC).

Aims & Methods: All patient files, included in a prospective register, treated for gastric lesions by endoscopic submucosal dissection between January 2005 and December 2014 were analysed focusing on pre-ER histology, curative resection rates, and clinical outcomes based on pathology specimen and follow-up. Patients were classified following the Japanese guidelines as standard (SC) and expanded criteria (EC). All patients not fulfilling these criteria were considered as “out of criteria” (OOC).

Results: The data for 118 consecutive gastric lesions resected by ESD in 106 patients were reviewed (mean follow-up 50 months), mean age 69 years, 71 (67%) men. Lesions were 70 EGCs, 23 HGD, 9 LGD adenomas, 4 neuroendocrine tumors, 10 benign various lesions. Mean lesion size was 25 mm (5-60). Perforation were observed in 2 pts (endoscopic management). R0 resection rate in EGC were 93% in SC (14/15 pts), 89% in EC (17/19 pts), and 42% (15/36 pts) in OOC. Significantly better resection rates were observed during the second period of ESD experience (2011-2014 vs 2005-2010: 100 vs. 86%, 90 vs 87% and 61% vs 22%, respectively. OOC classification was usually due to a combination of factors including lymphatic permeation (4), undifferentiated cancer foci (19), ulceration (12), and sm1 or 2 invasion (24). 13 pts with R1 resections and OOC underwent gastrectomy: 50% had no residual disease, all three intramucosal EGCs were staged pN0 whereas 2/10 of the ten EGCs reaching the submucosa were staged pN+ (20%).

Conclusion: In the Western world, a significant proportion of EGC treated by ESD are either expanded criteria indications or even out of criteria due to G3 foci, lymphatic permeation or a combination of factors. Most of these factors could not be detected before endoscopic resection. Excellent curative resection rates of more than 90% could be offered to patients with expanded indications. More than 2/3 of patients with R1 resection and OOC specimens were also effectively cured by ESD, as proven by subsequent gastrectomy. This treatment could therefore still be considered as a curative option in frail patients.

Disclosure of Interest: None declared

P1174 GERMLINE CDH1 MUTATIONS FOUND IN A SERIES OF SPORADIC GASTRIC CANCER PATIENTS

R. Cannizzaro¹, E. Orzes¹, L. Caggiari², M. De Zorzi², A. Buonadonna³, A. De Paoli⁴, P. Spessotto⁵, S. Maiero¹, M. Fornasarig¹, V. De Re²

¹SOC Gastroenterology, ²Bioproteomic Core Facility/BIT, ³Medical Oncology, ⁴Oncological Radiotherapy, ⁵Experimental Oncology, Centro Riferimento Oncologico, Aviano, Italy

Contact E-mail Address: rcannizzaro@cro.it

Introduction: Loss of cadherin 1 (CDH1) expression, which is normally involved in cell adhesion and maintenance of tissue architecture, is a hallmark of Hereditary Diffuse Gastric Cancer (HDGC).

The frequency of CDH1 germline mutations in families with HDGC is 25-30% but the real frequency and characterization of germline variants for CDH1 in sporadic Gastric Cancer (GC) patients is not known. Moreover, recently CDH1 mutations have been demonstrated to have a prognostic role in overall GC. It is important to determine the prevalence of germline CDH1 mutations in overall patients with GC.

Aims & Methods: To this end, we tested CDH1 for germline mutations in a population of patients with non-Hereditary GC.

Peripheral blood from 142 patients with a histopathological confirmed GC diagnosis was investigated for CDH1 mutations. Patients attend from a single center (CRO, Centro di Riferimento Oncologico) at the Gastroenterology Unit. CDH1 mutations of all 16 exons and their flanking non coding regions were analyzed by using PCR followed by direct sequencing. The frequency of CDH1 germline mutations in families with HDGC is 25-30% but the real frequency and characterization of germline variants for CDH1 in sporadic Gastric Cancer (GC) patients is not known. Moreover, recently CDH1 mutations have been demonstrated to have a prognostic role in overall GC. It is important to determine the prevalence of germline CDH1 mutations in overall patients with GC. To this end, we tested CDH1 for germline mutations in a population of patients with non-hereditary GC.

Results: Within the 142 samples screened a number of 20 mutations were found, including five which load to aminoacid replacement (non synonymous), nine synonymous variants, four intronic variants and two variant in the 5’ untranslated region (UTR). More specifically, the five non synonymous variants were: G54R, G274S, A298T, T470I and A592T, with the last present in two patients. The G54R mutation is a new variant of exon 2 and studies are going to test the pathogenicity of the mutation.

Conclusion: The frequency of non synonymous CDH1 mutations in our series was 5 out of 142 cases (3.5 %). The pathogenesis and prognostic effect of these mutations in patients with GC are in course.). More specifically, the five non synonymous variants were: G54R, G274S, A298T, T470I and A592T, with the last present in two patients. The G54R mutation is a new variant of exon 2 and studies are going to test the pathogenicity of the mutation.

Disclosure of Interest: None declared

P1175 FACTORS OF CLINICAL SUCCESSFUL PLACEMENT OF SELF EXPENDABLE METAL STENT IN MALIGNANT GASTRIC OUTLET OBSTRUCTION

J. Dong Il¹, K. Dae Hwan¹, K. Hyung Wook¹, C. Cheol Woong¹, P. Su Bum¹, K. Su Jin¹

¹Internal Medicine, Pusan National University, Yangsan Hospital, Yangsan, Korea, Republic Of

Contact E-mail Address: gon22gon@naver.com

Introduction: There are several reports of superiority of self expandable metal stent (SEMS) placement over surgery in symptom relief and shorter hospital stay in malignant gastric outlet obstruction (GOO). However, there is significant difference between technical and clinical success rate of placement of SEMS placement. So, we investigated factors associated with clinical success on the placement of SEMS.

Aims & Methods: We analyzed retrospectively medical records of 124 patient who received endoscpoic placement of SEMS due to malignant GOO from February 2009 to June 2014 in Pusan national university Yangsan Hospital. The change of the Gastric Outlet Obstruction Scoring System (GOOSS) before and after the procedure was investigated. Then we analyzed some factors associated with the improvement of GOOS.

Results: The rate of techinical success of placement of SEMS was 98%(122/124). Clinical success of placement of SEMS was defined as improvement of GOOSS within 7 days after stent placement and it was 81.1% (99/122). Causes of stenosis were stomach cancer 39 (32%), pancreatic cacer 37 (30.3%), cholangiocarcinoma 20 (16.4%), ampulla of vater cancer 8(6.6%), gall bladder cancer 18 (14.7%). We reviewd variables related to improvement of GOOSS and identified some factors such as ECOG ≥ 3 (Adjusted OR 9.9, p = 0.001), gall bladder cancer (Adjusted OR 9.201, p = 0.011), carcinomatosis peritonei (Adjusted OR 33.11, p < 0.001) and impossibility of passing the endoscope through obstructive site (Adjusted OR 6.743, p = 0.037).

Conclusion: We realized some factors of clinical success in placement of self expandable metal stent in malignant GOO. Physician should take into account of these factor.

Disclosure of Interest: None declared

P1176 CLINICAL OUTCOME OF NONAMPULLARY DUODENAL NEUROENDOCRINE TUMORS DIAGNOSED AS G1 AND G2 CATEGORIES

S. Nonaka¹, I. Oda¹, H. Taniguchi², M. Sekiguchi², Y. Miyamoto², K. Hiroki², S. Abe¹, H. Suzuki¹, S. Yoshinaga¹, Y. Saito¹

¹Endoscopy Division, ²Pathology Division, National Cancer Center Hospital, Tokyo, Japan

Contact E-mail Address: snonaka@ncc.go.jp

Introduction: The gastrointestinal tract is the most frequent site for neuroendocrine tumors (NETs). Duodenal NET is rare and occurs less frequently than gastric and rectal NETs. The surgical resection is a standard treatment for T2 duodenal NET invading into muscle layer or indicating more than 1cm in size. However, the endoscopic resection (ER) has the possibility to cure T1 duodenal NET invading within submucosal layer (SM) and 1cm or less in size because of a low frequency of lymph node and distant metastasis.

Aims & Methods: The aim of this study was to analyze the clinical outcomes of patients with duodenal NET and to assess the indication for ER as a curative procedure in selected cases. We included 47 consecutive patients with 49 lesions who were diagnosed to have nonampullary duodenal NETs as G1 and G2 categories of WHO classification between May 1997 and June 2014 in our hospital. Patients who underwent only chemotherapy were excluded from this study as well as patients diagnosed with ampullary NET. We analyzed patient characteristics, endoscopic findings, treatment methods, complications, pathological results and long-term outcomes.

Results: Male/female, 32/15; mean age, 65.2; 1st/2nd/3rd part, 42/6/1; single/multiple, 45/2; median tumor size in cases of ER/surgery, 5mm (range, 3-10)/10mm (1-40). 38 lesions were recognized as an elevation in the submucosal tumors and the finding of the delle was positive in 17 lesions endoscopically. Twenty-one patients with 22 lesions underwent ER including 7 endoscopic submucosal dissections and 15 endoscopic mucosal resections. The tumor depth was limited to SM in all lesions histopathologically. The proportions of positive lesions for vertical margin were 13% (5/7) for 5mm in size or less and 71% (2/15) for 6mm or more, and 2 patients received the additional surgery after ER. Twenty patients with 21 lesions, involving 2 cases with additional surgical resection, underwent surgery including local excision of the duodenum for 8 patients, distal gastrectomy for 8, total gastrectomy for 3, and pylorus preserving pancreaticoduodenectomy for 2. Eight lesions were incidentally detected in the surgical specimen. Eight patients were carefully followed up for various reasons. Lymph node metastasis (LNM) were positive histopathologically among 6 out of 20 surgical patients and all the lesions had the finding of the delle. Three lesions that invaded into muscle layer or deeper were 12-40mm in size and were diagnosed as G2 category with Ki-67 labeling index 3% or more. The remaining 3 limited into SM were 10mm or less in size and were diagnosed as G1 category with Ki-67 labeling index less than 3%. In the group of 39 patients treated endoscopically or surgically, there were no LMN (0/23) in T1 cases negative for the finding of the delle, 8.6% (3/35) in cases of G1 category and 9.7% (3/31) in T1 cases regardless of the finding of the delle. In 1 patient, second surgery was performed for the metachronous LNM 47 months after the initial operation. There were no death from duodenal NET and no recurrence of liver metastasis during 42 months of the median follow-up.

Conclusion: Surgical resection is basically recommended for nonampullary duodenal NET, however ER can be considered for T1 lesions without the finding of the delle and 5mm or less in size.

Disclosure of Interest: None declared

TUESDAY, OCTOBER 27, 2015   09:00-17:00

H. PYLORI II – HALL 7__________

P1177 HELICOBACTER PYLORI INFECTION IN A POPULATION OF OBESE PATIENTS PROPOSED FOR BARIATRIC SURGERY

A. Vaz¹, M. Eusebio¹, A. Antunes¹, T. Gago¹, P. Queirós², M. Sanchez³, T. Sanai³, J. Teixeira³, R. Ornelas¹, H. Guerreiro¹

¹Gastroenterology, Centro Hospitalar do Algarve , Faro, ²Gastroenterology, Centro Hospitalar do Algarve , Portimão, ³Surgery, Centro Hospitalar do Algarve, Faro, Portugal

Contact E-mail Address: anam_vaz@hotmail.com

Introduction: The estimated prevalence of Helicobacter Pylori (H.P.) in the Portuguese population is about 80%. Due to its ulcerogenic and carcinogenic potential, the screening and eradication of this bacteria before bariatric surgery has become common practice. Recently, the relation between H.P and multiple metabolic disorders has been deserving attention from the scientific community.

Aims & Methods: Our aim was to evaluate the prevalence of H.P. and its relation with metabolic comorbidities in obese patients. We did a retrospective study of patients who performed upper endoscopy before being submitted to bariatric surgery between January 2012 and December 2014.

Results: A total of 200 patients were included, 90% females with a mean age of 44.2 ±11.2 years, weight 109.6 ± 18.2 Kg and Body Mass Index (BMI) 42.2 ± 4.9 Kg/m². As for metabolic comorbidities, Hypertension was present in 58% of patients, Hypercholesterolemia in 57.5%, Hypertriglyceridemia in 23.5% and type 2 Diabetes Mellitus in 28%. The prevalence of H.P in this population was 58%, with diagnosis made by endoscopic biopsy (histology or rapid urease test) in 109 patients (94%) and in the remaining through fecal antigen test. There was no significant correlation between the presence of dyspeptic symptoms, endoscopic or histologic findings, weight, BMI or age and testing positive for H.P. Concerning the metabolic comorbidities previously referred, there was a significant relation between altered cholesterol values and infection with H.P (p < 0.05). Twelve patients (6%) had postoperative complications, but there was no statistical association with H.P infection.

Conclusion: We have verified a lower prevalence of H.P. infection in obese patients when compared to the general population, as well as a statistical relation between hypercholesterolemia and the presance of infection. The eradication of this pathogen in obese patuients may therefore play a role in improving these patients’ lipid profile.

Disclosure of Interest: None declared

P1178 INVERSE RELATIONSHIP BETWEEN HELICOBACTER PYLORI INFECTION AND ASTHMA

J. H. Lim¹², N. Kim²³, S. H. Lim¹², J. S. Kim¹², H. C. Jung²

¹Seoul National University Hospital Healthcare System Gangnam Center, ²Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, ³Seoul National University Bundang Hopital, Seongnam, Korea, Republic Of

Contact E-mail Address: limz00@gmail.com

Introduction: Recent studies suggested that Helicobacter pylori could prevent allergic disease, especially in the children. However, there are debates in the adults.

Aims & Methods: The aim of this study is to clarify the true association between H. pylori infection and asthma in a population with high prevalence of H. pylori in the age over 16 years. Medical records of subjects who received health surveillance checkup between January 2005 and December 2011 were reviewed. Their serum H. pylori IgG status, H. pylori eradication history, and history of asthma or other allergic conditions, such as allergic rhinitis, atopic dermatitis, chronic urticarial, food/drug allergy, and others were analyzed. Those who had H. pylori IgG or H. pylori eradication history were considered to have H. pylori infection. Information about patients’ history of asthma or other allergic conditions was obtained from their questionnaire and medical records.

Results: Out of the total 15,999 patients, 9,662 had history of H. pylori infection, 376 had asthma, and 3,530 had other allergic conditions than asthma. H. pylori infection was positively related with age (OR 1.052, 95% CI: 1.049-1.055, p < 0.001). Among the total, H. pylori infection and asthma demonstrated no significant association (OR 1.031, 95% CI: 0.829-1.282, p = 0.783). However, among those under 50 years old, H. pylori was inversely associated with asthma with statistical significance (OR 0.649, 95% CI: 0.453-0.931, p = 0.018). Other allergic conditions than asthma also showed inverse relationship with H. pylori infection among the total (OR 0.923, 95% CI: 0.854-0.999, p = 0.047).

Conclusion: The inverse association between H. pylori infection with asthma or other allergic conditions in young population suggests underlying immune mechanism by H. pylori infection inhibits some allergic reaction in the adults.

Disclosure of Interest: None declared

P1179 GASTRIC JUICE POLYMERASE CHAIN REACTION (PCR) FOR THE DIAGNOSIS OF HELICOBACTER PYLORI INFECTION IN PATIENTS WITH UPPER GASTROINTESTINAL BLEEDING: COMPARISON WITH OTHER CLASSICAL DIAGNOSTIC METHODS

A. Sirinawasatien¹, S. Chandrasakha¹, P. Hansombun¹

¹Department of Medicine, Rajavithi Hospital, Bangkok, Thailand

Contact E-mail Address: sui_apichet@yahoo.com

Introduction: The prevalence of H. pylori infection is approximately 70% in patients with peptic disease.¹ Many studies have demonstrated that rapid urease test and histology lack sensitivity for a bleeding peptic ulcer.^2,3 Gastric juice PCR has better accuracy for diagnosis of H. pylori infection than histology in a non-bleeding peptic ulcer.⁴ However, there is a lack of data for patients with UGIB.

Aims & Methods: To determine the diagnostic efficacy of gastric juice PCR for the detection of H. pylori infection compared to histology, rapid urease test and culture in patients with UGIB. Sixty-four patients who presented with UGIB and were undergoing upper GI endoscopy between 1 January, 2015 and 31 March, 2015 were enrolled consequetively. Gastric biopsy specimens from the corpus and antrum were taken for rapid urease test, histology (hematoxylin and eosin) and culture. Five milliliters of gastric juice was aspirated by a sterile ERCP catheter via the endoscope working channel. The sample was evaluated by agarose gel electrophoresis and Southern blot hybridization for the 23S rRNA gene of H. pylori. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, positive and negative likelihood ratio for gastric juice H. pylori PCR were compared to histology, rapid urease test and culture.

Results: Of 64 patients, 41 were male and 23 were female. The mean age was 59 years. There were 53.1% of patients who presented with melena, 26.6% with hematemesis, and 20.3% with both melena and hematemesis. The means of Rockall and Blatchford scores were 2.52 and 11.23, respectively. Endoscopic findings showed lesion at stomach in 51 patients, duodenum in 6 patients and in both stomach and duodenum in 7 patients. The most common cause was peptic ulcer (60%). The prevalence of H. pylori infection, either positive culture or positive rapid urease test plus histology, was 43.8%. The sensitivity of gastric juice PCR for H. pylori was significantly higher than histology (92.9% vs 25%, P <0.001) but equal to rapid urease test (92.9%) and culture (96.4%). Further analysis showed a non-significant difference in the sensitivity of rapid urease test, culture and gastric juice PCR for H. pylori between patients with and without blood in the stomach (47% and 53%, respectively).

Conclusion: Gastric juice PCR for H. pylori is highly sensitive for diagnosing H. pylori infection in patients with upper gastrointestinal bleeding. It is non-invasive, non-biopsy-based test.

Disclosure of Interest: None declared

P1180 REAL-WORLD HELICOBACTER PYLORI DIAGNOSIS IN PATIENTS REFERRED FOR ESOPHAGODUODENOSCOPY: THE GAP BETWEEN GUIDELINES AND CLINICAL PRACTICE

D. Shirin¹, S. Matalon², B. Avidan³, E. Broide², H. Shirin¹²

¹Tel Aviv University, Tel Aviv, ²Gastroenterology, Assaf Harofeh Medical Center, Zerifin, ³Gastroenterology, Cheba Medical Center, Ramat Gan, Israel

Contact E-mail Address: haimsh@asaf.health.gov.il

Introduction: Among available tests to detect H. pylori, histopathology is the most accurate when performed correctly with unknown validity in daily practice clinic settings.

Aims & Methods: To determine the rate of potentially false negative H. pylori results that might be due to continued use of PPIs in routine endoscopy practice. We also aimed to establish whether gastroenterologists recommend routine cessation of PPIs before EGD and whether they regularly document that biopsies for H. pylori testing have been taken while the patients are on PPI treatment.

Detailed information about three known factors (PPIs, antibiotics or bismuth and prior H. pylori eradication treatment), which may cause histology or rapid urease test (RUT) to be unreliable, had been prospectively collected through interviews using a questionnaire before each test. The site and the number of the gastric biopsies that were obtained from each patient during esophagogastroduodenoscopy (EGD) were according to the local recommendations in each center. Gastric biopsies were stained with H&E for histological analysis.

Results: A total of 409 subjects at three academic Gastroenterology Institutions were tested 200 times with histology. Fifty six percent (68 of 122) of all negative tests fell in the category, of continuing PPI use, which had the potential to make the histology and RUT results unreliable.

Conclusion: These data demonstrate a clear and important gap between current guidelines and real-world practice with regards to the diagnosis of H. pylori during EGD. A negative histology or RUT should be considered false negative until potential protocol violations are excluded. In all patients documentation of PPI use during the EGD should be an integral part of the EGD report. The current practice of taking biopsies for H. pylori testing in patients under PPI, should be reevaluated.

Disclosure of Interest: None declared

P1181 USEFULNESS OF LINKED COLOR IMAGING (LCI) FOR DIAGNOSIS OF HELICOBACTER PYLORI (H. PYLORI) INFECTION

H. Kitae¹, N. Yagi¹, A. Tomie¹, Y. Oshima¹, A. Obora¹, T. Kojima¹

¹Gastroenterology, Murakami Memorial Hospital, Asahi University, Gifu-shi, Japan

Contact E-mail Address: hkitae@koto.kpu-m.ac.jp

Introduction: LCI is a novel image-enhanced endoscopy with a laser light source to enhance the slight difference in mucosal color. That is, LCI performs expansion and reduction of color information simultaneously so that a reddish color become redder, and a whitish color become whiter. Approximately half of the world's population is infected with H. pylori. It is now well known that H. pylori infection induce duodenal and gastric ulcer disease and gastric cancer. Diffuse redness of fundic mucosa was one of the most important endoscopic features of H. pylori infection. We expected LCI to enhance the diffuse redness in H. pylori-positive patient, and to facilitate the endoscopic diagnosis of H. pylori infection.

Aims & Methods: The aim of this study is to evaluate the usefulness of LCI for diagnosis of H. pylori infection compared to the conventional endoscopy with white-light image (WLI). We retrospectively analyzed 134 patients with H. pylori infection and 126 patients with negative H. pylori infection those were examined with WLI and LCI at Murakami Memorial Hospital Asahi University from July 2014 to April 2015. We performed the definitive diagnosis of H. pylori infection using several methods. Two endoscopists (A: an expert involved in the development of LCI, B: a senior resident) evaluating all of the endoscopic WLI and LCI images, divided patients into H. pylori-positive group and H. pylori-negative group. Additionally we divided patients in each groups into highly-suggestive (HS) and lower-suggestive (LS) sub-groups.

Results: The levels of accuracy / sensitivity / specificity of diagnosis of H. pylori infection by A using WLI, and LCI were 75.8% / 68.7% / 83.3%, and 83.8% / 83.6% / 84.1%, respectively. On the other hands, those of diagnosis by B using WLI, and LCI were 73.5% / 86.6% / 55.1%, and 81.5% / 95.5% / 77.7%, respectively. The accuracy and sensitivity of diagnosis with LCI was significantly higher than those of WLI by two endoscopists (p < 0.05). There were no difference between the specificity of diagnosis by WLI and LCI. The kappa value of variability between A and B for LCI (kappa value = 0.635) was higher than that for WLI (kappa value =0.488). The ratio of HS group to LS group among patients correctly diagnosed using LCI is significantly greater than when it is diagnosed using WLI (p < 0.01).

Conclusion: LCI is valuable tool for diagnosis of H. pylori infection compared to WLI. LCI has the high accuracy and sensitivity of diagnosis of H. pylori infection. When it is suspected H. pylori infection using LCI, it needs to be carefully diagnosed using appropriate methods, because the consensus is that it should be eradicated as soon as possible and best before pre-cancerous lesions are present.

Disclosure of Interest: None declared

P1182 A SIGNIFICANT INCREASE OF PEPSINOGEN I/II RATIO IS A RELIABLE BIOMARKER FOR SUCCESSFUL HELICOBACTER PYLORI ERADICATION; A SINGLE INSTITUTE EXPERIENCE IN JAPAN

H. Osumi¹, J. Fujisaki¹, T. Suganuma², M. Igarashi¹, K. Miki¹

¹Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, ²Department of Gastroenterology, Iida Municipal Hospital, Nagano, Japan

Contact E-mail Address: hiroki.osumi@jfcr.or.jp

Introduction: Heretofore, there were many reports about the evaluation criteria of eradication therapy for Helicobacter pylori (H.pylori) using pepsinogen. Almost all reports were based on the percentage changes in serum PG before and after eradication therapy. In addition, the evaluation criteria using multi cut-off level was higher accuracy than the evaluation criteria using mono cut-off revel. If we could evaluate H.pylori eradication using serum PG, it is convenient and cost-effective compared to ¹³C-urea breath test.

Aims & Methods: The aim of this study was to evaluated usefulness as the evaluation criteria using the percentage changes in serum PGI/II ratios of eradication therapy for H.pylori. A total of 650 patients received eradication therapy from October 2008 to March 2013 and we could measure serum pepsinogen I (PGI) and pepsinogen II (PGII) levels in 562 cases with H.pylori infection before and after eradication therapy. We also determined percentage changes in serum PGI: PGII ratios before and 3 months after the treatment by CLEIA (FUJIREBIO Inc, Tokyo, Japan) and established cut-off values for them to distinguish success from failure of H.pylori eradication. Cut-off values for percentage changes in serum PGI: PGII ratios were set as +40%, +25%, and + 10% when the serum PGI:PGII ratios before treatment were less than 3.0, not les than 3.0 but less than 5.0 and not less than 5.0, respectively. The percentage change in values were calculated as follows: percentage change= {(value 3 months after end of the treatment) –(value before treatment )}/(value before treatment)×100²⁾. Gold standard of H. pylori eradication was defined as a negative by the use of a ¹³C-urea breath test performed 3 months after completion of the eradication treatment. The statistical significance of serum levels of PGI, PGIIand PGI:PGIIratios as function of the eradication status was determined by Student’s t test. Findings of p<0.05 were taken to indicate statistical significance.

Results: Patients characteristics were as follows: 562 patients (226 males 40.3%, 336 females 59.7%) with a mean age of 62 ± 10 yr. The ratios of first, second, third line eradication treatment were 77.9% (438/562), 19.9% (112/562), 2.2% (12/562), respectively. Eradication of H. Pylori was achieved in 433 cases (77.0%). There were no significant differences serum level of PGI, PGII, and PGI:PGIIratios before eradication treatment between the eradication success group and failure group. (PGI:55.0 ± 30.6 vs 57.9 ± 30.2, PGII: 24.7 ± 12.1 vs 24.9 ± 12.8, PGI/II: 2.3 ± 1.0 vs 2.4 ± 0.9, p=n.s) On the other hand, there was were significant differences of each factors after eradication treatment.(PGI: 33.6 ± 19.6 vs 54.2 ± 26.7, PGII: 7.5 ± 3.5 vs 23.3 ± 12.2, PGI/II: 4.5 ± 1.6 vs 2.5 ± 1.1, p<0.05) Increasing percentage in serum levels of PGI:PGIIratios after treatment compared with the values before treatment clearly distinguished success from failure of eradication. (108.2 ± 57.2 vs 6.8 ± 30.7, p<0.05) Using above cut-off values, the sensitivity (non-eradication: H.pylori+), specificity (eradication: H.pylori -), and validity for determination of H.pylori were 93.1, 93.8 and 93.2%, respectively.

Conclusion: In conclusion, our findings suggested that the percentage changes in serum PGI/II ratios are useful as the evaluation criteria of eradication therapy for H. pylori.

Disclosure of Interest: None declared

P1183 THE HELICOBACTER ERADICATION ASPIRIN TRIAL (HEAT): A LARGE SIMPLE RANDOMISED CONTROLLED TRIAL USING NOVEL METHODOLOGY IN PRIMARY CARE

J. S. Dumbleton¹, A. Avery², C. Coupland², F. D. R. Hobbs³, D. Kendrick², M. V. Moore⁴, C. Morris⁵, G. P. Rubin⁶, M. D. Smith⁷, C. J. Hawkey¹

¹Nottingham Digestive Diseases Centre, ²Department of Primary Care, University of Nottingham, Nottingham, ³Department of Primary Care, University of Oxford, Oxford, ⁴Department of Primary Care, University of Southampton, Southampton, ⁵TCR Nottingham Ltd, Nottingham, ⁶Department of Primary Care, University of Durham, Durham, ⁷School of Pharmacy, University of Nottingham, Nottingham, United Kingdom

Contact E-mail Address: jennifer.dumbleton@nottingham.ac.uk

Introduction: Clinical trials measuring the effect of an intervention on clinical outcomes are more influential than those investigating surrogate measures but are costly. We developed methods to reduce costs substantially by using existing data in primary and secondary care systems, to ask whether Helicobacter pylori eradication would reduce the incidence of hospitalisation for ulcer bleeding in aspirin users.

Aims & Methods: The Helicobacter Eradication Aspirin Trial (HEAT) is a HTA-funded, CRN-supported, double-blind placebo controlled randomised trial of the effects of H. pylori eradication on subsequent ulcer bleeding in infected individuals taking aspirin daily, conducted in practices across the whole of England, Wales and Northern Ireland. A bespoke web-based trial management system developed for the trial (and housed within the secure NHS N3 Data Network) communicates directly with the HEAT Toolkit software downloaded at participating practices, which issues MIQUEST queries searching entry criteria (≥60 years, on chronic aspirin ≤325mg daily, not on anti-ulcer therapy or non-steroidal anti-inflammatory drugs) for GP review of eligibility. Trial participation is invited using a highly secure automated on-line mail management system that ensures patients receive an invitation within 48 hours. Interested patients are seen once for consent and breath testing. Those with a positive test are randomised to eradication treatment (lansoprazole, clarithromycin, metronidazole) or placebo with drug sent by post. Events are tracked by upload of accumulating information in the GP database, patient contact, review of national Hospital Episode Statistics and ONS data.

Results: HEAT is the largest CRN CTIMP trial, with 105,276 invitation letters sent from 772 practices, 20,509 volunteers, and 2,847 H. pylori positive patients randomised to active or placebo treatment after 2.5 years of recruitment. 178 practices have performed their first follow-up MIQUEST search to identify 21 potential endpoints to date.

Conclusion: HEAT is important medically, because aspirin is so widely used, and methodologically, as a successful trial would show that large-scale studies of important clinical outcomes can be conducted at a fraction of the cost of those conducted by industry, which in turn will help to ensure that trials of primarily medical rather than commercial interest can be conducted successfully in the UK.

Disclosure of Interest: None declared

P1184 COMPARISON OF NON-INVASIVE TESTS; STOOL HPSA ELISA AND C13UREA BREATH TEST IN THE DIAGNOSIS OF HELICOBACTER PYLORI INFECTION IN A LOW PREVALENCE COHORT

J. A. Omorogbe¹, D. Brennan¹, S. Smith¹, M. Alsaffar², D. Mcnamara¹, on behalf of Trinity Academic Gastroenterology Group

¹Clinical Medicine, ²Trinity College Dublin, Dublin, Ireland

Contact E-mail Address: joeamaen@gmail.com

Introduction: Non-invasive testing for H. pylori infection has allowed for cost effective and safer ways to diagnose infection in both primary care and hospital settings. The reduced prevalence of H. pylori infection in the Irish population in keeping with other developed nations, can negatively impact on the diagnostic accuracy of a given test. Frequent evaluation and comparison of commercially available tests has been recommended and should be performed to ensure that the most sensitive and specific are used in clinical practice.

Aims & Methods: To evaluate and compare two non-invasive H. pylori tests; premier platinum HpSA and C¹³UBT in an Irish cohort. Adult patients referred for a C¹³UBT at the Adelaide and Meath Hospital were prospectively recruited. Patients on recent antibiotics, regular PPI or who had previously received a course of eradication therapy were excluded. Following informed consent patients were asked to collect and bring in a stool sample on the day of their C¹³UBT testing. HpSA ELISA testing was carried out in accordance with manufacturer’s instructions (Meridian Biosciences, Germany). An absorbance cut off of ≥0.140 (at 450nm) was considered positive. C¹³ UBT was considered as the gold standard and a delta value of ≥4% was deemed positive.

Results: To date 124 patients mean age 41 years, male gender 87(30%) have been recruited. In all 45(36%) percent where H. pylori positive on C¹³UBT. Overall the performance of HpSA was disappointing with only 29(23%) positive tests. In all there were 17 false negative and 1 false positive HpSA test. As such the sensitivity, specificity, positive and negative predictive values for HpSA compared with C¹³UBT were 62%, 99%, 97% and 82% respectively. Overall correlation between these two non-invasive tests was poor ĸ 0.13, 95% CI 0.016 – 0.242. The low sensitivity may reflect specific collection and storage requirements which are a common problem for many faecal tests.

Conclusion: HpSA performance in this study does not meet international guidelines for a diagnostic test for H. pylori infection and cannot be recommended for regular clinical use. The accuracy of UBT appears to be less affected by the relatively low prevalence of H. pylori infection in our community, however formal comparison with invasive modalities should be undertaken to assess its accuracy. C¹³UBT testing continues to remain the first line non-invasive diagnostic tool in detection of H.pylori infection.

Disclosure of Interest: None declared

P1185 DISAPPEARANCE OF DIFFUSE REDNESS AND APPEARANCE OF MAP-LIKE REDNESS ARE THE MOST IMPORTANT FINDINGS FOR DIAGNOSIS OF H. PYLORI ERADICATED STATUS

S. Terao¹, I. Kure¹, M. Tohme¹, K. Furumatsu¹, A. Nishizawa¹, S. Suzuki¹, I. Tamura¹, K. Yamashiro¹, M. Kohhashi¹, S. Hasegawa¹

¹Gastroenterology, Kakogawa West City Hospital, Kakogawa City, Hyogo Prefecture, Japan

Contact E-mail Address: s-terao@kakohp.jp

Introduction: Little has been reported on endoscopic findings related to Helicobacter pylori (Hp) eradicated case while several findings have been revealed to be useful in diagnosing Hp positive status.

Aims & Methods: To clarify the characteristic endoscopic appearance of Hp eradicated status upper GI endoscopy was performed in 446 patients with Hp positive and 297 patients proved to be negative 12 months after its treatment (women, 380; mean age, 62.4 years). Serum Hp IgG antibody level or rapid urease test were adopted to confirm Hp infection in all the cases and at least 2-site biopsy specimens were examined for histology and ¹³C UBT was performed in all the Hp treated cases. The presence or absence of the following 8 endoscopic findings were evaluated: regular arrangement of collecting venules (RAC), atrophic change, diffuse redness, spotty redness, rugal hyperplasia, mucosal swelling, exudation, map- like redness. Five well-trained endoscopists who were blinded to clinical information assessed the findings.

Results: See table.

Abstract number: P1185

	Hp positive	Hp eradicated	Total	Sensitivity	Specificity	PPV	NPV	ROC/AUC
	446	297	743					95% CI
RAC +	34	21	55	92.9%	6.6%	60.0%	38.2%	75.4%
RAC-	412	276	688					0.707-0.800
Atrophic change +	405	270	675	90.8%	9.1%	60.0%	39.7%	49.8%
Atrophic change -	41	27	68					0.456-0.540
Diffuse redness +	440	1	441	98.7%	99.7%	99.8%	98.0%	99.0%
Diffuse redness -	6	296	302					0.983-0.998
Spotty redness +	226	42	268	50.7%	85.9%	84.3%	53.7%	68.3%
Spotty redness -	220	255	475					0.645-7.721
Rugal hyperplasia +	204	217	421	45.7%	26.9%	48.5%	24.8%	35.9%
Rugal hyperplasia -	242	80	322					0.319-0.399
Mucosal swelling +	56	24	80	12.6%	91.9%	70.0%	41.2%	51.7%
Mucosal swelling -	390	273	663					0.475-0.559
Exudation +	229	3	232	51.3%	99.0%	98.7%	57.5%	75.1%
Exudation -	217	294	511					0.717-0.785
	Hp eradicated	Hp positive
Map-like redness +	207	8	215	69.7%	98.2%	96.3%	83.0%	84.0%
Map-like redness -	90	438	528					0.806-0.873

Diffuse redness, which had been generally observed in patients with Hp positive cases, was almost totally disappeared after Hp eradication. In contrast, map-like redness appeared in approximately 70% of patients with Hp eradicated status.

Conclusion: Disappearance of diffuse redness is the most important and decisive finding and map-like redness appearance is also beneficial to diagnose Hp eradicated status.

Disclosure of Interest: None declared

P1186 RELATIONSHIP BETWEEN SERUM PEPSINOGENS AND GASTRITIS SCORES BASED ON KYOTO-CLASSIFICATION OF GASTRITIS

T. Furuta¹, M. Sugimoto², S. Sahara², H. Ichikawa², T. Kagami², Y. Hamaya³, M. Iwaizumi², S. Osawa⁴, K. Sugimoto²

¹Center for Clinical Research, ²First Department of Medicine, ³Department of Clinical Oncology, ⁴Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

Contact E-mail Address: tafuruta@fd6.so-net.ne.jp

Introduction: Serum pepsinogens (PGs) reflect the atrophy and inflammation of gastritis induced by H. pylori infection. Recently, Kyoto-classification of gastritis has been developed and used widely.

Aims & Methods: The aim of the study was to investigate the relationship between Kyoto-classification of gastritis and serum PGs.

A total of 283 patients who underwent gastroscopy were enrolled. Serum levels of PG I and PG II were measured. Of the parameters of Kyoto-classification of gastritis, atrophy (C0-CII:A0, CII-C-III:A1, and OI-OIII:A2), intestinal metaplasia (None:I0, within antrum:I1 and up to corpus:I2), hypertrophy of gastric fold (-:H0, +: H1), nodular gastritis (-:N0, +:N1) and diffuse redness (-:DR0, mild: DR1, severe:DR2) were scored based on endoscopic findings.

Results: Mean PGI levels of A1, A2 and A3 groups were 67.7, 68.9 and 50.0 (ng/ml), respectively (P < 0.001). Those of PG II were 15.2, 26.1 and 23.8 (ng/ml), respectively (P < 0.001). Therefore, the expansion of gastric atrophy can be estimated by PGI and PG II. The PG I/PG II ratios in I0 and I1 gorups were 3.0 and 2.2, respectively (P < 0.001). Therefore, presence of intestinal metaplasia can be estimated by measurements of PG I/PG II ratios. In H0 and H1 groups, mean PG I levels were 56.8 and 65.2 (ng/ml), respectively, those of PG II were 21.1 and 32.1 (ng/ml), respectively and those for PG I/PG II were 3.0 and 2.2, respectively (P < 0.001), suggestion that hypertrophy of gastric folds are related to severe inflammation of gastric mucosa. Nodular gastritis were observed more often in females. Means of PG I, PG II and PG I/PG II in patients with nodular gastritis were 66.2 (ng/ml), 24.4 (ng/ml) and 2.9, respectively, suggesting that nodular gastritis is tempted to be induced in female patients with severe gastric inflammation but mild atrophy. The total score was significantly correlated with PG I/PG II. After eradication of H. pylori, the mean of PG I decreased from 61.1 to 37.2 (P < 0.001), that of PG II decreased from 25.0 to 9.0 (P < 0.001) and PG I/PG II ratios increased from 2.7 to 4.5 (P < 0.001). The mean of total gastritis score also decreased from 4.6 to 2.5 (P < 0.001).

Conclusion: We confirmed that serum PGs reflects the gastric atrophy as well as inflammation. Kyoto classification of gastritis is implicated with not only atrophy but also inflammation and is well correlated with serum PGs.

Disclosure of Interest: None declared

P1187 THE EFFECTS OF HELICOBACTER PYLORI ERADICATION THERAPY FOR CHRONIC IDIOPATHIC THROMBOCYTOPENIC PURPURA

J. J. Hwang¹, D. H. Lee¹, H. Yoon¹, C. M. Shin¹, Y. S. Park¹, N. Kim¹

¹Department of Internal medicine, Seoul National University Bundang Hospital, Seongnam, Korea, Republic Of

Contact E-mail Address: frontierassa@hanmail.net

Introduction: The aim of this study was to evaluate the ability of Helicobacter pylori eradication treatment for increasing platelet counts in patients in Korea with chronic idiopathic thrombocytopenic purpura (ITP).

Aims & Methods: The medical records of patients diagnosed with chronic ITP were retrospectively reviewed between January 2003 and December 2013. All patients were assessed for H. pylori infection using a 13C-urea breath test, and those with a positive result received standard triple therapy. A total of 102 patients were evaluated against two criteria. First, those diagnosed with H. pylori infection in whom eradication was successful were assigned to the H. pylori-positive and -eradicated group (n = 39), while those diagnosed with H. pylori infection in whom eradication failed were assigned to the H. pylori-positive and -non-eradicated group (n = 3) and those without H. pylori infection were assigned to the H. pylori–negative group (n = 60). Second, those with complete remission in whom the platelet recovery effect was maintained over the average follow-up period of 6 months after eradication therapy were defined as the responder group (n = 58), while those with partial or no response were defined as the non-responder group (n = 44).

Results: Platelet counts of the H. pylori-positive and -eradicated group increased significantly 6 months after eradication therapy compared to those of the H. pylori-positive and -non-eradicated group and H. pylori-negative group (43.2 ± 29.1 to 155.3 ± 68.7 × 103/μL vs. 42.5 ± 28.1 to 79.8 ± 59.7 × 103/μL vs. 43.1 ± 28.9 to 81.2 ± 62.2 × 103/μL, p = 0.041). The eradication therapy success rate in the responder group was 100.0% (39/39) versus that of the non-responder group (0.0%; 0/3) (p < 0.001).

Conclusion: Platelet counts of the H. pylori-positive and -eradicated group increased significantly 6 months after eradication therapy compared to those of the H. pylori-positive and -non-eradicated group and H. pylori-negative group. H. pylori eradication therapy was related to increasing platelet count, and successful eradication affected the increased platelet count in patients in Korea with chronic ITP.

Disclosure of Interest: None declared

P1188 COMPARISON OF EFFICACY OF MOXIFLOXACIN-BASED SEQUENTIAL THERAPY AND HYBRID THERAPY AS FIRST-LINE ERADICATION REGIMEN FOR HELICOBACTER PYLORI INFECTION

J. J. Hwang¹, D. H. Lee¹, H. Yoon¹, C. M. Shin¹, Y. S. Park¹, N. Kim¹

¹Department of Internal medicine, Seoul National University Bundang Hospital, Seongnam, Korea, Republic Of

Contact E-mail Address: frontierassa@hanmail.net

Introduction: The aim of this study was to evaluate the efficacy of 14-day moxifloxacin-based sequential therapy compared with 14-day hybrid therapy as a first-line eradication treatment of Helicobacter pylori infection.

Aims & Methods: From August 2014 to January 2015, 284 patients with confirmed H. pylori infection randomly received 14days of moxifloxacin-based sequential (MSQT group, n = 140) or hybrid (Hybrid group, n = 144) therapy. Successful eradication therapy for H. pylori infection was defined as a negative 13C-urea breath test 4 weeks after the end of eradication treatment.

Results: The eradication rates by intention-to-treat (ITT) analysis were 91.4% (128/140; 95% confidence interval [CI]: 90.2-92.9%) and 79.2% (114/144; 95% CI: 77.3-80.7%) in the MSQT and Hybrid groups, respectively (p = 0.013). The eradication rates by per-protocol (PP) analysis were 94.1% (128/136; 95% CI: 92.9-95.6%) and 82.6% (114/138; 95% CI: 80.6-84.1%) in the MSQT and Hybrid groups, respectively (p = 0.003). Compliance was good in both groups (MSQT/ Hybrid group: 100%/100%). The adverse event rates were 11.8% (16/136) and 19.6% (27/138) in the MSQT and Hybrid group, respectively. (p = 0.019).

Conclusion: The eradication rates were 91.4% and 79.2% in the MSQT and Hybrid groups by intention-to-treat (ITT) analysis. The eradication rates by per-protocol (PP) analysis were 94.1% and 82.6% in the MSQT and Hybrid groups. The 14-day moxifloxacin-based sequential therapy is effective and, moreover, shows excellent compliance and safety compared with the 14-day hybrid therapy.

Disclosure of Interest: None declared

P1189 1-WEEK AND 2-WEEK MOXIFLOXACIN-CONTAINING TRIPLE THERAPIES FOR SECOND-LINE ERADICATION OF HELICOBACTER PYLORI INFECTION AFTER NON BISMUTH QUADRUPLE SEQUENTIAL AND CONCOMITANT TREATMENT FAILURE

J. H. Lim¹, D. H. Lee²

¹Internal Medicine, Incheon Sarang Hospital, Incheon, ²Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea, Republic Of

Contact E-mail Address: medfd@naver.com

Introduction: PPI-based standard triple therapy for Helicobacter pylori infection has fallen considerably. To increase the eradication rate, non-bismuth quadruple sequential and concomitant therapies were introduced recently. Nevertheless, not inconsiderable patients fail to achieve eradication and need second-line treatment.

Aims & Methods: We tried to know the efficacy of moxifloxacin-containing triple therapy after non-bismuth quadruple therapy failure. A total of 98 patients who were not eradicated with non-bismuth quadruple therapy received 1-week or 2-week moxifloxacin-containing triple therapy (400 mg of moxifloxacin once daily, and 20 mg of rabeprazole and 1 g of amoxicillin twice daily). H. pylori status was evaluated 4 weeks later, after completion of treatment by ¹³C-urea breath test.

Results: 60 patients and 38 patients received 1-week and 2-week moxifloxacin-containing triple therapy, respectively. The intention-to-treat and per-protocol eradication rates were 56.7% (95% CI, 45.0-70.0) and 59.6% (95% CI, 46.6-71.7) in 1-week group, and 76.3% (95% CI, 63.2-89.5) and 80.6% (95% CI, 66.7-91.9) in 2-week group (p = 0.048, 0.036). There were no significant between-group differences, in regard to the compliance and side effects.

Conclusion: 2-week moxifloxacin-containing triple therapy showed a better efficacy than 1-week regimen after non-bismuth quadruple therapy failure. More large sample sized prospective study will be needed.

Disclosure of Interest: None declared

P1190 THE USE OF REBAMIPIDE IN COMBINATION WITH A PROTON PUMP INHIBITOR AND ANTIBIOTIC IN THE TREATMENT OF H. PYLORI-ASSOCIATED PEPTIC ULCER DISEASE: A META-ANALYSIS

J. G. E. Cataluna¹, C. A. Panlilio², F. Panjaitan², J. Bocobo³

¹Department of Medicine, St. Luke's Medical Center -Quezon City, ²Department of Medicine, ³Institute for Digestive and Liver Diseases, St. Luke's Medical Center - Quezon City, Quezon City, Philippines

Contact E-mail Address: doycataluna@yahoo.com

Introduction: Helicobacter pylori (H. pylori) resistant strains to amoxicillin, clarithromycin or metronidazole have been increasing rapidly owing to widespread use of antibiotics with proton pump inhibitors (PPI) for eradication. The standard therapy includes the use of an antibiotic with a PPI. Rebamipide, one of the gastro-protective agents in common use, has been shown to exhibit preventive or healing effects in gastric mucosa or mucosal lesion by increasing endogenous prostaglandin or by suppressing oxygen-free radicals.

Aims & Methods: A meta-analysis of randomized control trials (RCTs) was conducted to determine if the use of Rebamipide in combination with a PPI and antibiotic can augment the eradication rate of H. pylori-associated gastric inflammation in adult patients diagnosed to have peptic ulcer disease.

A literature search was performed on the PubMed database and resulted in six articles, of which four were selected. Allocation concealment, intention-to-treat analysis, completeness of follow-up and blinding of investigators, participants and outcome assessors were independently analyzed by three authors and was critically appraised with regards to methods of minimizing selection bias, performance bias, exclusion bias and detection bias. Trial results were combined under a random-effects model. Dichotomous data were analyzed by calculating the risk ratio with 95% confidence interval (CI) and a significant p value of 0.05. Subgroup analyses were performed to statistically compare subgroups. Cochrane Review Manager Software version 5.0 statistical software was used for all analyses.

Results: The primary outcome of the meta-analysis was the eradication rate of H. pylori-positive peptic ulcer disease. Across all four trials, 209 of 293 patients (71.3%) had successful eradication of H. pylori-associated peptic ulcer disease using Rebamide in combination with an antibiotic and PPI compared with 179 of 271 control group patients (66.0%). The risk ratio for the eradication rate of H. pylori-associated peptic ulcer disease in all four trials were highly consistent ranging narrowly from 0.98 – 1.31. The pooled risk ratio was 1.07 with 95% CI of 0.98-1.17.

Conclusion: There is no significant difference in the eradication of H. pylori associated peptic ulcer disease with the use of Rebamipide in addition to antibiotic and PPI compared to the standard therapy alone. However, due to the rise in resistant strains of H. pylori, there may be an increasing need to add Rebamipide to the standard therapy as it has protective effects shown to augment ulcer healing. As such, Rebamipide may still be used in peptic ulcer disease as per the discretion of the clinician.

Disclosure of Interest: None declared

P1191 DIPHENYLENEIODONIUM CHLORIDE AND PARTHENOLIDE: POTENTIAL SUBSTANCE FOR NOVEL ANTI-HELICOBACTER PYLORI AGENTS

S. Y. Kim¹, E. J. Kim¹, J.-W. Chung¹, D. K. Park¹, K. A. Kwon¹, K. O. Kim¹, Y. J. Kim¹, J. Y. Jeong²

¹Department of Gastroenterology, Gachon University, Gil Medical Center, Incheon, ²Asan Institute for Life Sciences, Seoul, Korea, Republic Of

Contact E-mail Address: breeze1212@naver.com

Introduction: Increased resistance of Helicobacter pylori (H. pylori) to antibiotics has increased the need to develop new treatments for H. pylori. Thus, there is clearly an urgent need to develop new drugs that are effective against resistant strains.

Aims & Methods: The aim of our study is to develop new substance that have an anti-H. pylori activity by using high-throughput screening assay. Chemical library composed of 1200 chemical compounds were obtained from high-throughput screening core laboratory. Antimicrobial susceptibility test was performed using the broth microdilution technique. A 96-well microtiter plates were prepared for 82 chemical compounds which showed anti-H. pylori activity in high-throughput screening assay. Among chemical compounds which showed growth inhibitory potential, potent chemical compounds for practical application were selected.

Results: Diphenyleneiodonium chloride (DPI) and parthenolide (PTL) were selected and measured minimal inhibitory concentrations (MICs) against reference and resistant strains of H. pylori. Furthermore, DPI and PTL was further evaluated to validate susceptibility against resistant H. pylori strains. The MIC value of parthenolide (PTL) and diphenyleneiodonium chloride (DPI) showed MIC value of 2.0-8.0 µg/ml and lower than 0.03 µg/ml. DPI also show antibacterial activity against common aerobic bacteria showing MICs ranges from 0.5 to 2 µg/ml.

Conclusion: This study shows that DPI could be a powerful new class of drugs against H. pylori. Further in vivo study is needed to develop this substance as anti-H. pylori drug.

Disclosure of Interest: None declared

P1192 MODIFIED SEQUENTIAL THERAPY CONTAINING LEVOFLOXACIN VERSUS LEVOFLOXACIN TRIPLE THERAPY IN THE SECOND LINE TREATMENT OF HELICOBACTER PYLORI: A RANDOMIZED TRIAL

J.-M. Liou¹, J.-Y. Wu², C.-Y. Chang³, C.-C. Chen¹, Y.-J. Fang⁴, J.-T. Lin⁵, M.-S. Wu¹, on behalf of Taiwan Gastrointestinal Disease, Helicobacter Consortium

¹Internal Medicine , National Taiwan University Hospital, Taipei, ²Kaohsiung Medical University , ³Internal Medicine , E- DA Hospital and I-Shou University, Kaohsiung , ⁴Internal Medicine , National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, ⁵School of Medicine , Fu Jen Catholic University, Taipei, Taiwan, Province of China

Contact E-mail Address: dtmed046@pchome.com.tw

Introduction: Levofloxacin triple therapy (LT) has been recommended as one of the second line eradication regimen for Helicobacter pylori (H. pylori) according to the Maastricht Consensus Report. However, recent studies showed unsatisfactory efficacy (<80%) of this regimen. Our previous pilot study showed that the eradication rate of modified sequential therapy containing levofloxacin (MS) was higher than 90%.

Aims & Methods: Therefore, we further conducted this randomized trial to compare the efficacy and tolerability of the two regimens. This open-label, randomized, multicenter trial was conducted in 9 hospitals and one community in Taiwan between 2012 and 2015. H. pylori infected subjects who failed from clarithromycin-based regimens (N ± 600) were randomized (1:1) to receive MS ((lansoprazole and amoxicillin for the first 5 days, followed by lansoprazole, levofloxacin, and metronidazole for another 5 days) or LT (lansoprazole, amoxicillin, and levofloxacin for 10 days). Successful eradication was defined as negative ¹³C-urea breath test at least 6 weeks after treatment. Our primary outcome was the eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. Antibiotic resistance was determined by agar dilution test. (ClinicalTrials.gov NCT01537055)

Results: The prevalence of clarithromycin, levofloxacin, and metronidazole resistance in this study population were 60%, 17.6%, and 36.9%, respectively. The eradication rates of MS and LT were 84.4% (249/295) and 76.3% (225/295) in the ITT analysis (p = 0.013), respectively, and 86.5% (249/288) and 79.2% (225/284) in the PP analysis (p = 0.022), respectively. There were no differences in the compliance. The efficacies in strains susceptible and resistant to levofloxacin were 92.7% (76/82) and 47.2% (9/19) for MS (p < 0.001), respectively, and were 76.4% (55/72) and 19.2% (5/26) for LT, respectively (p < 0.001). The efficacies in strains susceptible and resistant to metronidazole were 92.3% (55/59) and 83.3% (30/36) for MS, respectively.

Conclusion: Modified sequential therapy containing levofloxacin was more effective than levofloxacin triple therapy in the second line treatment for H. pylori in populations with high clarithromycin resistance.

Disclosure of Interest: None declared

P1193 RANDOMIZED TRIAL FOR HELICOBACTER PYLORI ERADICATION IN A NAIVE PORTUGUESE POPULATION - IS SEQUENTIAL TREATMENT SUPERIOR TO TRIPLE THERAPY IN REAL WORLD CLINICAL SETTING

P. Boal Carvalho¹, J. Magalhaes¹, F. Dias de Castro¹, T. Curdia Gonçalves¹, S. Leite¹, B. Rosa¹, J. Cotter¹²

¹Gastroenterology, Centro Hospitalar do Alto Ave, Guimarães, ²Life and Health Sciences Research Institute, Universidade do Minho, Braga/Guimarães, Portugal

Contact E-mail Address: pedro.n.carvalho@gmail.com

Introduction: Helicobacter pylori (HP) is the most prevalent infectious agent in the world adult population, and its eradication has become increasingly difficult as resistances to several commonly used antibiotics develop. The most adequate first-line eradication regimen for HP in Portugal has not yet been determined.

Aims & Methods: We aimed to compare HP eradication rates between triple therapy (TT) and sequential therapy (ST) in a naive Portuguese population.

Prospective randomized trial including consecutive patients with HP infection referred for first-line eradication treatment. Exclusion criteria for enrollment included previous gastric surgery or neoplasia, pregnancy or lactancy, allergy to any of the drugs. The compared eradication regimens were TT (pantoprazol 40 mg, amoxicillin 1000 mg and clarithromycin 500 mg 12/12h for 14 days) and ST (pantoprazol 40 mg 12/12h for 10 days, amoxicillin 1000 mg 12/12h during days 1-5 and clarithromycin 500 mg 12/12h, metronidazol 500 mg 12/12h during days 6-10). Eradication success was confirmed with urea breath test, and side-effects as well as the need to stop treatment were registered. Statistical analysis was performed with SPSS v21.0 and a p value < 0.05 was considered statistically significant.

Results: Of the 63 randomized patients, 3 were lost to follow-up, resulting in the inclusion of 60 patients, 39 (65%) female with mean age 52 years (SD± 14.3). Chief indications for HP eradication were functional dyspepsia (42%), premalignant gastric lesions (23%) and peptic ulcer disease (13%). TT (n=31) and ST (n=29) groups were homogeneous for gender, age and indication for treatment.

No statistical differences were encountered between ST and TT eradication rates (86.2% versus 77.4%, p = 0.379), global eradication rate was 82%.

Side-effects were reported in 10 (16.7%) patients (5 in each treatment arm), most commonly dyspepsia, diarrhea and dysgeusia. In only 2 patients, both in the ST group, treatment adhesion was irregular because of moderate dyspepsia, but in both cases, HP eradication was proven successful.

Conclusion: In this randomized controlled trial in a naive Portuguese population, we found a satisfactory global Helicobacter pylori eradication rate of 82%, with no statistical differences observed in the efficacy of the treatment between triple and sequential regiments. These results support the use of either therapy for the first-line eradication of Helicobacter pylori.

Disclosure of Interest: None declared

P1194 HIGH PREVALENCE OF SINGLE, DUAL AND MULTIDRUG RESISTANT HELICOBACTER PYLORI INFECTION AND MECHANISM OF CLARITHROMYCIN RESISTANCE IN INDIA

R. Das¹, V. Gehlot¹, S. Mahant¹, A. K. Mukhopadhyay², K. Das³⁴

¹Biotechnology, Amity Institute of Biotechnology, ²Biotechnology, National Institute of Cholera and Enteric Diseases, Noida, ³Gastroenterology, Yashoda Superspecialty Hospital, Ghaziabad, ⁴gastroenterology, Yatharth Wellness Superspeciality Hospital, Noida, India

Contact E-mail Address: rdas@amity.edu

Introduction: Antibiotic resistance to commonly used antibiotics against H. pylori is increasing very rapidly. Resistance of Helicobacter pylori to clarithromycin is associated with single base substitution in the 23S rRNA gene.

Aims & Methods: To determine antimicrobial susceptibility pattern of H. pylori strains against commonly used antibiotics in H. pylori treatment and to analyze the mechanism of clarithromycin resistanc in India.

H. pylori were cultured from 68 patients suffering from different gastro-duodenal diseases. Minimum Inhibitory concentration to different antibiotics was determined by agar dilution method. The point mutation in clarithromycin resistant strains were recognized by PCR- Restriction Fragment Length Polymorphism (RFLP) and DNA sequencing.

Results: The clinical diagnosis of 68 patients who were H. pylori culture positive were Gastro Esophageal Reflux Disease (GERD) (n=23), Nonerosive reflux Disease (NERD) (n=22), Non Ulcer Dyspepsia (NUD) (n= 13), Antral Gastritis (n=3), Duodenal ulcer (n=2) and others (n=5). Of the 68 H. pylori isolates, 29.4 % (20/68) had no resistance, the prevalence of total drug resistance was 70.6% (48/68) which includes the resistance against Metronidazole (48.5%), Furazolidone (22.1%), Amoxicillin (17.6%), Tetracycline (16.2%) and Clarithromycin (11.8%). Dual and multiple drug resistance were found in 26.5 % (18/68) and 8.9% (6/68) of cases.

In our study, A2143G point mutation in 23S rRNA gene was found in 87.5% (7/8) clarithromycin resistant strains. Another most common mutation A2142G and T2182C was found in 12.5% (1/8) clarithromycin resistant strain.

Conclusion: We conclude that more than two- third of the isolated H. pylori strains showed resistance to at least one of the antibiotics for H. pylori treatment. Metronidazole showed the maximum resistance. Emergence of dual and multi-drug resistance is of great concern and there is an urgent need for regular antibiotic resistance surveillance studies. Amoxicillin and clarithromycin based anti- H. pylori regimens commonly prescribed for triple therapy in India shows least resistance and hence appropriate for anti H. pylori management in India. To our knowledge this is the first study in India to report that the point mutation at position A2143G, A2142G and T2182C is associated with clarithromycin resistance which confirms the reports available from other parts of the world.

Disclosure of Interest: None declared

P1195 A COMPARISON OF SEQUENTIAL THERAPY WITH STANDARD TRIPLE THERAPY FOR HELICOBACTER PYLORI ERADICATION IN AN IRISH COHORT

R. B. Haider¹, S. Smith¹, J. Omorogbe¹, D. Brennan¹, B. Hall¹, G. Holleran¹, C. O’Morain¹, H. O'Connor¹, D. McNamara¹

¹Departments of Gastroenterology & Clinical Medicine Tallaght & Naas Hospital, TAGG (Trinity Academic Gastroenterology Group), Dublin, Ireland

Contact E-mail Address: bhrana@hotmail.com

Introduction: Eradication rates for the standard first line triple therapy for H. pylori infection have fallen to an unacceptably low level. Sequential therapy has been suggested as a treatment option to replace standard triple therapy. The efficacy of sequential therapy has not been assessed to date in an Irish population.

Aims & Methods: To compare the efficacy of standard triple therapy with sequential therapy for H. pylori eradication. A prospective, multicentre, randomised controlled study was conducted after ethical approval in all participating hospitals. Treatment-naïve H. pylori-infected patients (>18 years), as assessed by a positive urea breath test (UBT), were invited to participate and informed consent was obtained. Patients were randomised to receive either standard triple therapy (20 mg omeprazole, 1 g amoxicillin and 500 mg clarithromycin twice daily for 7 days) or sequential therapy (20 mg omeprazole and 1 g amoxicillin twice daily for 5 days, followed by 20 mg omeprazole, 500 mg clarithromycin and 500 mg metronidazole twice daily for 5 days). A follow-up UBT was performed 6-8 weeks post-treatment to assess treatment success.

Results: To date, 86 eligible patients (mean age: 41.7 ± 11.8 years; 64% female) who tested positive for H. pylori infection by the UBT have been recruited to the study. 90% (N ± 77) were referred for dyspepsia. A smoking habit was reported by 22% (N ± 19) of the patients. 51% (N ± 44) patients (mean age: 43.2 ± 12.6 years; 75% female) received standard triple therapy and 49% (N ± 42) patients (40.1 ± 11 years; 52% female) received sequential therapy. The eradication efficacy by intention-to-treat analysis was 56.8% (95% CI: 42.2-71.4%) for standard triple therapy and 69% (95% CI: 55.0-83.0%) for sequential therapy. In the standard triple therapy group, 2 patients did not attend for follow-up and one patient did not complete their medication due to side effects. All patients in the sequential therapy group attended for follow-up and were compliant. The eradication rates by per-protocol analysis for standard triple therapy and sequential therapy were 61% (95% CI: 46.1-76.0%) and 69% (95% CI: 95% CI 55.0-83.0%) respectively. The differences in eradication rates by either intention-to-treat or per-protocol analysis were not statistically significant. The most common adverse event reported was mild nausea at 15% (95% CI: 7.5-22.6%). Incidence in adverse events was not significantly different between the study groups.

Conclusion: Sequential therapy has a non-statistically significant advantage over standard triple therapy in our patient cohort. However, eradication rates for both standard triple therapy and sequential therapy fall considerably short of the 80% intention-to treat-rate. Further studies are required to identify potential alternatives to standard first line triple therapy.

Disclosure of Interest: None declared

P1196 CUMULATIVE HELICOBACTER PYLORI ERADICATION THERAPY IN OBESE PATIENTS UNDERGOING GASTRIC BY-PASS SURGERY

R. Cerqueira¹, M. Correia¹, H. Vilar¹, M. C. Manso²

¹Centro Hospitalar entre Douro e Vouga, Santa Maria Feira, ²University Fernando Pessoa & LAQV@REQUIMTE-UP, Porto, Portugal

Contact E-mail Address: rute.cerqueira@chedv.min-saude.pt

Introduction: The Maastricht IV Consensus Report has recently updated guidelines for the management of Helicobacter Pylori (HP) infection with special emphasis in high clarithromycin (CLT) resistance geographical areas. However, in Portugal, there are some limitations with HP eradication treatments as bismuth is not available. In line with the recommendations of the European Guidelines on surgery of severe obesity (1) and with the recommendations of the American Society of Gastrointestinal Endoscopy on endoscopy of the bariatric patient (2) we perform HP eradication in obese patients undergoing Roux-en Y gastric by-pass (RYGB) surgery.

Aims & Methods: Over a 4-year period (2011-2014), our aim was, in obese patients undergoing RY GB surgery to assess the cumulative HP eradication rates by adopting a 14 days quadruple concomitant therapy in first line treatment as proposed by the Maastricht IV consensus – proton pump inhibitor (PPI) bid, CLT 500mg bid, metronidazole (MTX) 500 bid and amoxicillin (AMX) 1000mg bid – and a 14 days second line levofloxacin based regimen – PPI bid, AMX 1000 mg bid and levofloxacin 500mg od. HP infection status was determined by histology or urea breath test and post treatment HP status was assessed by urea breath test 4-6 weeks after the end of therapy.

Results: Six hundred twenty consecutive HP-positive patients completed concomitant first-line treatment: 511 (82.4%) female, age 40.8 (±10.3) years, median age of 41 years, age range of 18-64 years. HP was eradicated in 458 patients – 73.9% (95%CI: 70.3-77.2%). In the remaining 162 patients, second-line levofloxacin based regimen eradicated HP in 95 patients – 58.6% (95%CI: 50.9 - 65.9%). These results give 89.2% (95% CI: 86.5-91.4%) cumulative eradication rates. Eradication rates were not significantly different by gender, age and smoking habits.

Conclusion: By adopting IV Maastricht guideline quadruple concomitant first-line treatment and second-line levofloxacin-based therapy high cumulative HP eradication rates are achieved but still leaves around 11% of obese patients undergoing RYGB in need of the culture and susceptibility testing prior to third-line treatment.

Disclosure of Interest: None declared

P1197 TREATMENT TRIAL RESULTS FROM COMMUNITY H. PYLORI PROJECTS IN THE CANADIAN ARCTIC

S. Veldhuyzen Van Zanten¹, A. Morse¹, K. Fagan-Garcia¹, L. Aplin¹, M. Keelan¹, S. Girgis¹, K. Goodman¹, on behalf of CANHelp Working Group

¹University of Alberta, Edmonton, Canada

Contact E-mail Address: vanzanten@ualberta.ca

Introduction: The Canadian North Helicobacter pylori (CANHelp) Working Group links northern community leaders and health officials with scientists to conduct research focused on community concerns about health risks from H.pylori infection. To date, we have initiated four community H.pylori projects: in 2007 in Aklavik, Northwest Territories (NT) (population∼600); in 2010 in Old Crow, Yukon, YT (population∼250); in 2011 in Tuktoyaktuk, NT (population∼850); and in 2012 in Fort McPherson, NT (population∼800).

Aims & Methods: The design of each community project was guided by a local planning committee. Projects components include: surveys of health and socio-environmental factors, urea breath test (UBT) screening for H. pylori infection, upper gastrointestinal endoscopy, treatment, knowledge exchange, and policy development.

We invited all H.pylori–positive participants ≥15 years to enrol in a treatment trial that randomly assigned alternate 10-day H.pylori therapies: 1) PPI-CA - the Canadian standard 3-drug therapy with a proton pump inhibitor (PPI), amoxicillin, and clarithromycin; 2) ST - sequential therapy with a PPI and amoxicillin for days 1-5, followed by a PPI, clarithromycin and metronidazole for days 6-10; 3) QT - quadruple therapy with a PPI, bismuth, metronidazole, and tetracycline. Only treatment naive participants not known to have clarithromycin-resistant H.pylori could be assigned PPI-CA, which was discontinued after initial results showed poor effectiveness. To assess infection status after treatment, we offered UBT at >=10 weeks post treatment. Each participant’s treatment outcome was classified as successful or failed according to a negative or positive UBT result, respectively.

Results: Of 921 community H.pylori project participants to date, 832 had results from H.pylori screening by UBT (positivity=60%), 323 had endoscopy with gastric biopsy, 267 enrolled in the treatment trial, and 179 had a post-treatment UBT.

Of trial participants with a follow-up UBT, treatment was successful in: 62% (29/47; 95%CI 46-75%) of those randomized to PPI-CA; 73% (65/89; 95%CI 63-82%) of those randomized to ST; 95% (39/41; 95%CI 83-99%) of those randomized to QT. If non randomized patients are also included (PPI-CA 11, ST 10 and QT 12) the cumulative success rates are: PPI-CA 62%, ST 71 % and QT 92%.

Of 205 H.pylori isolates tested for antibiotic susceptibility, 43% (88) were resistant to >=1 antibiotic: 35% (71) to metronidazole, 16% (33) to clarithromycin, 4% (8) to ciprofloxacin, 1% (2) to nitrofurantoin, 1.5% (3) to rifampicin; 0 to tetracycline or amoxicillin.

Conclusion: Treatment success estimates from this Canadian Arctic community treatment trial are imprecise due to small group sizes; however preliminary results show that QT is superior to ST and PPI-CA across communities.

Disclosure of Interest: None declared

TUESDAY, OCTOBER 27, 2015   09:00-17:00

SMALL INTESTINAL II – HALL 7__________

P1198 LINKAGE OF SMALL INTESTINAL BACTERIAL OVERGROWTH WITH IRRITABLE BOWEL SYNDROME: IS THIS AN EPIPHENOMENON OF PROTON PUMP INHIBITORS?

E. Pyleris¹, E. Giamarellos-Bourboulis², C. Barbatzas³, A. Pistiki², M. Pimentel⁴

¹Sismanogleion Hospital, Athens, ²4th Department of Internal Medicine, University of Athens, Medical School, ³sismanogleion hospital, athens, Greece, ⁴GI Motility Program, Cedars-Sinai Medical Center, Los Angeles, California, Los Angeles, United States

Contact E-mail Address: manolis.pyleris@gmail.com

Introduction: Current knowledge suggests that small intestinal bacterial overgrowth (SIBO) participates in the pathogenesis of irritable bowel syndrome (IBS). It is questionable is this association is modulated by intake of proton pump inhibitors (PPIs). We aimed to provide a clear-cut answer analyzing a big prospective cohort of patients undergoing small intestinal quantitative aerobe culture.

Aims & Methods: Duodenal aspirates were collected from 897 outpatients subjected to upper GI endoscopy and quantitatively cultured under aerobic conditions. SIBO was diagnosed as the isolation of at least one coliform ≥10³ cfu/ml. Results were correlated with history of IBS, PPI intake, type of PPI and duration of treatment, age, body mass index (BMI) and endoscopic findings. Odds ratios (OR) and 95% confidence intervals (CIs) were measured according to Mantel and Haenzel. Comparison between OR were done by the Tarone’s test. Factors independently linked with SIBO were found after forward logistic regression analysis providing ORs. Definition of a cut-off for a continuous variable to enter regression analysis was done after Receiver Operator Characteristics curve analysis with specificity greater than 90%.

Results: 158 had SIBO and 739 did not have SIBO; 20.2% and 22.2% respectively had a history of PPI intake (p: 0.558). Among patients without history of PPI intake, 123 had SIBO and 590 did not have SIBO; 56.9% and 19.0% respectively had IBS (OR: 5.63, 95%CIs: 3.76-8.5, p < 0.0001). Among patients with history of PPI intake, 35 had SIBO and 149 did not have SIBO; 65.7% and 31.5% respectively had IBS (OR: 4.16, 95%CIs: 1.91-9.06, p < 0.0001; p: 0.498 between ORs). Factors independently linked with SIBO were age ≥60 years (OR: 2.36, p: 0.001), body mass index ≥22 kg/m² (OR: 0.60, p: 0.049), presence of IBS (OR: 6.29, p< 0.0001), type 2 diabetes mellitus (OR: 1.59, p: 0.032) and endoscopic gastritis (OR: 0.47, p< 0.0001). Among patients with IBS predominant-diarrhea (IBS-D), 22.1% had history of PPI intake of more than 9 months; this was 10.1% among patients without IBS (p: 0.004). This effect was pronounced among patients reporting esomeprazole consumption (OR: 3.59, p < 0.0001).

Conclusion: The association between IBS and SIBO was completely independent from PPI intake. Long-term treatment with PPI of more than 9 months was associated with IBS-D; this was mainly an effect of esomeprazole. Although gastritis was protective against SIBO, results show that modulation of gastric pH with PPI cannot prime SIBO.

Disclosure of Interest: E. Pyleris: None declared, E. Giamarellos-Bourboulis Financial support for research: Alfa-Wassermann SpA, Italy, C. Barbatzas: None declared, A. Pistiki: None declared, M. Pimentel Financial support for research: Beatrice and Samuel A. Seaver Foundation, Consultancy: Salix Pharmaceuticals

P1199 FECAL MICROBIOTA TRANSPLANTATION FOR TREATMENT OF SLOW TRANSIT CONSTIPATION: A PROSPECTIVE OPEN-LABEL STUDY

C. Ding¹, H. Tian¹, J. Gong¹, N. Li¹

¹Research Institute of General Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China

Contact E-mail Address: dingchao19910521@126.com

Introduction: Fecal microbiota transplantation (FMT) has been proposed as a therapeutic approach for functional gastrointestinal disease (FGID). Previous studies suggested dysbiosis is frequently complicated in constipation and gut microbiota can affect gastrointestinal transit.

Aims & Methods: We launched a clinical study (NCT02301221) to examine the safety and efficacy of FMT for slow-transit constipation (STC). Twenty patients with STC, aged 20 to 74, were enrolled in this prospective open-label study. Patients received FMT on three consecutive days via nasojejunal tube with follow-up at 1, 2, 4 and 8 weeks after treatment. Bowel movements per week, Wexner Constipation Scores, Patient Assessment of Constipation Quality of Life (PAC-QOL) and adverse events were evaluated at each study visit.

Results: The rate of clinical improvement and remission based on clinical symptoms at 8 weeks postoperatively was 60% (12/20) and 35% (7/20) respectively. The patients’ spontaneous complete bowel movements (SCBMs) increased from a mean of 1.75 ± 1.27 per week pre-FMT to 4.54 ± 1.36 at 8 weeks without laxative-use (p < 0.01). Over 8 weeks, Wexner constipation scores, scored 9.75 ± 4.88 at 1 week, 7.50 ± 2.57 at 2 weeks, 7.43 ± 3.65 at 4 weeks and 7.48 ± 1.57 at 8 weeks, showed a significant reduction as compared with 14.1 ± 3.29 at pre-FMT (p < 0.01 for all comparisons). Compared with baseline, significant overall improvements were also seen in PAC-QOL scores at 1, 2, 4 and 8 weeks of follow-up (p <0.01). Meanwhile, there were no severe treatment-related adverse events during the whole FMT procedure follow-up except for venting, abdominal pain, bloating and diarrhea.

Conclusion: This is the first study to demonstrate that FMT has the potential to be somehow of help in managing patients with slow-transit constipation, but considerable further efforts are necessary to maintain a long-term effect.

Disclosure of Interest: None declared

P1200 PERINATAL ANTIBIOTIC TREATMENT ALTERS OFFSPRING’S GUT MICROBIAL PROFILE PREDISPOSING THEM TO EXPERIMENTAL COLITIS

P. Munyaka¹, A. Khafipour¹, H. Wang¹, N. Eissa¹, E. Khafipour², J.-E. Ghia³

¹Immunology, ²Animal Sciences, ³Immunology / Internal Medicine, Univeristy of Manitoba, Winnipeg, Canada

Introduction: The use of antibiotics in the perinatal period is associated with delayed microbial colonization. Postnatal maturation of the immune system is largely driven by exposure to microbes, and thus the nature of the intestinal colonization may be associated with the development of childhood diseases that may persist into adulthood, including inflammatory bowel diseases.

Aims & Methods: Therefore, we have explored whether prenatal antibiotic therapy can increase offspring susceptibility of experimental colitis through an alteration of the gut microbiota.

Pregnant C57Bl/6 mice were treated with cefazolin at 160 mg/kg body weight (bw) or with saline starting six days before the due date. At 7 weeks, male offspring from the two groups received 4% dextran sulfate sodium (DSS) in the drinking water for 5 days. Disease activity index (DAI), histology, colonic interleukin (IL)-6, IL-1β and serum C-reactive protein (CRP) were determined. From colon and fecal samples, the V3-V4 region of bacterial 16S rRNA was amplified and subjected to Illumina sequencing. Alpha-diversity was calculated using Chao 1 and beta-diversity was determined using QIIME. Differences at the genus level were determined using partial least squares discriminant analysis (PLS-DA), and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) was used for bacterial functional predictions.

Results: Prenatal ATB increased the onset of clinical disease as assessed by stool consistency, weight loss and rectal bleeding. On day 5, macroscopic and histologic scores were significantly increased. Colonic IL-6 was increased, but IL-1β levels were not changed. Conversely, in the ATB-DSS group, the CRP level was significantly decreased. In colitic mice compared to the control group, ATB significantly decreased the richness of the bacterial species in fecal samples but not in the colon, and bacterial community composition differed between the groups in both sample types, although this was further influenced by the mother. PLS-DA analysis revealed an association of specific taxa with ATB-DSS or control-DSS at lower taxonomic levels. Also, there were differences in microbial functional pathways in both fecal and colonic samples.

Conclusion: These results support the hypothesis that prenatal antibiotics modulates offspring intestinal bacterial colonization and susceptibility to develop colonic inflammation in a murine model of colitis. Furthering our understanding of the impact of prenatal antibiotics on gut bacterial colonization and susceptibility to colitis may guide future interventions to restore physiologic intestinal colonization in offspring born to antibiotic-exposed mothers.

Disclosure of Interest: None declared

P1201 SMALL INTESTINAL BACTERIAL OVERGROWTH AS A CAUSE OF SECONDARY LACTASE DEFICIENCY

N. Fadeeva¹, I. Ruchkina¹, A. Parfenov², P. Shcherbakov³, O. Knyazev¹

¹Department of Inflammatory Bowel Disease, ²Department of Inflammatory Disease, ³Department of Endoscopy, Moscow Clinical Research Center, Moscow, Russian Federation

Contact E-mail Address: chuevana@mail.ru

Introduction: Human microflora is a stable genetically determined system. Most bacteria are in the colon with their concentration reaching up to 10¹⁰–10¹¹ CFU/ml and more. The concentration of microorganisms in the small intestine fluctuates from 10¹ to10⁴ CFU/ml of the intestinal content.

Secondary lactase deficiency (SLD) is inability to digest lactose, the predominant sugar of milk. This inability results from decrease of lactase enzyme activity, which is produced in the small intestine. Purpose: to define the influence of SIBO in patients with SLD in adult patients.

Aims & Methods: : In this study, 386 patients (the mean age – 33.9 ± 9.09; F/M - 249/137) with postinfectious irritable bowel syndrome (IBS) were analyzed concerning lactase deficiency. All patients underwent intestinal endoscopy with biopsies from the mucosa of the descending duodenum in order to determine lactase deficiency. The biopsies were taken in order to determine lactase deficiency (normal, mild and severe) by means of lactose quick test (LQT). To diagnose small intestinal bacterial overgrowth (SIBO) all patients underwent lactulose breath test during 2 hours.

Results: SLD was detected in 36.5% of patients with postinfectious IBS. Mild SLD was determined in 25.6% of patients, and severe SLD – in 10.9% of patients. The specific clinical symptoms of mild SLD were moderate flatulence with abdominal pain (80.7%); the majority of patients (73.7 %) had normal stool consistency, one time a day; the other patients had semi-liquid faeces, 2-3 times a day (26.3%). The clinical symptoms of severe SLD were diarrhea (stool > 4 times a day) in 85.7% of patients, abdominal pain and flatulence (90.5%). SLD in all cases was accompanied by SIBO (the average level of lactulose breath test was 80.3 ± 28.3ppm, N < 20ppm). It turned out that the degree of lactase deficiency depends on the severity of SIBO in the lumen of the small intestine. Thus, when mild SLD average value SIBO was 72.4 ± 25.1ppm, whereas severe SLD average indicators of SIBO achieved higher values, 99.3 ± 26.9ppm (N < 20ppm). To establish the degree of dependence of SIBO in the small intestine and the degree of deficiency of lactase in the small intestine biopsies performed a statistical analysis of the results by calculating the Spearman rank correlation coefficient in order to study a statistically significant link between the various phenomena. In this study, an inverse correlation between the degree of lactase deficiency in patients with the SLD and the severity of SIBO in the small intestine, i.e. the higher the hydrogen concentration in the exhaled air, the less activity of the enzyme lactase in the small intestine biopsy specimens (r = -0.49, p <0.001).

Conclusion: SIBO in all cases was accompanied by SLD. Thus, the high frequency of the SLD associated with SIBO in the small intestine in patients postinfectious IBS can be explained by the growth of pathogenic microflora in the small intestine.

Disclosure of Interest: None declared

P1202 SMALL INTESTINAL BACTERIA OVERGROWTH AND USE OF PPI AS A PREDISPOSING FACTORS FOR NSAID-ENTEROPATHY

S. Tkach¹, L. Onischuk¹, A. Balabanceva²

¹Internal Medicine #1, National Medical University, Kyiv, Ukraine, ²Therapy@family medicine, Crimea Medical University, Simferopol, Russian Federation

Contact E-mail Address: tkachsergio@yahoo.com

Introduction: There is good evidence from animal studies that gut bacteria play an important role in the pathogenesis of NSAID-induced small bowel damage. Other studies demonstrated alterations in the composition of small bowel bacteria in human, often with increases in gram-negative bacteria, after the administration of NSAIDs. In a prospective study of chronic NSAID users, 50-60% were found to have severe small bowel damage by video capsule endoscopy, associated with small intestinal bacteria overgrowth (SIBO). There is ample evidence that proton pump inhibitors (PPIs) can induce alteration of intestinal flora and SIBO too.

Aims & Methods: Our aim was to evaluate the frequency of SIBO by using a hydrogen glucose breath test (H₂-GBT) and frequency of small bowel lesions in chronic PPIs (standard doses of omeprasole) and NSAIDs (diclofenac) users. We investigated 34 pts with NSAIDs-gastropathy (20 male, mean age – 45 years) with H₂-GBT (EC60 Gastrolyzer 2, Bedfont Scientific Ltd, Rochester, UK). All patients with positive results of H₂-GBT were examined with video capsule endoscopy (Given, Israel) and were treated with rifaximine (1200 mg/day during 10 days). The efficacy of treatment was controlled with repeated H₂-GBT.

Results: Overall, 20 pts (58.8%) had demonstrated positive results of H₂-GBT and presence of SIBO. Among this patients the small bowel lesions were found in 16 pts (80%) by using a video capsule endoscopy. After use of rifaximine (1200 mg/day during 10 days) negative H₂-GBT was found only in 2 (10%) patients with initially diagnosed SIBO.

Conclusion: High prevalence of SIBO in patients with NSAID- induced gastric damage treated with PPIs may confirm its important role in pathogenesis of NSAID-enteropathy. PPIs may exacerbate small bowel damage induced by NSAIDs through alteration of gut microbiota. Rifaximine is highly effective for treatment of SIBO.

Disclosure of Interest: None declared

P1203 SACCHAROMYCES BOULARDII STRAIN CNCM I-745 SHOWS PROTECTIVE EFFECTS AGAINST B. ANTHRACIS LT TOXIN

D. Czerucka¹, R. Pontier-Bres¹, P. Rampal², J.-F. Peyron¹, E. Lemichez¹

¹C3M, INSERM U1065, Nice, France, ²CSM, Monaco, Monaco

Introduction: Anthrax disease is a severe bacterial infection often characterized by both septicemia and toxemia. Toxemia depends on a tripartite toxin secretion. LT toxin, composed of the PA binding sub-units and LF catalytic unit, has been directly implicated in epithelia and endothelia barrier dysfunction observed in the gastrointestinal form of the disease. Massive reorganization of the actin cytoskeleton promoted by LT through MEK inhibition is a great system to study inhibitors of the intoxication process. The probiotic yeast Saccharomyces boulardii CNCM I-745 (S.b) is prescribed worldwide for prophylaxis and treatment of diarrheal diseases caused by bacteria, virus or antibiotics. Several studies have shown that S. b. exerts a proteolytic effect on several bacterial toxins while maintaining the barrier function of intestinal epithelium.

Aims & Methods

Aim: In this study we tested whether S.b might confer protective effect on cell intoxication by B. anthracis LT-toxin.

Material and Methods: The study was performed on filter grown polarized T84 cells or non-polarized HUVEC cells. Permeability was measured by trans-epithelial resistance (TER). The modifications in the distribution of the tight junctions associated protein ZO-1, and reorganization of actin cytoskeleton were monitored by confocal microscopy. MEK-2 cleavage, PA and LF degradation were detected by western-blot.

Results: After 15 and 24 hours incubation, LT toxin affected epithelial integrity which was visualized by a significant drop of TER in polarized T84 cells. In parallel we observed that LT toxin caused modification of tight junctions morphology with a diffuse staining of ZO-1. It induced as well formation of actin stress fibers in both cell lines. LT toxin is known to target mitogen-activated protein kinase kinases (MEK); kinetics studies on MEK-2 cleavage reveals in our study that it occurs at 2 hours of incubation in HUVEC cells and is delayed to 6 hours of incubation in T84 cells.

An overnight treatment with S. b before LT toxin incubation maintained the integrity of the monolayers, prevented morphological modification of tight junctions, restricted LT effects on actin remodeling and delayed LT-induced MEK -2 cleavage. Finally, to unravel the molecular mechanism by which S.b protects cells, the yeast was incubated with the LT subunits (PA and LF) for 2, 6, and 24 hours. After centrifugation, we determined that cleaved forms of PA were detected in the supernatant after 24 hours of incubation. A small quantity of PA and LF were also founded in the pellet containing S.b corresponding probably to yeast-bound toxins fraction. These results could explain the antitoxin activity of S. b.

Conclusion: Our study highlights the therapeutic potential of S.b strain CNCM I-745 to be used as prophylactic agent against the gastrointestinal form of B. anthracis infection.

Disclosure of Interest: D. Czerucka Financial support for research: Financial support for research by Biocodex, Conflict with: Salary paid by Biocodex, R. Pontier-Bres Financial support for research: Financial support for research by Biocodex, Conflict with: Salary paid by Biocodex, P. Rampal Consultancy: Consultant for Biocodex, J.-F. Peyron: None declared, E. Lemichez: None declared

P1204 EFFECT OF SACCHAROMYCES BOULARDII STRAIN CNCM I-745 ON DENDRITIC CELLS POPULATIONS IN THE LAMINA PROPRIA OF MICE FOLLOWING SALMONELLA TYPHIMURIUM INFECTION

D. Czerucka¹, R. Pontier-Bres¹, G. Michel¹, P. Rampal², J.-F. Peyron¹

¹C3M, INSERM U1065, Nice, France, ²CSM, Monaco, Monaco

Introduction: Recent studies characterized, in the lamina propria, two DCs populations that include: MHCII⁺CD11c^hiCD103⁺CD11b⁺(referred as CD103⁺CD11b⁺DCs) and MHC^hi CD11C^hiCD103⁻CD11b⁺(referred as CD103⁻CD11b⁺DCs). Buganovic M et al. (Immunity 2009) have previously established a difference of involvement of both populations of DC during infection of streptomycin-pretreated mice with Salmonella typhimurium (ST). The transport of pathogenic Salmonella from the intestinal tract to the mesenteric lymph nodes involves CD103⁺CD11b⁺DCs, whereas intracellular bacteria in the lamina propria reside in CD103⁻CD11b⁺ DCs. The probiotic yeast Saccharomyces boulardii CNCM I-745 (S.b) is prescribed worldwide for prophylaxis and treatment of diarrheal diseases caused by bacteria, virus or antibiotics. In the streptomycin-pretreated model, we demonstrated that S.b modifies ST propagation along the intestinal tract and ST translocation (Plos One 9 e103069).

Aims & Methods

Aim: Investigate the effect of S. b on the different DCs populations in the intestine of mice after Salmonella infection.

Material and Method: Bioluminescent imaging (BLI) was used to evaluate the effect of S.b on the progression of luminescent ST (ST-lux) in the GIT of mice pretreated with streptomycin. The intestine was sampled in three parts and the photon emission reflecting ST-lux progression was recorded in i) the site of maximum photon emission (“I°”), ii) the ileum, which showed no photon emission (“I⁻“), and iii) the duodenum, which had already been in contact with the bacteria (“I⁺”). The different DCs populations extracted from the Inflammatory cells were characterized by FACS. In vitro studies were performed on RAW264.7 cells exposed or not to S.b before infection. GM-CSF was detected in the supernatant by array.

Results: FACS analysis of DCs extracted from ST-lux alone infected mice revealed that the “I°” sample presented a population expressing CD103⁺CD11b⁺DCs and CD103⁻CD11b⁺DCs that was absent in the other part of the intestine: “I^−“ and “I^+”. The “I°” sample obtained from S.b pre-treated mice before infection presented a significantly reduced population expressing CD103⁺CD11⁺DCs and CD103⁻CD11b⁺ DCs when compared to “I°” portion of ST alone infected mice. Interestingly the “I^−“ portion of S.b treated mice (portion of intestine that has not been in contact with ST but has been in contact with yeast) contained a population expressing CD103⁻CD11b⁺ DCs. GM-CSF was required for the development of CD103 + CD11b + DCs. S.b abolished secretion of GM-CSF in RAW 264.7 infected by ST.

Conclusion: Altogether these data demonstrate that in vivo, shortly after ST administration, S.boulardii CNCM I-745 modulates the DCs composition of lamina propria by inducing the CD103⁻DCs and reducing the CD103⁺ DCs populations.

Disclosure of Interest: D. Czerucka Financial support for research: Financial support for research by Biocodex, Conflict with: Salary paid by Biocodex, R. Pontier-Bres Financial support for research: Financial support for research by Biocodex, Conflict with: Salary paid by Biocodex, G. Michel: None declared, P. Rampal Consultancy: Consultant for Biocodex, J.-F. Peyron: None declared

P1205 WHEN GASTRIC INHIBITION IMPLIES INTESTINAL BACTERIAL ALTERATION. A CONFIRMATION FROM A FOLLOW-UP STUDY

L. Lombardo¹, M. Schembri²

¹Gastroenterology Service, Poliambulatorio Statuto, ²Gastroenterology, Mauriziano Hospital, Turin, Italy

Contact E-mail Address: manuelaprinzio@yahoo.it

Introduction: The causative role of PPIs on small intestinal bacterial overgrowth (SIBO) is still controversial. However, the incidence of SIBO is increasing, probably because of the increase of pharmacological risk factors (1). Although SIBO can satisfactorily be eradicated by Rifaximin (2), its recurrence and retreatment are so far poorly investigated and may pose clinical challenges. Here we investigated the effect of PPIs, on a follow-up study, after the first successful eradication of SIBO by Rifaximin.

Aims & Methods: One hundred and forty four patients (pts) treated with long-term PPIs for gastro-esophageal reflux disease (GERD), successfully eradicated from SIBO with high dose Rifaximin were followed-up for 1 year for relapse investigation. A group of pts continued full dosage PPIs therapy (A group) while another stopped it (B group). An additional group of pts with IBS, eradicated from SIBO, not taking PPIs, was also followed-up, as control (C group). At the end of follow-up, or before if symptoms suggested it, glucose hydrogen breath test (GHBT) (Quintron, Milwaukee, WI, USA) was performed to each patient and symptoms were recorded. All relapsed pts were retreated with Rifaximin 1200 mg/die for 2 weeks, as in the first course. The outcome of therapy was assessed both clinically and by means of GHBT, 2 months after the completion of Rifaximin course.

Results: Out of a cohort of 144 pts (M 84; mean age 46 ± 14) successfully eradicated from SIBO with Rifaximin, 97 pts continued treatment with PPIs ( M 52, mean age 45 ± 13) and 47 (M 31, mean age 44± 14) discontinued it. An additional series of 20 pts with IBS (M11, mean age 43 ± 17), eradicated from SIBO, PPIs-free, were followed-up for 1 year. Forty-nine out of 97 pts of A group (50%), 3 out of forty-seven of B group (6%) and 1 out of 20 of C group (5%) had a SIBO relapse , with a statistically significant difference between the first group and the others (p < 0.001). Forty-seven out of 52 pts retreated with Rifaximin showed negative GHBT along-side symptoms remission (90%), indicating a successful eradication from SIBO. No relevant side effect was registered.

Conclusion: 1) Relapse rate of SIBO within 1 year is high if treatment with PPIs is not discontinued (90%). 2) Retreatment with Rifaximin 1200 mg/die for 2 weeks results to be effective and safe.

Disclosure of Interest: None declared

P1206 ABNORMAL DUODENAL PATHOLOGY IN SMALL INTESTINAL BACTERIAL OVERGROWTH AND FUNCTIONAL DYSPEPSIA

M. M. Walker¹, L. I. Wauters², B. Suliaman³, R. Warner¹, E. H. F. Bafutto⁴, M. P. Jones⁵, N. J. Talley⁶, M. Bafutto⁷

¹Anatomical Pathology, University of Newcastle, Newcastle, Australia, ²Translational Research Centre for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium, ³Anatomical Pathology, Pathology North Hunter, Newcastle, Australia, ⁴Institute of Gastroenterology, Faculdades Integradas da União Educacional do Planalto Central , Brasília, Brazil, ⁵Psychology Department , Macquarie University, Sydney, ⁶University of Newcastle, Newcastle, Australia, ⁷Institute of Gastroenterology, Universidade Federal de Goiás, Goiânia, Brazil

Contact E-mail Address: marjorie.walker@newcastle.edu.au

Introduction: Small intestinal bacterial overgrowth (SIBO) is characterized by a variety of clinical features thought to result from alteration of the microbiota within the upper gastrointestinal (GI) tract and commonly defined as the presence of > 10⁵ colony forming units/ml of bacteria in an aspirate of fluid collected from the upper small intestine¹. SIBO can be diagnosed with the lactulose H2 breath test, which is a non-invasive, low cost, simple test². Symptoms related to SIBO are heterogeneous and may mimic functional GI disorders, including functional dyspepsia (FD).

Aims & Methods: This study aimed to define whether abnormal duodenal pathology previously related to dyspeptic symptoms (increased duodenal eosinophilia) occurs in patients with dyspepsia and SIBO.

This was a prospective case-control study, 9 patients with normal upper endoscopy, upper abdominal ultrasonography, and symptoms of functional dyspepsia (FD; 8 females, mean age 37 years, range 19-63,) were compared to 9 patients with SIBO (defined by lactulose H2 breath test) and functional dyspepsia (7 females, mean age 46 years, range 31-72). Biopsies were taken from the gastric antrum and duodenum, and examined for routine pathologies by haematoxylin and eosin staining, plus additionally eosinophil counts/ mm² and mast cells by immunocytochemistry (CD117). Symptoms of FD and the presence of postprandial distress syndrome (PDS), and epigastric pain syndrome (EPS) were recorded. Effect sizes are reported as Cohen’s d (>0.5 moderate, >0.8 is large effect size) and comparisons between SIBO and non-SIBO FD was undertaken using the Mann-Whitney test for immune cell counts and Chi-Square for categorical measures.

Results: All patients were non-smokers, with no allergies and no parasitic ova on stool microscopy. SIBO patients were more likely to have postprandial distress symptoms (PDS) (77% v 44%, p =  0.1) or PDS alone (33% v 11%, p = 0.3). SIBO patients showed evidence of reduced duodenal eosinophils (d=-0.76, p = 0.08), elevated duodenal intraepithelial lymphocytes (d=+0.50, p = 0.3) and reduced duodenal mast cells (d=-0.57, p = 0.5) compared to those with FD alone. Failure to reach statistical significance despite moderate to large effect sizes is likely due to low sample size with statistical power 0.3 or less for all comparisons. In contrast there was minimal evidence of difference between SIBO and non-SIBO FD patients with respect to gastric eosinophils (d=-0.14, p > 0.9) or gastric intraepithelial lymphocytes (d=-0.37, p = 0.7).

Conclusion: SIBO in patients with functional dyspepsia appears to be associated with alteration in duodenal but not gastric innate immune response and may be associated with the PDS rather than EPS FD subtype. Larger studies are required to improve the statistical certainty of these findings.

Disclosure of Interest: None declared

P1207 SMALL INTESTINAL BACTERIAL OVERGROWTH MAY INCREASE THE LIKELIHOOD OF LACTOSE, FRUCTOSE AND SORBITOL INTOLERANCE FALSE POSITIVE DIAGNOSIS

T. T. Perets¹, D. Hamouda¹, E. Shporn¹, Y. Niv², R. Dickman²

¹Gastroenterology Laboratory, ²Gastroenterology Department, Rabin Medical Center - Beilinson Hospital, Petah Tikva, Israel

Contact E-mail Address: kaiser1974@gmail.com

Introduction: Small intestinal bacterial overgrowth (SIBO) is defined by the presence of an excessive concentration of bacteria in the small intestine. Lactose intolerance (LI), fructose intolerance (FI) and sorbitol intolerance (SI) and SIBO share many gastro-intestinal (GI) symptoms usually attributed to patients diagnosed with irritable bowel syndrome (IBS).

Aims & Methods: To evaluate the role and effect of SIBO in the formation of LI, FI and SI symptoms in affected patients. A total of 348 patients with suspected IBS underwent SIBO and LI, FI and SI diagnosis by hydrogen breath test (HBT). 15 gr of lactulose dissolved in 50 ml of water and 50 gr of lactose, 25 grams of fructose and 15 grams of sorbitol dissolved in 250 ml of water were used for SIBO and LI, FI and SI HBT respectively. The test results were considered positive when hydrogen concentration acceded 10 PPM for SIBO and 20 PPM for LI, FI or SI above baseline.

Results: Out of the 348 patients tested for SIBO and LI, 101 (29%) were positive for both tests. Out of the 197 patients tested for SIBO and FI, 17 were positive for both tests. And finally, out of the 196 patients tested for SIBO and SI, 45 were positive for both tests. Out of the 101 SIBO and LI, 17 SIBO and FI and 45 SIBO and SI positive patients, 82 (81%), 14 (82%) and 23 (53%) respectively had an increase of hydrogen measurement above threshold between 30-90 minutes during their LI/FI/SI-HBT, implying SIBO.

Conclusion: The fermentation of lactose, fructose or sorbitol in the small bowel due to SIBO may increase the likelihood of LI, FI and SI incorrect diagnosis. We suggest that all symptomatic patients will undergo SIBO testing and eradication if diagnosed positive, prior to LI, FI or SI HBT evaluation.

Disclosure of Interest: None declared

P1208 A PROSPECTIVE APPLICATION OF THE ESPGHAN GUIDELINES IN A SYMPTOMATIC ADULT POPULATION

K. Efthymakis¹, M. Serio¹, D. D'Amato¹, A. Milano¹, F. Laterza¹, A. Bonitatibus¹, M. Neri¹

¹Medicine and Ageing Sciences and CESI, Università "G. D’Annunzio", Chieti, Italy

Contact E-mail Address: efkn78@gmail.com

Introduction: Current adult guidelines require histological confirmation of celiac disease (CD)[1]. However, recent pediatric guidelines have proposed algorithms to reduce the need for biopsy in genetically susceptible symptomatic children[2].

Aims & Methods: To explore the applicability of the current ESPGHAN criteria and assess the accuracy of serology in detecting mucosal abnormalities in a prospective cohort of symptomatic adults. We recruited 234 consecutive symptomatic adults (mean age=33.9ys) referred to our tertiary center, showing EMA positivity and genetic susceptibility. All patients underwent upper endoscopy with multiple biopsy sampling in the duodenum. Histological lesions were graded according to the Corazza-Villanacci classification and considered diagnostic for grades ≥ B. Anti-tTG titers were assessed with 12 different assays; one ELISA kit (specified Upper Limit of Normal=3.5U/ml) was used in 141 subjects (60.3%), while a second one in 59 (25.2%, ULN ± 9.9U/ml). Accuracy of anti-tTG testing and optimal cut-off levels were determined by means of a ROC curve. Performance was also calculated for a cut-off 10 times ULN.

Results: Mean anti-tTG levels at inclusion were 71.1 ± 4.4U/ml, while mean adjusted levels (anti-tTG/ULN) were 14.8 ± 0.9 times ULN (mean ± SE). Among the 234 patients, 21 (9%) showed no atrophy; partial and total atrophy were present in 85 (36.3%) and 128 (54.7%) respectively. Anti-tTG levels significantly correlated to the degree of villous atrophy (ANOVA p<0.001; ρ_s=0.397, p<0.001). AUC proved a fair diagnostic accuracy both for the unadjusted and adjusted anti-tTG levels (respectively 0.803, 0.807; p<0.01). For the ESPGHAN criterion of anti-tTG ≥ 10 times ULN, a positive predictive value (PPV) of 97.7% was calculated (sensitivity=59.2%, specificity=86.9%). The optimal cut-off for adjusted anti-tTG levels was ≥16 times ULN, with a PPV of 98.9% (sensitivity=41.2%, specificity=95.7%). Considering different assays, results were puzzling; although in the first one PPV(=97.14%) seemed to peak at around 50U/ml (14.3 times ULN), the second assay proved considerably more predictive: for a cut-off=37.3U/ml (3.7 times ULN) it showed a superior PPV=100% (sensitivity 53.1%, specificity 100%). Age and sex did not correlate with histology or serology.

Conclusion: In an adult population of symptomatic patients showing EMA positivity and genetic susceptibility, anti-tTG titers correlate with the degree of villous atrophy. The ESPGHAN criteria showed a PPV similar to that of symptomatic children[3]. However, PPV was higher for a cut-off 16 times ULN and peaked when considering a single ELISA assay, indicating a possible kit-specific variability. Further studies are required to determine if optimal cut-off levels are dependent on patient or assay characteristics. The findings of this study could prove useful when assessing equivocal histological cases of CD, and could help in guiding patient follow-up.

Disclosure of Interest: None declared

P1209 THE DIAGNOSTIC DELAY IN CELIAC DISEASE IS SIGNIFICANTLY INCREASED IN WOMEN DUE TO DOCTOR’S BUT NOT PATIENT’S DELAY

S. Vavricka¹, A. Schoepfer², P. Frei³, G. Rogler⁴, L. Biedermann⁴

¹Gastroenterology & Hepatology, Hospital Triemli, Zurich, ²Gastroenterology & Hepatology, Centre Hospitalier Universitaire Vaudois/CHUV, Lausanne, ³Gastroenterology & Hepatology, Clinic Bethanien, ⁴Gastroenterology & Hepatology, University Hospital Zurich, Zurich, Switzerland

Contact E-mail Address: luc.biedermann@usz.ch

Introduction: The majority of celiac disease (CD) cases are associated with a considerable diagnostic delay or even remain undiagnosed due to a variety of reasons, such as silent disease, unspecific symptoms with overlap to other diseases and insufficient awareness in both patients as well as physicians. The total diagnostic delay can be subdivided into patient’s (gap between beginning of symptoms and first medical consultation) and doctor’s (gap between first medical consultation and definitive diagnosis of CD) delay. There is insufficient data on diagnostic delay, its comprising two components and associated factors in CD. In addition, it remains to be clarified, whether its extent has an impact on the course of the disease.

Aims & Methods: We performed a large systematic, nation-wide patient survey study among unselected CD patients in Switzerland.

Results: A total of 1689 patients (76% female; mean age 41.3 y, range 0-92y, mean age at diagnosis 31.1y, range 0-83y) were analysed. We found a mean total diagnostic delay of 72.3 months (median 18, IQR 4-72), with an enormous range from 0 up to 780 months and roughly equal fractions of patient’s and doctor’s delay with a mean/median of 39.9/4 (IQR 0-28) and 39.4/3 (IQR 0-24) months, respectively. While the mean age of diagnosis was not different in female vs. male patients (31.2 vs. 31 years), both, mean/median total (76.2/21 vs. 56.9/12, p = 0.008) and doctor’s (43.8/5 vs. 25.6/2, p < 0.001) diagnostic delay was significantly higher in female vs. male patients, whereas patient’s delay was similar (39.4/3 vs. 37.8/2, not significant).

A total of 15.3% of patients reported that IBS was diagnosed or suspected by their treating physician(s), prior to establishing the diagnosis of, significantly more women than men (16.7 vs. 10.5%, p = 0.004). Notably, a significantly higher doctor’s delay in women was equally observed if patients with antecedent IBS diagnoses were excluded (mean/median total, patient’s and doctor’s delay of 67.1/16 vs. 45.5/11, p = 0.015; 37.8/3 vs. 33/2, n.s.; 36/4 vs. 22.5/2, p = 0.004 in non-IBS women vs. men).

Treatment of any nutritional deficiencies states was significantly more often required in patients with a delay ≥24 vs. <24 months (74.6 vs. 58.4%, p < 0.001). The same was observed for need of steroids and/or immunosuppressants to treat CD with 4.4 vs. 2.0%, corresponding to a relative risk of 0.48 (CI 0.26-0.87, p = 0.016).

In addition, total, patient’s and doctor’s diagnostic delay was significantly higher in patients diagnosed after vs. up to the age of 30 (mean/median 106.3/32, 59.5/4 and 58.5/6 vs. 35.7/12, 18.9/2 and 19.3/3 months, respectively, for all p < 0.001).

Conclusion: There is a substantial diagnostic delay in CD, which is significantly longer in patients with older age at diagnosis and in female patients. The increased diagnostic delay in women is due to doctor’s but not patient’s delay. This increase in doctor’s delay cannot be explained by antecedent symptoms or diagnosis of IBS prior to establishing the diagnosis of CD. Our findings point to an insufficient awareness for CD in physicians especially in women and older patients. In addition, a longer diagnostic delay is associated with more frequent need of immonusuppressants to treat CD and a lower chance of clinical remission after diagnosis.

Disclosure of Interest: None declared

P1210 THE SELECTED PARAMETERS OF OXIDATIVE STRESS, ANTIOXIDANT CAPACITY AND INFLAMMATORY MEDIATORS IN TREATED AND UNTREATED ADULT PATIENTS WITH COELIAC DISEASE - A PRELIMINARY REPORT

M. Zwolinska-Wcislo¹, A. Piątek-Guziewicz¹, P. Paśko², P. Zagrodzki², M. Krośniak², M. Przybylska-Feluś¹, A. Ptak-Belowska³, T. Mach¹

¹Gastroenterology, ²Department of Food Chemistry and Nutrition, ³Department of Physiology, Jagiellonian University Collegium Medicum, Krakow, Poland

Contact E-mail Address: mzwcislo@su.krakow.pl

Introduction: It has been assumed that oxidative stress is one of the mechanism that can play a role in gluten toxicity although its role in patients with celiac disease (CD) is not fully elucidated.

Aims & Methods: To evaluate the cytotoxic effect of gluten by determining the selected parameters of oxidative stress, antioxidant capacity and inflammatory mediators in treated and untreated adult patients with CD The study has enrolled 98 patients, including 72 patients with CD. The subjects were divided into 3 groups: 1) patients with untreated CD (N = 35), including patients with newly diagnosed CD (N = 10) and patients not adhering to a gluten-free diet (GFD) (N = 25), 2) patients with CD on GFD for at least two years (n = 37), 3) healthy control group (N = 26). A standard blood test, the level of anti-tissue transglutaminase antibodies and /or endomysial antibodies and histopathological study of duodenal biopsy were evaluated. The serum concentration of nitric oxide (NOx), IL-15, FRAP (Ferric Reducing Antioxidant Power), reduced glutathione (GSH) and glutathione peroxidase (GPx) were detected.

Results: There were no differences between the groups in serum concentrations of Il-15. The concentration of GSH in untreated patients was lower than in patients on GFD and control group. GPx activity was lower in treated and untreated CD group than in controls. FRAP level was reduced in patients with CD compared to the controls. The serum level of nitrate in patients with CD without GFD were significantly higher than those of controls (p < 0.001). Patients who were on a gluten-containing diet had also significantly lower values of RBC, HGB and HCT in comparison to control group. Patients who did not obey GFD had significantly higher serum level of nitrate and the level of coeliac antibodies (p < 0.001) and lower level of MCV in comparison to the patients who used recommended diet. It was observed that ferritin concentration was positively correlated with iron concentration (CW=0.402), AST (CW=0.542), bilirubin (CW=0.501), and with GGTP (CW=0.824). The latter parameter was also correlated with AST (CW=0.551), bilirubin (CW=0.493) and with total cholesterol level (0.417). Two parameters, nitrate level and ALT were also highly positively correlated (CW=0.503).

Conclusion: Oxidative/antioxidative balance is shifted toward oxidative side by gluten-containing diet in patients with CD. GFD, especially enriched in antioxidants may decrease oxidative stress in this group. Results of study suggested the role of serum NO as an indicator of diet compliance. Strong correlation between NO level and ALT may suggest the role of NO in the pathogenesis of gluten-induced hepatitis. Further research are needed.

Disclosure of Interest: None declared

P1211 GLUTEN-FREE DIET DOES NOT INFLUENCE THE OCCURRENCE AND THE TH1/TH2 NATURE OF IMMUNE-MEDIATED DISORDERS ASSOCIATED WITH COELIAC DISEASE

N. Imperatore¹, A. Rispo¹, P. Capone¹, G. D. De Palma², N. Gerbino¹, M. Diaferia¹, N. Caporaso¹, R. Tortora¹

¹Gastroenterology - Department of Clinical Medicine and Surgery, ²Surgery - Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy

Contact E-mail Address: nicola.imperatore@alice.it

Introduction: Even though coeliac disease (CD) is considered to be the most common lymphocyte T helper-1 (Th-1) mediated enteropathy in Western countries, it seems that Th1- and lymphocyte T helper-2 (Th-2 )-mediated diseases could co-exist in CD patients.

Aims & Methods: The aims of the study were: 1) to establish the prevalence of immune-mediated disorders at time and after CD diagnosis; 2) to evaluate a possible change in immune response after starting gluten-free diet (GFD); 3) to investigate the potential role of GFD in reducing and/or preventing immune-mediated disorders in adult CD patients.

Methods: We carried out a database-driven study including all consecutive adult CD patients followed-up at our Gastrointestinal Unit. CD diagnosis was made in accordance with the Oslo classification. The main demographic, clinical, serological, endoscopic and histological features were recorded for all CD patients. All patients were investigated for the presence of Th1 and/or Th2-mediated disorders at time of CD diagnosis. The search for Th1 and/or Th2 diseases were reassessed after a 5-years follow-up period. Statistical analysis included chi-square (χ²) test, Mann-Whitney U test, ANOVA and odds ratio (OR) when indicated. All results were considered significant with a p< 0.05.

Results: Finally, 1255 CD were enrolled (M/F 258/997). 257 patients out of 1255 (20.5%) suffered from immune-mediated diseases at time of CD diagnosis, with 150 of them (58.4%) presenting a Th1-predominant disease vs 107 (41.6%) with Th2-mediated diseases (p = 0.7). After a 5-years follow-up period, 682 out of 1255 patients (54.3%) showed an immune-mediated disease even if following a restrict GFD; among them, 391 subjects (57.3%) presented a Th1-related condition vs 291 (42.7%) with a Th2-mediated disease (p = 0.8). When comparing the prevalence of immune-mediated diseases before and after CD diagnosis, no significant “switch” from Th1- to Th2-response or vice versa was seen (58.4% and 41.6% before CD vs 57.3% and 42.7% after CD diagnosis, respectively; p = ns). The number of patients with a Th1- and/or a Th2-merdiated disease increased during the GFD period (20.5% vs 54.3%; p < 0.01; OR 1.9). The most frequent CD-related immune-mediated diseases were: Hashimoto’s thyroiditis (8.2% before vs 24% after CD diagnosis; p < 0.01; OR 1.6); psoriasis (0.7% before and 2.7% after CD diagnosis; p < 0.01; OR 1.5), type 1 diabetes mellitus (1.8% before vs 0.2% after CD diagnosis; p < 0.01; OR 0.08). No correlation was found between the developed immune-mediated diseases and age at the time of CD diagnosis, clinical symptoms, a-tTG serum levels and Marsh grade.

Conclusion: The prevalence of immune-mediated diseases at time of CD diagnosis, particularly as regards with Hashimoto’s thyroiditis, psoriasis and type 1 diabetes mellitus, is high and it seems to increase in the follow-up period despite GFD. GFD does not influence and/or reduce the prevalence, the occurrence and the Th1/Th2 nature of immune-mediated diseases in CD.

Disclosure of Interest: None declared

P1212 THE PREVALENCE OF COELIAC DISEASE AT THE INTERSECTION OF EUROPE AND ASIA: A POPULATION-BASED CROSS-SECTIONAL STUDY FROM MERSIN, TURKEY

O. Sezgin¹, B. Sarıtaş², I. Aydın³, T. Şaşmaz⁴, E. Serinsöz Linke⁵

¹Gastroenterology, ²Mersin University School of Medicine, ³70. Yıl Family Health Center, ⁴Public Health, ⁵Pathology, Mersin University School of Medicine, Mersin, Turkey

Contact E-mail Address: drorhansezgin@gmail.com

Introduction: Coeliac Disease (CD) has emerged as a public health problem, and the disease prevalence varies among different races and nations. In Turkey, which stands at an important transition point at the junction of Europe and Asia where the races mix, an adult community-based prevalence study has not been conducted as yet. Thus, the present study was designed to investigate the prevalence of undiagnosed CD in Turkish adult population in Mersin and to detect the characteristics of these pts.

Aims & Methods: This study was undertaken during the June 2011–January 2013. Mersin is a cosmopolitan city in the South of Turkey, which has 10 different districts. Adults aged 18 and older living within the Mersin formed the target population of the study. According to 2009 population census results, there are 1133935 people in this age group living in Mersin. The minimum sample size has been calculated as 1519. It was planned to include 1600 people in the study group. The study group was sorted based on age, gender and district via stratified sampling method. Family physicians were selected district-wide through random sampling method. Respondents to be sampled were chosen from those registered to each family physician by using stratified sampling method. Participants were evaluated for demographic features, and gastrointestinal symptoms, and were tested for anti-tissue transglutaminase (tTG) and anti-Deaminated Gliadin Peptid (DGP) immunoglobulin (Ig) A and IgG using an ELISA assay. Small intestinal biopsies were obtained from the seropositive pts, and they were examined according to the Marsh classification. HLA-DQ2 and DQ8 genotyping and blood tests were done.

Results: 1554 people participated in this study and the participation rate was 97.1%. The mean age was 42 years and 50.4% were female. 12 of the participants showed anti-tTG/DGP IgA or IgG positivity. Thus, the total seropositivity was 0.77%. The mean age of seropositive participants was 41 years, and 83% of them were female. All seropositive participants were either HLA-DQ2 or DQ8 positive. 5 pts had Marsh type 3 pathology, 1 had Marsh type 2. The other 6 pts had Marsh type 0. Endoscopic findings concordant with celiac disease observed in only 5 pts with Marsh type 3 pathology. All pts were asymptomatic; but 5 pts had iron deficiency anemia, 1 had deficiency of vitamin B12 and premenopausal osteoporosis and her daughter was diagnosed with CD earlier. One had the IgA deficiency. 1 pt had been diagnosed Hashimato tiroiditis before. The niece of 1 pt was diagnosed with CD. The son of a male pt, who had diagnosis of irritabl bowel syndrome earlier, was diagnosed with CD after reevaluation.

Conclusion: This study is the first population-based prevalence study of CD in Turkish adults. We found that seroprevelance of CD is 0.77%. All pts were asymptomatic. Iron deficiency anemia was the most common finding and positive family history stood out. The importance of serology for diagnosis should not be disregarded and it should be kept in mind that histologic and endoscopic findings were negative in half of the cases.

Disclosure of Interest: None declared

P1213 INNATE AND ADAPTIVE CYTOKINES AND CHEMOKINES IN THE DUODENAL MUCOSA OF SUBJECTS WITH NONCELIAC GLUTEN SENSITIVITY VERSUS CELIAC DISEASE

P. Giuffrida¹, C. Salvatore¹, A. Vanoli², D. Bagordo¹, G. R. Corazza¹, A. Di Sabatino¹

¹First Department of Medicine, ²Department of Molecular Medicine, St Matteo Hospital, University of Pavia, Pavia, Italy

Contact E-mail Address: paolo.giuffrida01@gmail.com

Introduction: Immune mechanisms have been implicated in the pathogenesis of nonceliac gluten sensitivity (NCGS), a condition characterized by intestinal and/or extraintestinal symptoms caused by the ingestion of gluten in nonceliac/non-wheat allergic individuals.

Aims & Methods: We here investigated both innate and adaptive cytokines and chemokines in the duodenal mucosa of subjects with NCGS. Duodenal biopsies from 14 NCGS subjects, nine patients with untreated celiac disease (CD) and 12 control individuals were cultured ex vivo for 24h, and in the culture supernatants we detected by ELISA interleukin (IL)-15, and by cytokine array a number of innate cytokines, including tumor necrosis factor-a, IL-1b, IL-6, IL-12p70, IL-23, IL-27 and IL-32a, adaptive cytokines, including interferon (IFN)-g, IL-17A, IL-4, IL-5, IL-10 and IL-13, chemokines, including CCL1, CCL2, CCL3, CCL4, CCL5 and CXCL1, and growth factors, including granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF). Eleven out of 14 NCGS subjects underwent a double-blind, placebo-controlled crossover trial, over which their intestinal and extraintestinal symptoms were scored.

Results: Both innate and adaptive cytokines, chemokines and growth factors did not differ between NCGS subjects and control individuals. On the contrary, mucosal levels of IL-6, IL-15, IL-27, IFN-g, IL-17A, IL-23, G-CSF, GM-CSF, CCL1 and CCL4 were significantly higher in patients with untreated CD in comparison to NCGS subjects and control individuals. No statistical significant correlation was found between innate/adaptive cytokines, chemokines or growth factors and clinical response to gluten or placebo.

Conclusion: Abnormalities of the mucosal immune response in terms of either innate/adaptive cytokines or chemokines do not seem to be implicated in the pathogenesis of NCGS.

Disclosure of Interest: None declared

P1214 A CROSS-SECTIONAL STUDY OF THE CLINICAL PHENOTYPE IN COELIAC DISEASE IN A LARGE COHORT OF IRISH PATIENTS

P. Dominguez Castro¹, C. Kiat², J. L. Chin¹, G. Harkin², V. Trimble¹, T. Martin³, D. Kevans¹, P. MacMathuna³, N. Mahmud¹, V. Byrnes², N. Kennedy¹, R. McManus¹

¹Institute of Molecular Medicine & Department of Clinical Medicine, Trinity College Dublin, Dublin, ²Department of Clinical Medicine, University College Hospital Galway, Galway, ³Gastrointestinal Unit, Mater Misericordiae University Hospital, Dublin, Ireland

Contact E-mail Address: domingup@tcd.ie

Introduction: Coeliac disease (CD) occurs both in adults and children at a rate of approximately 1% in most populations ⁽¹⁾. There has been a considerable increase in CD positive serology over time. CD has a wide spectrum in its clinical presentation ^(1-4). The co-existence of CD with other disorders has been well reported ^{(5, 6)}. Few studies have addressed the clinical phenotype of CD in Ireland, and those available consist of small samples with little information on associated disorders ^(7-9).

Aims & Methods: The aim of this study is to explore the clinical phenotype of a large cohort (n=443) of Irish CD patients (310 females, median age 57 years, range 16-87 years) through the retrospective analysis of medical charts.

Results: The median age of diagnosis was 45 years (range 0.5-86 years). Onset of CD was symptomatic in 383 patients (93%), while 29 presented with a subclinical phenotype (7%). 305 (68.8%) patients reported having ever suffered from common disorders associated with CD (i.e. osteoporosis, iron deficiency, depression). These patients were diagnosed later in life (Median=48 years) than those who did not report having had any of these conditions (Median=39 years) (p = 0.001). 145 patients (32.7%) had a coexistent autoimmune disorder, the most prevalent being thyroid disease (19.6%).

Conclusion: CD patients commonly present with other autoimmune and non-autoimmune conditions. Diagnosis later in life appears to be associated to the development of co-existent non-autoimmune disorders.

Disclosure of Interest: None declared

P1215 PREDICTING HISTOLOGICAL REMISSION IN PATIENTS WITH CELIAC DISEASE ON A GLUTEN-FREE DIET

P. D. Mooney¹, M. Kurien¹, M. Burden¹, S. Wong¹, D. S. Sanders¹

¹Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, United Kingdom

Contact E-mail Address: p_d_mooney@hotmail.com

Introduction: Up to 30% of patients with celiac disease (CD) will have persistent symptoms despite the introduction of a gluten-free diet (GFD). Assessment of adherence in celiac disease can involve any combination of patient self-reporting adherence, dietetic assessment, serology and biopsy with histology. Histology is considered to be the ‘gold standard’ but this requires a repeat endoscopic examination with its associated risks and problems with tolerance. As a result surrogate markers of persistent gluten exposure and histological changes such as serology are frequently used but the relationship between serology and persistent histological changes is not linear. A structured interview with a dietician has been shown to be the most accurate method of assessing GFD adherence however this is time consuming and requires extra clinic visits. The aim of this study was to assess the usefulness of two novel options. Firstly a previously internally validated scoring system for assessing GFD adherence¹ (which has never been externally validated) and secondly a rapid deamidated gliadin peptide based point of care test (POCT, Simtomax) for the prediction of persistent villous atrophy (VA).

Aims & Methods: All patients with known CD and persistent symptoms coming to a specialist CD endoscopy list for the re-assessment of histology were invited to take part. All patients were tested for Endomysial Antibody (EMA), tissue transglutaminase (tTG), immunoglobulins and the POCT. They were also asked to complete a questionnaire to calculate a 5 point score (0 – 4) with a high score representative of improved adherence to a gluten-free diet. All patients underwent gastroscopy with at least 4 biopsies from the second part of the duodenum and 1 to 2 biopsies from the bulb.

Results: 94 patients (77% female, mean age 52.6) were recruited between April 2013 and December 2014. Median duration of GFD was 84 months (range 6-768). 36 (38.3%) patients had persistent VA on duodenal biopsy. The POCT was the most sensitive marker with 63.4% of patients with VA having a positive test. EMA was the most specific surrogate marker at 82.8% although it was highly insensitive with only 33.0% of patients with VA having a positive EMA. The adherence score could not be reliably used to predict VA with a sensitivity of only 30.6%.

Measure	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)
Adherence Score	30.6	79.3	47.8	64.8
tTG	50.0	75.9	56.3	37.9
EMA	33.0	82.8	54.5	66.7
POCT	63.4	60.3	50.0	72.9

Conclusion: An accurate surrogate marker for VA could reduce the number of endoscopies required. In this cohort the POCT had the best sensitivity, detecting 23/36 (63.4%) cases of villous atrophy, however this is pilot data and further work is required. It may be that additive methods for assessing adherence could achieve 100% sensitivity.

Disclosure of Interest: P. Mooney: None declared, M. Kurien: None declared, M. Burden: None declared, S. Wong: None declared, D. Sanders Financial support for research: Grants from Tillotts Pharma and BHR pharmaceuticals for investigator led studies into coeliac disease

P1216 HEART RATE VARIABILITY (HRV) – PREDICTOR OF MESENTERIC ISCHEMIA IN CARDIAC PATIENTS

A. I. Suceveanu¹, A. P. Suceveanu¹, F. Voinea¹, I. R. Parepa², D. Catrinoiu³, L. Mazilu³

¹Gastroenterology, ²Cardiology, ³Internal Medicine, St Apostle Andrew Emergency Hospital, Constanta, Romania

Contact E-mail Address: andrasuceveanu@yahoo.com

Introduction: Reduced HRV is proved to be a predictor of mortality after myocardial infarction and other medical conditions, including congestive heart failure, diabetic neuropathy, depression or post-cardiac transplant status. Mesenteric ischemia (MI) is a medical condition in which inflammation and injury of the small intestine result from inadequate blood supply.

Aims & Methods: We aimed to identify if the decrease-frequency component of HRV may be used as a predictor for the mesenteric ischemia (MI) occurrence in cardiac patients before the onset of digestive symptoms. Using ECG recordings, we measured the HRV in 170 patients admitted in Cardiac Care Unit (CCU) of St. Apostle Andrew Emergency Hospital of Constanta County. The study was done in collaboration with Gastroenterology Department of the same medical institute. We created a model of prediction for occurrence of MI in patients with cardiac diseases using correlations between the type of HRV and MI.

Results: From the total of 170 patients hospitalized in CCU in 3 months (January - March’ 15), 24 (14.11%) patients developed MI. From the total of 36 patients with decreased high-frequency HRV, 18 patients (50%) developed the MI. In contrast, only 6 patients (4%) of those with high-frequency value of HRV get the disease. Our results fixed a positive correlation between reduced high-frequency of HRV and MI occurrence (r=0.98).

Conclusion: Identifying the HRV in cardiac patients and making interventions to improve the parasympathetic nervous system activity we can simply avoid the occurrence of a high risk mortality disease that can worsen the prognosis of cardiac patients.

Disclosure of Interest: None declared

P1217 SUPERIOR MESENTERIC ARTERY SYNDROME: CLINICAL, ENDOSCOPIC AND RADIOLOGICAL FINDINGS

E. Sinagra¹², S. Testai³, M. marasà³, M. Blasco⁴, V. Alaimo⁵, D. Sorrentino⁵, V. Mastrella⁵, D. Albano⁶, G. Albano⁵, G. C. Morreale⁷, G. Amvrosiadis⁷, M. Midiri⁸, D. Raimondo²

¹Section of Nutrition, IEMEST, Palermo, ²Endoscopy and Gastroenterology Unit, Fondazione Istituto San Raffaele - G. Giglio di Cefalù, Cefalù, ³DIBIMEF, University of Palermo, Radiology Unit, Palermo, ⁴Internal Medicine Unit, Fondazione Istituto San Raffaele - G. Giglio, ⁵Radiology Unit, fondazione Istituto San Raffaele - G. Giglio di Cefalù, Cefalù, ⁶Radiology Unit, DIBIMEF, Univerity of Palermo, ⁷Endoscopy and Gastroenterology Unit, Ospedale V. Cervello, Palermo, ⁸Radiology Unit, Fondazione Istituto San Raffaele - G. Giglio, Cefalù, Italy

Contact E-mail Address: emanuelesinagra83@googlemail.com

Introduction: The superior mesenteric artery (SMA) syndrome is a rare entity presenting with upper gastrointestinal tract obstruction and weight loss, due to the compression of the third part of duodenum between the aorta and the SMA. Studies to determine the optimal methods of diagnosis and treatment are essential.

Aims & Methods: This study aims to analyze the clinical presentation, the diagnosis and the management of SMA syndrome. Over a 2-year period (2013-2014), 10 cases of SMA syndrome (out of 2074 esophagogastroduodenoscopies (EGDS)) were initially suspected through EGDS. Therefore, these patients performed computed tomography (CT) scan to confirm the diagnosis. Once the diagnosis was confirmed, the patients were referred to a gastroenterologist and to a nutritionist to discuss a personalized approach of therapy; furthermore, for each patient a surgical consultation was proposed.

Results: In our series we evaluated retrospectively 10 cases of SMA (8 females), with a prevalence of 0.005%. Median age was 23.5 years (range 14-40), and the median body mass index was 21.5 kilos/m2. Symptoms developed between 6 to 24 months (median 18). Premorbid conditions were present in four patients (Anorexia nervosa in two patients, and Spina bifida and Crohn's disease in two patients). Only 2 of 10 patients were hospitalized, due to severe malnutrition. Median aorto-mesenteric angle was 22°, and median aorta-SMA distance was 6 mm. Interestingly, all the patients improved on conservative treatment.

Conclusion: o date, SMA syndrome represents a diagnostic and therapeutic challenge. With regard to previous series published, our results show: the importance of the endoscopic suspicion of SMA syndrome, confirmed by CT scan; the preponderance of a longstanding and chronic onset; a female preponderance; the importance of the nutritional counseling in the therapeutic approach; the absence of need for surgical intervention; the better diagnostic accuracy of the narrowing of the aorta-SMA distance, rather than the narrowing of the aortomesenteric angle. Further prospective studies, with a larger number of patients, are needed to clarify the best way to diagnose and manage the SMA syndrome.

Disclosure of Interest: None declared

P1218 HIGH VARIATION IN TREATMENT STRATEGIES FOR GASTROINTESTINAL ANGIODYSPLASIAS: A NATIONWIDE SURVEY IN THE NETHERLANDS

K. Grooteman¹, E. van Geenen¹, J. Drenth¹

¹Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, Netherlands

Contact E-mail Address: karina.grooteman@radboudumc.nl

Introduction: Gastrointestinal angiodysplasias are the second leading cause of gastrointestinal bleeding in the elderly. On the other hand, angiodysplasias can be a coincidental finding on endoscopy and asymptomatic. Guidelines assisting in a treatment strategy in patients with symptomatic angiodysplasias are lacking.

Aims & Methods: Our aim was to assess current practice of the treatment of gastrointestinal angiodysplasias and attitudes concerning these practices among Dutch gastroenterologists.

To achieve this aim, a 19-item web-based survey covering current practices in the treatment of gastrointestinal angiodysplasias was administered between February and April of 2015 to gastroenterologists in the Netherlands.

Results: Of the 395 e-mailed questionnaires, a total of 111 (28%) gastroenterologists completed the survey (mean age = 47 years; 24% women), and the sample is representative for the profession in the Netherlands. Respondents correctly identified Von Willebrand disease (17%), chronic kidney disease (21%) and aortic stenosis (86%) as risk factors for the development of angiodysplasias. Colonoscopy (54%) and esophagogastroduodenoscopy (43%) were the preferred first tools to screen for angiodysplasias. The favoured (77%) first treatment option is endoscopic argon plasma coagulation, while 20% starts iron supplementation or blood transfusions. This decision on treatment strategy is mostly (65%) based on the location of the angiodysplasia. Thirteen percent of the gastroenterologists would treat angiodysplasias as a coincident finding during endoscopy for another indication than anaemia. Of the pharmacological therapies, thalidomide (40%) is preferred over octreotide (19%). In case octreotide is prescribed, 20 mg monthly is mostly (52%) given after a test period with short-acting octreotide (86%).

Conclusion: Identification of risk factors, the diagnostic tools used and treatment strategies varies widely between gastroenterologists in the Netherlands. Moreover, a considerable proportion of gastroenterologists would treat angiodysplasias found by coincidence, which is not according to endoscopic guidelines. A guideline for the treatment of angiodysplasias might be helpful to create a more uniform and evidence-based practice.

Disclosure of Interest: None declared

P1219 PROSPECTIVE, QUANTITATIVE ASSESSMENT OF PAIN REDUCTION AND QUALITY OF LIFE IMPROVEMENT FOLLOWING VASCULAR INTERVENTION IN CHRONIC MESENTERIC ISCHEMIA; A PILOT STUDY

L. Everlo¹, J. Kolkman¹², P. Mensink¹, M. Brusse-Keizer³, B. Geelkerken⁴, E. Stassen⁵

¹Gastroenterology, Medisch Spectrum Twente, Enschede, Enschede, ²Gastroenterology, University Medical Centre Groningen, Groningen, ³Medical School Twente, ⁴Vascular Surgery, ⁵Interventional Radiology, Medisch Spectrum Twente, Enschede, Enschede, Netherlands

Contact E-mail Address: l.everlo@mst.nl

Introduction: There is a lack of knowledge of the quantitative effects of treatment of chronic mesenteric ischemia (CMI) on pain and health-related quality of life (HRQOL). This prospective pilot-study was designed to determine the mid-term change of pain intensity and HRQOL in CMI treatment.

Aims & Methods: Patients with mesenteric ischemia, treated with endovascular intervention for luminal stenosis or endoscopic release of the diaphragm crux in celiac artery compression syndrome between August and December 2013 were enrolled. For pain we used the visual analogue scale for pain intensity (VAS-PI, graded 0-100 mm). For HRQOL we used the 36-item Short Form Health Survey (SF-36). All parameters were obtained before and three months after the intervention.

Results: We included 29 patients; mean age 55.9 years (SD 20.0), 79.3 % female. Single-vessel (n=7), multi-vessel (n=15) atherosclerosis and celiac artery compression syndrome (n=7). The VAS for pain improved following treatment: for the average pain from median 60 (IQR: 48 – 72) to 2 (IQR: 0 – 40, p < .001), for postprandial pain from median 74 (IQR: 63–84) to 2 (IQR: 0–40, p < .001), and for post-exercise pain from median 63 (IQR: 50–80) to 4 (IQR: 0–30, p < .001). The number of painful days per week decreased from median 7 days (IQR: 5–7) to 1 day (IQR 0–6.8 days, p < .001). The HRQOL measured with SF-36 improved for five of eight dimensions (role physical (p.005), bodily pain (p.001), vitality (p.004), social functioning (p.001) and mental health (p.001)) and the both component summary scores (physical (p.008) and mental (p.009)).

Conclusion: This pilot study showed that three months after vascular intervention for CMI the pain is significantly reduced and quality of life for patients improved. The magnitude of effects exceeded our expectations, but larger studies with longer follow-up are needed to confirm this observation.

Disclosure of Interest: None declared

TUESDAY, OCTOBER 27, 2015   09:00-17:00

NUTRITION II – HALL 7__________

P1220 EFFECTS OF GUT MICROBIOTA MANIPULATION BY ANTIBIOTICS ON PLASMA AMINO ACID LEVELS IN OBESE HUMANS

E. Neis¹, D. Reijnders², G. Goossens², E. Blaak², C. Dejong³, S. Rensen¹, on behalf of NUTRIM School for Nutrition, Translational Research in Metabolism

¹Surgery, ²Human Biology, Maastricht University, ³Surgery, Maastricht University Medical Center+, Maastricht, Netherlands

Contact E-mail Address: e.neis@maastrichtuniversity.nl

Introduction: Gut bacteria can alter the bioavailability of amino acids and have been implicated in the pathogenesis of metabolic disease. Obesity and type 2 diabetes are associated with elevated systemic concentrations of aromatic and branched-chain amino acids (BCAA).

Aims & Methods: We aimed to investigate the effects of gut microbiota knock-down on arterial amino acid levels in humans. For this, 38 obese male subjects (BMI 31.2 ± 2.6kg/m², age 59 ± 7y, HOMA-IR 4.5 ± 0.2) with impaired fasting glucose and/or impaired glucose tolerance participated in a randomized double-blind placebo-controlled trial. Subjects were orally treated with 1500mg/day amoxicillin (AMOX; broad-spectrum antibiotic), vancomycin (VANCO; aimed at Gram-positive bacteria), or placebo (PLA; microcrystalline cellulose) for 7 days. Before and after treatment, arterial concentrations of 21 amino acids were measured using liquid chromatography.

Results: Baseline BCAA concentrations were high but did not differ between groups: 445.0 ± 35.9µmol/L (VANCO), 423.3 ± 42.7µmol/L (AMOX), and 440.6 ± 44.7µmol/L (PLA), P=0.406. AMOX treatment specifically increased BCAA levels in comparison to PLA (464.3 ± 60.7µmol/L vs. 434.6 ± 66.5µmol/L; P=0.042), whilst VANCO treatment did not (441.9 ± 30.3µmol/L; P=0.867). Within treatment groups, isoleucine (one of the BCAA) concentrations increased significantly upon both AMOX (from 68.4 ± 8.1µmol/L to 79.3 ± 10.9µmol/L; P=0.003) and VANCO treatment (from 70.3 ± 7.7µmol/L to 78.3 ± 9.6µmol/L; P=0.001), but not in the PLA group (from 75.6 ± 10.5µmol/L to 78.1 ± 12.3µmol/L; P=0.305). Besides, arginine concentrations increased significantly only upon AMOX treatment (from 89.9 ± 20.1µmol/L to 101.5 ± 21.2µmol/L; P=0.025). Other amino acids were not affected by any treatment.

Conclusion: The broad-spectrum antibiotic AMOX increases plasma BCAA concentrations. Current ongoing analyses will shed light on the nature of the gut microbiota alterations provoked by AMOX in relation to specific amino acid aberrations, parameters of insulin sensitivity, and substrate metabolism in obese subjects with impaired glucose tolerance.

Disclosure of Interest: None declared

P1221 ADIPOCYTE HYPERTROPHY AND INFLAMMATION COULD AFFECT LIVER INJURY IN NAFLD BY ALTERNATIVE MECHANISMS

J.-P. Sowa¹, M. Schlattjan¹, G. Gerken¹, A. Canbay¹

¹Department for Gastroenterology and Hepatology, University Hospital, University Duisburg-essen, Essen, Germany

Contact E-mail Address: ali.canbay@uni-due.de

Introduction: Lifestyle changes and obesity have spread over the world, leading to an obesity epidemic. Metabolic syndrome (MS) induced by obesity is similarly common in industrialized countries and accordingly non-alcoholic fatty liver disease (NAFLD) and the more severe form non-alcoholic steatohepatitis (NASH) are the most common liver diseases in industrialized countries.

Aims & Methods: Aim of the present study was to investigate if changes in adipose tissue affect development or severity of NAFLD and NASH in MS. To this end visceral adipose tissue, liver tissue samples and blood were obtained from 145 morbidly obese patients (age median = 49 ± 10y; 114w/30m; mean BMI: 53 ± 8.7kg/m²) undergoing bariatric surgery. Biopsies were scored with NAFLD activity score (NAS; median 3/range 1-7) and patients were grouped as NAFL (NAS ≤ 4) or NASH (NAS > 4). Blood samples taken before surgery were analyzed for parameters of liver injury M30 (Apoptosis) and M65 (Overall cell death) and adiponectin. Visceral adipose tissue and hepatic mRNA levels of genes for inflammasome activity and fatty acid metabolism were assessed by qRT PCR.

Results: NASH patients showed significantly higher concentration of markers for cell death (M65), HbA1c, classic liver parameters (ALT, AST), and CRP in serum. Adiponectin serum concentration was significantly lower in NASH. Expressions of analyzed genes did not differ between the groups. Though, NAS was significantly correlated to visceral adipocyte cell size, classic liver parameters, fasting blood glucose and HbA1c, M65, and to liver mRNA expression of MCP1 and NLRP. Cell size of visceral adipocytes was correlated to serum leptin and liver mRNA expression of ATG12 and was inversely correlated to mRNA expression of FASN and CGI-58 in the liver. Moreover MCP1 mRNA expression in adipose tissue correlated with mRNA expression of MCP1, autophagy genes (ATG5, ATG12, LC3), and PPARγ2 in the liver. Expression of the FAS-Receptor in adipose tissue correlated with mRNA expressions of CGI-58 and PPARγ2 in liver tissue.

Conclusion: These results suggest that visceral adipocyte hypertrophy affects hepatic regulation of fatty acid metabolism by downregulation of genes involved in triglyceride breakdown. This may lead to accumulation of lipotoxic compounds and increased liver injury. In contrast high HbA1c might be associated to increased inflammation in the adipose tissue which seems connected to inflammatory gene expression and autophagy in the liver, affecting liver metabolism by other mechanisms.

Disclosure of Interest: None declared

P1222 ACTIVATORS OF THE TRANSCRIPTION FACTOR NRF-2 AS NEW REGULATORS OF HEPCIDIN EXPRESSION

J. Martin¹, S. Ulrich-Rückert¹, J. Stein²

¹Pharmaceutical Chemistry, Goethe University Frankfurt, ²Hospital of Sachsenhausen, Frankfurt a.M., Germany

Contact E-mail Address: martin.julia@gmx.de

Introduction: Hepcidin, an acute phase protein, is regarded as central mediator of the cytokine-induced anaemia of chronic inflammation (ACI), one of the most common causes of iron deficiency anaemia in patients with inflammatory bowel disease and obesity. Identified as primary trigger is the STAT-3 mediated induction of hepcidin synthesis in the liver and macrophages by cytokines of the IL-6 family (IL-6, oncostatin M).

Aims & Methods: The current study aimed to determine additional signal transduction paths of cytokine-induced hepcidine synthesis, with particular focus on a possible role of the transcription factor NF-E2-related factor 2 (Nrf2). HepG2 and Huh7 cells were cultivated in standard conditions and treated for 6 or 16 h with either IL-6 (10 ng/ml) or OSM (10 ng/ml) alone, or in combination with STAT-3 inhibitor (50 µM), sulforaphane (SFN) (10 µM), dimethylfumarat (DMF) (100 µM), 15-Deoxy-Delta-12-14-prostaglandin J2 (15d-PGJ2) (10 µM). For the reporter gene assay, the cells were transfected by lipofectamine with hepcidin promoter plasmid, and the luciferase activity was measured luminometrically. Quantitative real time PCR was performed for quantitative determination of mRNA. Proteins were analysed using western blot.

Results: Both IL-6 (10 ng/ml) and OSM (10 ng/ml) trigger significant hepcidin promotor activation (***p < 0.001), which could be significantly reduced (***p < 0.001) by coincubation with the STAT3 inhibitor (VI, S3I-201). Coincubation of OSM and IL-6 with the Nrf-2 activators SFN (***p < 0.001), DMF (**p < 0.01) and 15d-PGJ2 (*p < 0.05) led not only to significant inhibition of hepcidin promotor activity, but also to a significant reduction of intracellular hepcidin mRNA levels (mind. *p < 0.05). No reduction of the pSTAT/STAT ratio was observed after 8 and 16h incubation with SFN.

Conclusion: The results indicate the transcription factor Nrf-2 to play a role in the expression of the iron regulator hepcidin, with possible involvement of STAT-3 independent signal transduction pathways.

Disclosure of Interest: None declared

P1223 IRREGULAR BOWEL HABIT INCREASES THE RISK OF OBESITY

K. A. Shemerovskii¹², V. I. Ovsiannikov², V. P. Mitreikin¹

¹Pathophysiology, Pavlov I P University, ²Physiology of visceral system, Institute Experimental Medicine, St-Petersburg, Russian Federation

Contact E-mail Address: constshem@yandex.ru

Introduction: Bowel habit in accordance with chronobiology is one of the fundamental circadian rhythms with the regular frequency of at least 7 times a week. The slowing of the rhythm in the form of constipation is a risk factor for colorectal cancer [1,2], the risk of which is increased in obesity [3,4]. However, the impact of the slowdown of the rhythm on the risk of obesity remains poorly studied.

Aims & Methods: The aim of this study was to elucidate the relation between irregular bowel habit and the risk of obesity.

Methods: Validated questionnaires were used for weekly monitoring of circadian rhythm of defecation at 2501 persons, who consider themselves healthy. Regular bowel habit was detected in 1399. Irregular bowel habit was diagnosed in 1102. To diagnose the risk of obesity we randomized two groups of 200 persons with regular and irregular rhythm of defecation. The first group of 100 people (86 women) 23-85 years demonstrated regular bowel habit (daily morning bowel movement with a frequency of 7 times per week). The second group of 100 persons (90 women) 25-79 years demonstrated irregular bowel habit (not daily defecation, frequency 1-6 times per week). The analyzed groups did not significantly differ by gender and age. We calculated the body mass Index (BMI), according to which each group was divided into three subgroups: I – BMI 20-25 kg/ml — normal, II — BMI 25-30 kg/ml— overweight, III — BMI above 30 kg/ml is obesity.

Results: There were identified 53 persons with normal BMI, 37 persons with overweight and 10 subjects with obesity among 100 individuals of the first group with regular bowel habit (RBH). Consequently, in a group of persons with regular bowel habit the risk of obesity was 10%. There were 36 persons with normal BMI, another 36 persons - with overweight, and 28 subjects with obesity among 100 persons of the second group with the irregular bowel habit (IBH). Consequently, in the group of persons with a broken, irregular bowel habit the risk of obesity was 28%. Thus, the risk of obesity among patients with IBH was almost three times (2.8 times) higher than among persons with RBH.

Conclusion: Among individuals with regular bowel habit the probability of normal body mass index (53%) was almost 1,5 times higher than in patients with irregular bowel habit (36%). Among those with irregular bowel habit the risk of obesity (28%) was almost 3 times higher than in those with regular bowel habit (10%). The lack of regular bowel habit predominantly in women of different age significantly (almost 3 times) increases the risk of obesity.

Disclosure of Interest: None declared

P1224 PRELIMINARY RESULTS OF AN ONGOING MULTI-CENTER, PROSPECTIVE, CONTROLLED TRIAL OF THE DUODENAL-JEJUNAL BYPASS LINER FOR THE TREATMENT OF TYPE 2 DIABETES MELLITUS IN OBESE PATIENTS: EFFICACY AND FACTORS PREDICTING A SUB-OPTIMAL EFFECT

M. Benes¹, T. Hucl¹, P. Drastich¹, P. Stirand¹, J. Spicak¹

¹Hepatology and Gastroenterology, Institute of Clinical and Experimental Medicine, Prague, Czech Republic

Contact E-mail Address: marek.benes@ikem.cz

Introduction: The global increase in obesity incidence results in an increase of type 2 diabetes mellitus (T2DM) incidence. Surgical treatment has proven to be effective, however it carries a high risk of complications. The duodenal-jejunal bypass liner (EndoBarrier®, GI Dynamics, DJBL) is an endoscopic implant that mimics the intestinal bypass portion of the Roux-en-Y Bystric Bypass. It results in weight loss and improvements in glucose control in obese patients with T2 diabetes mellitus (T2DM).

Aims & Methods: This is an interim report of an ongoing three years study. The aim of this prospective, controlled, multicentre study is to determine the effectiveness of DJBL and to identify clinical factors associated with a sub-optimal outcome of DJBL.

Results: Fifty seven subjects (32 with an implant, 25 controls) were included in the study. The groups were comparable with respect to age, gender, BMI (mean 40.7 vs. 38.5 kg/m2), T2DM duration (7.3 vs. 8.1 years), HbA1c level (89 vs 83 mmol/mol) and T2DM treatment. In the DJBL group, all devices were successfully implanted. Only four devices had to be explanted prior to the end of the 10 months study period (bleeding, dislocation and need for ERCP because of choledocholithiasis). The mean procedure time was 19.2 minutes for an implantation and 18.5 minutes for an explantation. At 10 months there was significantly greater weight loss and %EWL (21% vs. 8% and 44 vs. 14) and significantly improved long term compensation of T2DM marker HbA1c (decreased by 25 vs. 11 mmol/mol) in the DJBL group. T2DM medicinal treatment could be reduced in more device subjects than controls. There was no serious adverse event. Mild abdominal pain and nausea after implantation were experienced by 72% of patients during first 14 days after implantation, 33% of patients during the first month and 10% of patiens after one month. Lower initial BMI, distal position of the anchor and lower body height were identified as negative prognostic factors for pain.

Conclusion: The DJBL is safe when implanted for 10 months, and results in significant weight loss and HbA1c reduction. This suggests that this novel device is a candidate for the primary therapy of morbid obesity and T2DM. Lower initial BMI, distal position of the anchor and lower body height could be negative prognostic factor for pain.

Disclosure of Interest: None declared

P1225 CD24 POLYMORPHISMS ARE ASSOCIATED WITH OBESITY RISK

N. Shemesh¹, I. Naboichtchikov¹, S. Shapira¹, D. Kazanov¹, S. Zigdon¹, L. Galazan¹, A. Leshno¹, S. Kraus¹, A.-A. Subhi², N. Arber¹

¹Integrated Cancer Prevention Center, ²Department of Surgery, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

Contact E-mail Address: nadira@tlvmc.gov.il

Introduction: Background: Obesity is a global epidemic and major risk factor for various health conditions. It is a multifactorial condition and has genetic and environmental etiology. Several studies have suggested candidate genes that may predispose to obesity. CD24 is a small, mucin-like glycoprotein that is expressed in almost all tumors. We have recently found that CD24 knockout male (but not female) mice are overweight and display greater insulin sensitivity than their wild-type (WT) littermates. Several single nucleotide polymorphisms (SNPs) in the CD24 gene are known to be associated with various cancers and autoimmune diseases.

Aims & Methods

Aim: Evaluate whether CD24 SNPs are associated with risk of obesity.

Methods: Genomic DNA was obtained from peripheral blood leukocytes of 63 obese Israeli patients (BMI ≥ 35; 27 males, 36 females) and 53 age- and gender-matched healthy controls (BMI ≤ 27; 30 males, 23 females). Samples were genotyped for the CD24 SNPs: C170T (rs8734), TG1527del (rs3838646), A1626G (rs1058881) and A1056G (rs1058818) by real-time PCR using Custom TaqMan® SNP allelic discrimination assays. χ² test was used to examine whether the CD24 gene polymorphisms are associated with obesity. An association was considered statistically significant if p< 0.05. Odds ratio (OR) and 95% confidence interval (CI) were estimated by logistic regression models.

Results: A1056G and A1626G SNPs were found to be more prevalent in obese patients than in normal weight subjects (OR=2.973, 95% CI: 1.155-7.6527, p = 0.0234 and OR=4.7212, 95% CI: 2.1408-10.412, p = 0.0001, respectively). Moreover, all four CD24 SNPs carriers were more predominant in the obese group, although the correlations were not statistically significant. In addition, gender adjustment revealed a significant association between A1626G and obese male patients. The prevalence of the WT variant was 0% in the obese males and 76.7% control males (p = 0.0001). A similar trend was found for A1056G, although the correlation was not statistically significant (OR=4, 95% CI:0.9667 -16.551, p = 0.0613).

Conclusion: CD24 may play a role in male obesity

Carriers of A1056G and A1626G CD24 SNPs may be more prone to develop obesity, and in particular male A1626G carriers.

No correlation was found between age-dependency and genetic variant distribution in obese patients.

Disclosure of Interest: None declared

P1226 CERIUM DIOXIDE NANOPARTICLES IN THE NOVEL ANTIOBESITY TREATMENT STRATEGY

O. Virchenko¹, T. Falalyeyeva¹, N. Kobyliak², T. Beregova¹, L. Ostapchenko¹, M. Spivak³

¹Taras Shevchenko National University of Kyiv, Educational and Scientific Centre "Institute of Biology", ²Endocrinology, Bogomolets National Medical University, ³Zabolotny Institute of Microbiology and Virology, Kyiv, Ukraine

Contact E-mail Address: ovirchenko@gmail.com

Introduction: Childhood obesity is a predisposing factor for poor health in adolescence and also in adulthood. The number of overweight has more than doubled in children and quadrupled in adolescents in the past 30 years. Today the correction of lifestyle and diet remain the most effective way of obesity treatment. Despite of this a lot of obese people do not improve their health and the search of nontoxic antiobesity drugs is still urgent.

Aims & Methods: So, the aim of the study was to investigate the influence of cerium dioxide nanoparticles (nCeO₂) intermittent administration on the obesity in rats induced with neonatal injection of monosodium glutamate (MSG).

The study was carried out on 3 groups of rats: control, MSG- and MSG + nCeO₂, 10 animals in each. Just after the born they were injected with saline (control) or MSG (4 mg/g, 3M) at 2^nd–10^th day of life subcutaneously. A month after born MSG-rats had been treated with water in a volume of 2.9 ml/kg, MSG + CeO₂ groups – with 1 mM solution of CeO₂ (1 mg/kg) intragastrically (i.g.). Introduction had been performed intermittently (two-week courses alternated with two-week breaks) for 3 months. In 4-month rats visceral adipose tissue (VAT) mass was measured, content of lipid peroxidation products in serum and enzymatic activity of superoxide dismutase (SOD) and catalase was estimated by standard biochemical methods. The content of proinflammatory cytokines (interleukin (IL)-1β, IL-12Bp40, interferon-γ (INF-γ)) and anti-inflammatory cytokines (IL-4, IL-10, tumor growth factor-β (TGF-β)) were measured by ELISA kits.

Results: In 4-month MSG-rats it was observed the development of visceral obesity in rats that was confirmed by the increase of the VAT mass, alteration of body mass index, index Lee, malfunction of cytokine system and shift to prooxidative processes. In MSG + nCeO₂ we established the decrease of visceral obesity (the VAT mass in MSG-group vs. MSG + nCeO₂ group 19.0 ± 2.0 g vs. 8.3 ± 1.4 g., p < 0.05). nCeO₂ significantly reduced the conjugated dienes content by 27% (p < 0.05), TBA-products – by 43% (p < 0.05) and Schiff bases – by 21% (p < 0.05) compared to MSG-group. Nanoparticles reduce the content of proinflammatory cytokines (IL-1β, IL-12Bp40, INF-γ) in rat serum. We have also performed the preclinical study of nCeO₂ on rat and showed its very low toxicity (LD₅₀ > 2000 mg/kg i.g., V toxicity class).

Conclusion: Thus, it was revealed the antiobesity properties of intermittent administration of nCeO₂. The reduction of visceral adiposity in rats by nCeO₂ was associated with its antioxidant and anti-inflammatory properties. Discovered properties and low toxicity of nCeO₂ allow to recommend it for clinical investigation.

Disclosure of Interest: None declared

P1227 COLONIC BIOMASS: EFFECT OF DIET, MEALS AND DEFECATION

A. Bendezú¹, M. Mego¹, X. Merino², A. Accarino¹, E. Monclus³, M. Izquierdo⁴, I. Navazo⁴, F. Azpiroz¹⁵

¹Digestive System Research Unit, ²Radiology Department, University Hospital Vall d'Hebron, ³Department of Computer Languages and System, ⁴Department of Computer Languages and System, Universidad Politecnica de Cataluña, ⁵Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain

Contact E-mail Address: azpiroz.fernando@gmail.com

Introduction: The metabolic activity of colonic microbiota is influenced by diet and meals, but their effect on colonic biomass is not known. Our aim was to determine whether and to what extent meals and diet influence colonic content.

Aims & Methods: In 10 healthy subjects 2 abdominal MRI scans were acquired during fasting one week apart after 3 days on low- and high-residue diets, respectively. On each diet, daily fecal output and the number of the daytime anal gas evacuations were measured. On the first study day, a second scan was acquired 4 h after a test meal (n=6) or after 4 h without ingesting anything (n=4). On the second study day, a scan after a spontaneous bowel movement was also acquired.

Results: On the low-residue diet, daily fecal output averaged 145 ± 17 mL, subjects passed 11 ± 2 anal gas evacuations during daytime and by the third day colonic content was 622 ± 44 mL. The high-residue diet increased the 3 parameters up to 223 ± 19 mL fecal output, 17 ± 3 anal gas evacuations and 821 ± 59 mL colonic content (p < 0.05 vs low-residue diet for all). On the low-residue diet, 4 hours after the test meal colonic content increased up to 732 ± 51 mL (p < 0.05 vs first fasting scan), whereas no significant change was observed after 4 hours fast. Defecation significantly reduced colonic content in distal colonic segments (by 29 ± 5%; p = 0.002).

Conclusion: Meals and diet influence microbiota metabolic activity and colonic biomass as well.

Disclosure of Interest: A. Bendezú: None declared, M. Mego: None declared, X. Merino: None declared, A. Accarino: None declared, E. Monclus: None declared, M. Izquierdo: None declared, I. Navazo: None declared, F. Azpiroz Financial support for research: Danone, Given, Beneo, Shire, Clasado, Consultancy: Danone, Almirall

P1228 THE INTERACTIONS BETWEEN DIET, MUCOSAL PROLIFERATION AND GI CANCER RISK IN RURAL AFRICANS AND AFRICAN AMERICANS

H. Kaseb¹, K. Mohamed¹, J. Ou¹, S. O Keefe¹

¹Department of Gastroenterology, University of Pittsburgh, Pittsburgh, United States

Contact E-mail Address: phys.hatemosama@inbox.com

Introduction: Based on the analysis of worldwide epidemiological studies, it has been estimated that >90% of GI cancers are diet-related. African Americans have an extremely high risk of colon cancer (∼65:100,000) while rural Africans rarely get the disease. On the other hand, rural Africans have an extremely high risk of squamous cell carcinomas of the esophagus (125/100,000 in men) while African Americans have a low risk.

Aims & Methods: We investigated the usual diets and performed upper and lower endoscopies to obtain mucosal biopsies for the measurement of mucosal biomarkers of cancer risk form the esophagus, stomach, and colon (Ki67 staining of proliferative epithelial cells) in matched groups (n=20, age 50-65, BMI 18.5-35 kg/m2) from each population.

Results: Dietary analyses based on 3-day recalls have shown that there are major differences in the diets of rural Africans when compared to African Americans. Our measurements show that the Ki67 staining of esophageal epithelial proliferative cells was higher in rural Africans than African Americans. The glandular gastric ki67 cell staining was also higher in the rural Africans compared to African Americans. On the other hand, African Americans had higher proportions of Ki 67 staining cells in the colonic mucosal crypts.

Conclusion: Based on our measurements of epithelial proliferation rates by Ki67 immunohistochemistry as a biomarker of cancer risk, our results support the view that the high fiber, low meat and fat African diet suppresses colon cancer risk, but that its lower vitamin and antioxidant content may increase the risk of upper GI cancers as compared to African Americans. The high prevalence of H pylori infections in Africans (i.e. 80%) was associated with higher antral proliferative rates, but not with cancer rates in the population as a whole.

Disclosure of Interest: None declared

P1229 INTAKE OF NATURALLY-OCCURRING OLIGOSACCHARIDES WITH POTENTIAL PREBIOTIC ACTIONS: VALUABLE DATA FOR FUTURE PREBIOTIC RESEARCH

J. Barrett¹, J. Muir¹, P. Gibson¹

¹Gastroenterology, Monash University, Melbourne, Australia

Contact E-mail Address: jacqueline.barrett@monash.edu

Introduction: Reducing intake of indigestible, fermentable, short chain carbohydrates (low FODMAP diet) has recently been shown to reduce absolute and relative abundance of ‘beneficial’ bacterial in the faeces. Furthermore, mildly increasing FODMAP intake over that in the habitual diet had prebiotic effects [1]. These variations are likely to be due to alteration in dietary fructo-oligosaccharides (fructans) and galacto-oligosaccharides (GOS), which, when given as pure supplements at doses of 5-10 g/d can be prebiotic. However, the impact in clinical trials of such prebiotics on clinical outcomes has been in general disappointing. Dietary prebiotic intake has never been taken into account in such studies.

Aims & Methods: The aim of this study is to define the potential influence of normal dietary intake of oligosaccharides by quantifying dietary fructan and GOS intake and examining variance across individuals.

Data obtained during the validation of a food frequency questionnaire in 72 healthy Australians [2] was reanalysed using an updated FODMAP database that included recent publications [3] and unpublished addition. Intakes of fructans and GOS were calculated and expressed as g/d, presented as mean, range and quartiles.

Results: Mean (SD) of fructan and GOS intake was 3.8 (1.1) and 1.2 (0.9) g/d, respectively. Combined prebiotic fructan and GOS intake ranged from 1.4 – 10.3 g/d. Common foods contributing to the higher fructan intake were wheat and rye breads, pasta, onion, garlic and shallots and the most common sources of GOS were legumes and nuts.

Table 1.

Prebiotic Fructan and GOS consumption data from the CNAQ validation study

FODMAP type	Mean (SD) g	Range (g)	1st Quartile (g)	2nd Quartile (g)	3rd Quartile (g)	4th Quartile (g)
Fructan	3.8 (1.1)	1.1-7.3	<2.9	2.9-3.7	3.8-4.6	>4.6
GOS	1.2 (0.9)	0.2-4.3	<0.6	0.6-0.9	1.0-1.4	>1.4
Fructan + GOS	5.0 (1.6)	1.4-10.3	<3.7	3.7-4.8	4.9-6.2	>6.2

Conclusion: Dietary intake of potentially-prebiotic oligosaccharides varies widely from minimal (where effects of supplemented prebiotics may be high) to high (where additional prebiotic effects of supplements are less likely). These findings imply that the highly variable inter-individual effect of supplemental prebiotics in clinical trials might reflect habitual dietary intake, which should be assessed in any prebiotic trial. Such an approach might assist in defining the value or otherwise of prebiotic supplementation.